http://history.amedd.army.mil/booksdocs/korea/blood/chapter20.htm
CHAPTER XX
The Blood, Plasma, and Related Programs in the
Korean War
(from "The Blood Program in World War II")
Part I. Administrative Background
GENERAL CONSIDERATIONS
When the Korean War broke out on 25 June 1950,1 less
than 10 years after the United States had entered World War II and
less than 5 years after that war had ended, the situation was
improved over the situation in December 1941 in only one respect: No
well-organized blood bank system was in operation, but a plan for
the supply of whole blood and plasma did exist. The plan had not
been implemented, however, because it had been prepared only a short
time before the outbreak of hostilities. It is extremely unfortunate
that planning had not begun earlier, for the need for whole blood
arises whenever combat commences; the Korean War proved again that
whole blood cannot be provided promptly and efficiently unless
supplies, equipment, trained personnel, and a detailed plan for its
collection, processing, transportation, and distribution have
already been set up.
When the Korean War broke out, the course of events in respect to
the blood program was as follows:
1. Blood collecting teams were immediately utilized in Japan, to
meet the first need for blood in the field.
2. These supplies proved inadequate as action became more
intense, and requests for whole blood were sent to the Zone of
Interior.
3. The American Red Cross was asked, as in World War II, to
become the collecting agency for blood for the oversea airlift.
Fortunately, this agency already had in operation a blood collecting
program to supply blood to civilian hospitals in the United States,
and could build upon it.
4. Later, when the initial program proved inadequate, an Armed
Forces Blood Program and a National Blood Program were established
and remained in operation until the end of active fighting in Korea.
5. A plasma program was also developed which later had to be
discontinued because of the risk of serum hepatitis associated with
plasma infusions (p. 776). The production of human serum albumin was
substituted for the production of plasma and was supplemented by the
production of plasma expanders (the so-called blood substitutes of
World War II).
1 That date should be borne in
mind. Unless the dates of the various activities to be described
are borne in mind and are related to the dates of the Korean War
(25 June 1950, when the invasion of South Korea occurred, and 27
July 1953, when the armistice was signed), it will not be
realized that, in many instances, the actions were almost too
late.
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In spite of the expedient nature of the blood program, casualties
in Korea never lacked the blood they needed, but the comment is
justified concerning this war, as it was concerning World War II,
that the efficient way to provide blood for combat casualties is not
to wait for the need for it to arise and then to provide it, at
least initially, by a series of improvisations.
It is interesting, and somewhat depressing, to note in various
reports of conferences concerning the blood and blood-derivatives
program in the Korean War how quickly the World War II experience
seemed to have been forgotten and how the tendency was again evident
to concentrate on agents other than whole blood in the management of
combat and other casualties. At a meeting of the Subcommittee on
Shock, Committee on Surgery, NRC (National Research Council), on 14
November 1951 (1), Dr. Walter L. Bloom rather impatiently
called the attention of the members to the fact that the entire
philosophy of plasma expanders was questionable. Military and
surgical groups, he said, should define the limitations of these
substitutes, and they should be considered as suitable for emergency
use only. The first need of combat casualties was for whole blood.
THE INTERIM BETWEEN THE WARS
A knowledge of certain background facts is essential to the story
of the blood, plasma, and plasma-expanders program in the Korean
War, beginning with one major difference between this program and
the similar program in World War II: In the Korean War, the program
covered civilian defense as well as military needs. In World War II,
the two responsibilities were entirely separate. The development of
the program that provided blood and plasma in the Korean War is best
described chronologically.2
1945-46
In September 1945, with the end of hostilities in World War II,
the whole blood program was discontinued immediately, and the plasma
program was terminated as promptly as contracts could be ended. The
research that had been a part of both programs also came to an end
except for the plasma-fractionation studies, which were continued in
Dr. Edwin J. Cohn's laboratory at Harvard.
During the interim between the wars, needs for whole blood in
Army hospitals were met within the hospitals. There were no plans,
militarily or otherwise, to stockpile reserves of plasma for a
national emergency. Indeed, had such a disaster occurred, there
would have been no program to put into effect. The whole blood
program would have died between the wars except for the stimulus
provided by the activities of the American Red Cross.
2 Unless otherwise indicated, the
data in this section of this chapter are derived from the
excellent and well-documented account of the blood, blood
derivatives, and plasma-expanders program in the first 2 years
of the Korean War prepared by Col. Patrick H. Hoey, MC, USAF,
Chairman of the blood and blood derivatives group (2),
and the convenient account of the historical development of the
Office of Assistant Secretary of Defense (Health and Medical)
prepared by Miss Elsie LaMantia (3).
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1947
Postwar activities in respect to blood began on 26 July 1947,
with the passage of the National Security Act (Public Law No. 253,
80th Congress), which established the Department of Defense (2).
This act provided for the establishment of NSRB (National Security
Resources Board) to advise President Harry S. Truman on policies
relating to industrial and civilian mobilization. It also provided
for the policy just mentioned, the integration of civilian and
military health resources. Finally, it authorized steps leading
toward a more unified control of national medical services.
1948
On 1 January 1948, the then Secretary of Defense, Mr. James V.
Forrestal, appointed a Committee on Medical and Hospital Services of
the Armed Forces, to study all questions of common interest to the
three medical services, with a view to obtaining maximum efficiency
and economy in all their operations. Secretary Forrestal's committee
consisted of Maj. Gen. Paul R. Hawley (Ret.), chairman (hence, the
Hawley Committee); the Surgeons General of the Army, the Navy, and
the Air Force; and Rear Adm. Joel T. Boone, MC, USN, who served as
executive secretary.
In the meantime, the President had appointed a Commission on
Reorganization of the Executive Branch of Government under
Ex-President Herbert Hoover (the Hoover Commission), which, by the
middle of 1948, had two task forces working on the coordination of
health and medical matters in the National Military Establishment:
1. The Task Force on National Security (the Eberstadt
Committee).
2. The Task Force on Federal Medical Services (the Voorhees
Committee).
The Hawley Committee had recommended that a civilian committee be
established, to serve in a consultant and advisory capacity to the
Secretary of Defense on medical and health affairs, and both of
these task forces made similar recommendations.
On 9 November 1948, still another committee was appointed, the
Armed Forces Medical Advisory Committee. Its chairman, Mr. Charles
P. Cooper (hence, the Cooper Committee), also served as Deputy to
the Secretary of Defense in the fields of medicine and health. The
committee consisted of the Surgeons General of the three services,
General Hawley, and a number of distinguished civilian physicians.
The recommendations of this committee immediately identified a
structural weakness in the Office of the Secretary of Defense: There
was no agency or personnel in it to implement committee
recommendations after the Secretary had approved them. The Surgeons
General, who were members of the committee, were in the untenable
position of making recommendations to the Secretary and then
receiving these same recommendations from him for comment. This
phase of the problem was solved by removing the Surgeons General
from membership on the Cooper Committee.
1949
In February 1949, the Joint Chiefs of Staff asked that the Cooper
Committee consider the entire question of "unification or
coordination" of the Armed Forces medical services, including the
possible development of a single medical service. At the end of 2
months of intensive study, the committee recommended against a
single Tri-Force medical service. Instead, it recommended that the
recommendations of the Eberstadt, Voorhees, and Hawley Committees
should be implemented and that an organization be established in the
Office of the Secretary of Defense, with authority to act on
committee and other recommendations.
In accordance with this recommendation, the Medical Service
Division was set up in the Office of the Secretary of Defense in May
1949, with a director who had authority to
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establish general policies for the medical services of all three
Armed Forces. The Hawley Committee was then dissolved and its
subcommittees were transferred to the Medical Service Division. The
Cooper Committee continued to function.
On 29 September 1949, the Medical Service Division was renamed
the Office of Medical Services. Its current director, Dr. Richard L.
Meiling, was named Director of Medical Services and Assistant to the
Secretary of Defense for Medical Affairs. Dr. Meiling established a
Medical Advisory Council consisting of the three Surgeons General,
who met weekly in his office. After the Korean War broke out, the
Surgeon General of the U.S. Public Health Service and the Medical
Director of the Veterans' Administration were added to the
membership of the Council.
1951
The Cooper Committee continued to function throughout 1950, as
did the Office of Medical Services. On 2 January 1951, the Cooper
Committee and the Office of Medical Services were replaced by an
Armed Forces Medical Policy Council, whose director was named
Assistant to the Secretary of Defense for Health Affairs. The
Council consisted of the three Surgeons General; a dental surgeon;
and two other civilians, Dr. Isidor S. Ravdin and Dr. W. Randolph
Lovelace III, both of whom had had wide medicomilitary experience.
With the establishment of this council, there was now fully carried
out, for the first time, the intent of Congress as expressed in the
National Security Act of 1947 (p. 715). Also for tile first time:
1. There existed in the DOD (Department of Defense) an
organization with authority to coordinate medical policy within the
department as well as between the department and other governmental
agencies and civilian medical and allied health organizations.
2. The three Surgeons General had authority to represent their
respective departments in the formulation of medical and health
policies at the level of the Department of Defense.
1953
There were no further changes of consequence in the medical
structure of the Department of Defense until 1 April 1953, when DOD
Directive 5136.4 established the position of Assistant to the
Secretary of Defense (Health and Medical) in the Office of the
Secretary of Defense. This was a considerable forward step. All
medical and health policies, plans, standards, criteria, and other
aspects of medical service could now be reviewed in the Office of
the Assistant to the Secretary of Defense (Health and Medical), who
also maintained liaison, on both a national and an international
basis, with all other governmental and civilian health and medical
agencies and associations. The advice of the Surgeons General was
made available to the Assistant to the Secretary of Defense as
necessary.
On 30 June 1953, Congress approved Reorganization Plan No. 6 for
the Department of Defense. This plan authorized, among nine
Assistant Secretaries of Defense, an Assistant Secretary of Defense
(Health and Medical); thus, in effect, regularizing and giving
authority to the plan adopted in the Office of the Secretary of
Defense in April 1953. On 2 September 1953, the Secretary of
Defense, by DOD Directive 5136.4, established a Health and Medical
Advisory Council composed of civilians.
Meantime, the NSRB chairman, former Secretary of the Air Force W.
Stuart Symington, had set up a Health Resources Office, which
reported directly to him and which was responsible for the
development of plans and recommendations relative to mobilization
and allocation of health resources and for the medical aspects of
civilian defense. Dr. Howard A. Rusk was appointed chairman of the
special committee to advise Mr. Symington on broad policies relating
to health resources. When these last actions were taken, the
armistice of 27 July 1953 had already ended the fighting in the
Korean War.
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Comment
The organizational steps just outlined were all extremely
important and are entirely relevant to the blood program in the
Korean War. They meant that, for the first time, the Department of
Defense would coordinate and integrate all phases of its health
program, including the blood program, to with broad policies
established at the presidential level. It also meant that
recommendations of task groups concerning coordination with other
agencies would no longer be conflicting, since both military and
civilian national health agencies would now act jointly, to meet the
overall requirements of national mobilization.
INITIAL STEPS IN THE NATIONAL BLOOD
PROCUREMENT PROGRAM
One of the joint problems that came to the attention of the
Director of Medical Services, Office of the Secretary of Defense, in
1949, soon after the establishment of his position, concerned
military and civilian requirements for whole blood and blood
derivatives. An inventory of existing stocks of plasma and other
derivatives, early in October of that year, indicated that they were
very low (p. 772); that there was no coordinated plan to expand
them; and that, if an emergency should arise, there were no
facilities for their augmentation. Only four laboratories were
producing plasma commercially. Their combined annual production was
about 300,000 units, and they had no incentive to expand it, for
plasma was a nonprofit item.
This situation was viewed with the seriousness it deserved, and,
on 26 October 1949 the Director of Medical Services, acting for the
Secretary of Defense, appointed a task group to study the whole
problem of providing blood, blood derivatives, and plasma
substitutes (expanders) for the Armed Forces in peacetime and in
war. The investigation was to cover such related matters as supplies
and equipment for transfusion; training of personnel in the
technical aspects of procurement, control, storage, transportation,
and use of blood and blood derivatives to meet expanded requirements
of an emergency program; and the development of a system of
logistics capable of meeting requirements on a global scale (4).
The members of this Task Group included Capt. Hilton W. Rose, MC,
USN; Capt. Lloyd R. Newhouser, MC, USN; Col. William S. Stone, MC,
USA; and Lt. Col. (later Col.) Alonzo A. Towner, Jr., MC, USAF. The
comprehensive report which they submitted to the Secretary of
Defense on 15 March 1950 (4) had been approved by the Military
Medical Advisory Council (the predecessor of the Armed Forces
Medical Policy Council) on 14 February 1950. On 5 May 1950, the
report was approved by the Secretary of Defense, in a memorandum
addressed to the three Service secretaries, and thus became official
DOD policy (5).
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As of this date, the retrenchment that had characterized all
activities relating to blood in the postwar period began to be
reversed, but it was almost too late: It was less than 2 months
later that the outbreak of hostilities in Korea required the
immediate translation of still theoretical concepts of a national
emergency into a stern reality, though, fortunately, several
additional weeks were to elapse before a request for whole blood
carne to the Zone of Interior from the combat area.
REPORT OF TASK GROUP
The report by the Task Group to the Director of Medical Services
on "A Suggested Program of Whole Blood and Blood Derivatives for the
Armed Forces" in March 1950 analyzed the problem; summarized the
commercial potential for dried plasma; and outlined the requirements
for stockpiling plasma and for the collection, distribution, and use
of whole blood. In substance, the report was as follows:
The Problem
Whole human blood, required in modern therapy, cannot be
stockpiled because it is extremely labile; it requires constant
refrigeration and precise technical control and handling; and, under
present procedures, it cannot be stockpiled for more than 30 days.
The Armed Forces can operate blood banks to meet peacetime
requirements but cannot supply wartime necessities. It is not
desirable to use combat troops as donors. Neither in peacetime nor
in war can the Armed Forces provide blood derivatives.
The reserves of blood derivatives left from World War II will
largely be outdated by the end of 1950, though some can be
reprocessed, at about a third of the cost of new products. The total
amount that has been reprocessed, however, will provide only a third
to a half of the required war reserve (set at a million units) for
the Armed Forces. Reprocessing and handling can be carried out only
by specially trained personnel, with considerable technical
background.
The present civilian program for blood and blood derivatives is
not adequately organized or planned to meet the requirements of the
Armed Forces, the civil defense program, and other civilian needs in
time of war.
The wartime needs can therefore be met only by a national
program, which must be organized in peacetime.
The Present Situation
At this time (March 1950), the blood procurement situation in
tile United States is as follows:
1. Twenty-one blood banks are in operation in Armed Forces
installations. All have standardized equipment and supplies, are
centrally controlled, and would be capable of
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operating under wartime conditions. Four of these banks are each
collecting 300 pints a month. The others are collecting from 50 to
250 pints each.
2. Some two or three thousand nonprofit blood banks are in
operation, most of which belong to the American Association of Blood
Banks.3 About half of these banks actually draw and
process blood. The remainder, whose chief function is to serve their
own hospitals and adjacent rural communities, act merely as storage
and issue points for blood drawn elsewhere. When the operations of
these banks are entirely intrastate, they are under no control and
their equipment, supplies, and procedures are not standardized. If,
however, these hospital banks would adopt NIH (National Institutes
of Health) standards and could produce significant surpluses above
their own needs, they could contribute to the national blood
program.
3. Four commercial blood banks are in operation in New York.
Others are in operation in Dallas, San Francisco, and Chicago, and
there are a few smaller banks in other locations. They lack trained
personnel and uniform standards, and it is doubtful that they could
expand significantly in time of war.
4. Only three commercial biologic laboratories are now collecting
blood for plasma: Cutter Laboratories, 100,000 pints per year;
Hyland Laboratories, 40,000 pints per year; and Sharp & Dohme,
150,000 pints per year. All these laboratories produced plasma
during World War II, and Sharp & Dohme also produced plasma
fractions, which only Cutter Laboratories is now producing.
Equipment can be manufactured by a number of larger firms as well
as some smaller firms, on reasonably short notice, with certain
exceptions. There would be difficulty, for instance, supplying 15-
to 20-gage needles for intravenous and donor sets if they should be
required at once, though within 6 months, well over a million could
easily be produced.
Recommendations
The Task Group, on the basis of the World War II experience
factor, set the replacement requirements for each combat casualty
who survived to be hospitalized at one 500-cc. unit of whole blood
and the same amount of plasma or other blood-derivative. Only group
0 blood would be used, preserved in ACD (acid-citrate-dextrose)
solution; typed for the Rh factor; and refrigerated at 4° to 10° C.
from collection until administration.
The Task Group did not think that the Department of Defense of
itself could procure such amounts of blood and blood derivatives and
therefore recommended immediate coordination with other interested
governmental and non-governmental agencies in the development of a
program that would meet the standards and fulfill the requirements
of the Department of Defense, as well as civilian requirements, in
peacetime and in wartime.
The Task Group also recommended that the Department of Defense
assume responsibility for the direction and implementation of the
whole blood program and its coordination with other agencies,
including the American Red Cross; Armed Forces blood banks;
commercial biologic agencies; and nonprofit and commercial blood
banks. It was noted that, if these various separate groups were to
serve as an integrated national blood group, they must be tightly
controlled because of the multiple risks attending the use of blood,
including its perishability; incompatibility; possible errors in
grouping, typing, and cross-
3 Although this is the figure used
by the Task Group, it seems high unless every hospital
laboratory storing a few pints of blood is considered a blood
bank.
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matching; contamination from unsound techniques; unsatisfactory
conditions of storage; and possible transmission of such diseases as
malaria, syphilis, and hepatitis.
Finally, the Task Group recommended that the Director of Medical
Services should be responsible for, and direct, the continued study
and implementation of the Department of Defense blood program and
till coordination of tile activities of tile department with those
of other agencies.
In addition to these basic recommendations, the Task Group made
tile following specific recommendations:
1. That transfusion supplies, equipment and procedures as
standardized for the Armed Forces be standardized by all
participating agencies, with the Director of Medical Services, DOD,
taking the necessary steps to accomplish this objective.
2. That biologic standards for blood and blood derivatives be
uniform throughout the country, with necessary legislation to assure
the adoption of the desired criteria.
3. That all military combat plans include logistic requirements
for blood.
4. That all blood donations be voluntary.
5. That a war reserve be established for plasma, plasma
substitutes (expanders), and transfusion supplies and equipment,
with economical maintenance of estimated requirements, and that a
system be devised for replacing deteriorated supplies, so as to
maintain a satisfactory and economical reserve.
6. That research on blood preservation and on improvement of
transfusion equipment be emphasized by the Department of Defense. It
was suggested that the sum of $100,000 be allocated annually for the
next 2 or 3 years to provide for additional research in these
fields.
It was essential, the report of the Task Group concluded, that
the agency for civilian and military whole blood requirements that
was developed in peacetime should be of such a character that it
could be expanded in time of war to meet logistic requirements and
organization, training, and operating procedures. Such an agency
should have ramifications down to the community level, so that, in
an emergency, all potential sources of blood could be tapped. Also,
the personnel of such an agency should be so organized and trained
that, in time of war, its existing operational activities would
simply have to be expanded.
Continuing misconception of requirements for whole blood.-
Another depressing phase of the development of the blood program
after World War II was the position taken by the Director of
Military Supply and the Acting Chief, Requirements Coordination,
Munitions Board, in April 1950, in connection with the
recommendations of the Task Force (6).
Both granted the necessity for a national blood program, the
importance of its prompt development, and the wisdom of correlating
military and civilian requirements, policies, standards, and
procedures. These officers, however, could not agree with the
recommendation that the Director of Medical Services, Department of
Defense, be responsible for, and direct continued study and
implementation of, the DOD blood program and its coordination with
other agencies. Nor could they agree that the director should take
steps to accomplish standardization of related military and civilian
supplies, equipment, and procedures, for the following reasons:
1. Blood and blood derivatives are considered a supply commodity
or munition.
2. The Munitions Board is legally responsible for developing
coordinated policies relating to military supplies.
721
3. The blood program is no different from other programs and must
be handled in the same manner as other programs.
It would be hard to imagine a more total misconception of the
requirements and implications of a whole blood program. The position
of these officers, obviously taken in complete ignorance of how
whole blood must be procured, handled, and administered, represented
everything the Subcommittee on Blood Substitutes, NRC, the Blood
Transfusion Branch, Office of The Surgeon General and other agencies
and personnel had fought against during World War II. Had these
ideas been permitted to prevail, the entire whole blood program for
Korea would have foundered and many lives would probably have been
lost from the use of incorrectly handled blood. The controversy had
no chance to develop, however, for the Secretary of Defense, in
August 1950, gave the operational responsibility of the blood
program to the Directorate, Armed Services Medical Procurement
Agency, and directed the Director of Medical Services, DOD, to
prescribe the policies and standards for the implementation of the
program (7).
IMPLEMENTATION OF TASK GROUP PROPOSALS
In May 1950, Dr. Meiling assumed the chairmanship of a Blood and
Blood Derivatives Committee in the Department of Defense, which had
the function of determining the need of the Armed Services for
plasma and whole blood. He at once appointed an ad hoc committee on
blood and blood derivatives to serve in an advisory capacity to him.
At its meeting on 28 July 1950- a month after the outbreak of the
Korean War- the Military Medical Advisory Group, in a full
discussion of the Blood and Blood Derivatives Program, decided that
the American Red Cross should be the coordinating blood procurement
agency for the Department of Defense and that the Armed Services
Medical Procurement Agency should be assigned operational
responsibility for the program in the Department of Defense.
A week later, when the Secretary of Defense formally assigned
operational and technical responsibility for the program to the
Directorate of the Armed Services Medical Procurement Agency, the
directorate at once requested the chief of this agency to establish
a blood and blood derivatives division within the agency. At the
same time, the directorate requested that the director of Medical
Services, Office of the Secretary of Defense, grant membership in
the Task Group studying the Whole Blood and Blood Derivatives
Program to the chief of the Procurement Agency and the chief of its
Blood and Blood Derivatives Division.
All of these requests were granted. Col. Douglas B. Kendrick, MC,
who had been in charge of the Army blood program in World War II
from its inception until November 1944, was named chairman of the
Blood and Blood Derivatives Group, which position he held for the
next 2 years. On 1 May 1952, he was succeeded by Col. Patrick H.
Hoey, MC, USAF, who held this position
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CHART 11.-Structural organization of blood and
blood derivatives program, 1949
until the end of the war. Lt. Col. Arthur J. Carbonnell, MC, was
the Army member of the group from 15 February 1951 to 18 February
1952.
On 12 September 1950, the Armed Services Blood and Blood
Derivatives Division (which became the Armed Services Blood and
Blood Derivatives Group a few days later) was officially
established. It consisted of a professional staff and of
administrative, field, laboratory, and liaison branches. Its mission
was as follows:
1. To provide whole blood for FECOM (Far East Command).
723
CHART 12.-Structural organization of blood and
blood derivatives program, 1950
2. To provide whole blood for the production of dried plasma for
the DOD War Reserve stockpile.
3. To reprocess outdated stocks of plasma produced in World War
II.
4. To investigate developments in the field of plasma-expanders.
The actual division of responsibility for the blood and plasma
program was that the Committee on Blood and Blood Derivatives
recommended policy and the Blood and Blood Derivatives Group had the
operational responsibility for its implementation.
The structural evolution of the blood and blood derivatives
program in the Department of Defense between 1949 and 1953 is shown
in charts 11, 12, and 13.
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CHART 13.-Structural organization of blood and
blood derivatives program, 1952
NATIONAL RESEARCH COUNCIL
Organization and Functions
The Subcommittee on Blood Substitutes, Committee on Shock,
Division of Medical Sciences, NRC, had done such important work on
the collection and distribution of whole blood and its derivatives,
and had supervised so much valuable research, in World War II, that
it was reactivated in 1948 as the Committee on Blood and Blood
Derivatives. The work of the subcommittee had lapsed at the end of
World War II, but in the interim before its reconstitution, the
American Red Cross, which was entrusted with returning surplus
725
blood derivatives to the people of the United States who had
contributed them, used many of the same physicians who had served on
the subcommittee on its own Committee on Blood and Blood
Derivatives, thus maintaining their contacts with the blood program.
The reason for the reactivation of the World War II subcommittee was
the realization that a national emergency would demand huge amounts
of blood and blood derivatives for civilian as well as military
uses, and the subcommittee was promptly enlarged because of the
complexity of the problems to be solved.
As soon as it was activated, the Committee on Blood and Blood
Derivatives went actively to work. At its first meetings, the stage
of existing knowledge in the special fields of blood and blood
derivatives was assessed. Ad hoc responsibilities were delegated to
particular members, who were directed to investigate equipment,
preservatives, and sterilization of blood and blood derivatives.
Contracts for research in the field of blood and blood derivatives
were reviewed for the National Military Establishment and the
Veterans' Administration.
At the meeting of the Committee on Blood and Blood Derivatives on
3 December 1949, much of the agenda concerned general principles and
policies (8). Dr. Charles A. Janeway, chairman of the
committee, pointed out that the blood program was an integral part
of national defense and that the counterpart of this committee
during World War II had sat as an advisory group to all agencies and
organizations concerned in any way with blood. Its successor
committee would perform the same functions.
Dr. Meiling, Director of Medical Services, Office of the
Secretary of Defense, explained the functions of his office. Dr.
Cohn spoke of the importance of the cooperation of all agencies
concerned in the blood program. During World War II, he noted, no
decision regarding blood products was ever made without the approval
of the Laboratory of Biologics Control, National Institutes of
Health. Many of these matters were within the province of the Food
and Drug Administration. The World War II subcommittee had been
careful never to recommend any action or procedure on the basis of
research alone; the practicability of all recommendations was tested
by pilot operations. It was possible that blood might be collected
by some agency other than the Red Cross, which was now operating
with no obligations to turn over any material to the Armed Forces in
an emergency. The important consideration was that there must be a
single blood program, cooperative and not competitive. In
conclusion, said Dr. Cohn, "Failure to act until an emergency
entails accepting the responsibility for being unprepared."
By this time (December 1949), a great many problems had already
been referred to the Committee on Blood and Blood Derivatives, NRC,
and many more were to be referred to it before and during the Korean
War. The recommendations made concerning them are discussed under
appropriate headings. The contribution of the committee was
incalculable. There were, however, many perfectionists on it, and,
at intervals, the more practical-minded members felt constrained to
remind them of current needs. If, for
726
instance, excessive and unnecessary standards of accuracy were
required, the volume of production would be impractically small. The
point at issue was the quick determination of what agents were safe
to put into people's veins from the standpoint of immediate or
delayed antigenicity and toxicity.
At the December 1949 meeting, an ad hoc committee was appointed
to consider all phases of the blood program, talk with civilian
defense planning groups and other agencies, and then make
recommendations to the Committee. The membership of this committee
included Dr. Janeway, Dr. Cohn, Dr. Ravdin, Dr. Carl V. Moore, and
Dr. Charles A. Doan.
At this same meeting, a number of changes were recommended in the
13 May 1943 agreement with the American Red Cross, both to bring the
text into agreement with the current organizational situation and to
indicate that collections of blood were for civilian needs as well
as for needs of the Armed Forces. It was also recommended that a
committee be formed to serve in an advisory capacity to the American
Red Cross, Department of Defense, National Institutes of Health,
Veterans' Administration, Atomic Energy Commission, and whatever
agency would be responsible for civilian defense.
Some of the problems referred to the Committee on Blood and Blood
Substitutes, NRC, might be mentioned here, to indicate their range
and importance:
1. Could not a preservative solution be
devised in which blood for transfusion and blood intended for
plasma could both be collected?
2. What measures should be adopted to safeguard
plasma to be stockpiled while it was being processed?
3. How could transmission of virus infections
from plasma infusions be prevented?
4. Could the dating period of blood be extended?
5. How could the incidence of clots in collected
blood be reduced?
6. Would siliconing the inside of collecting
bottles improve the product?
7. What was the present estimate of the value of
gelatin? Oxypolygelatin? Dextran? Periston? Inquiries concerning
these and other plasma-expanders were to come up repeatedly.
THE AMERICAN RED CROSS PARTICIPATION
The Committee on Blood and Blood Derivatives, DOD, recommended to
the Secretary of Defense on 2 October 1948 and 10 January, and 13
February 1949 that the American Red Cross be officially designated
as the agency to collect blood for the National Military
Establishment. The Subcommittee on Burns, Committee on Surgery, NRC,
also recommended, in November 1949, that some large-scale machinery
for the collection of blood be set up.
On 20 July 1950, the Secretary of Defense, then Mr. Louis
Johnson, recommended to the Chairman of the American Red Cross, then
Gen. George C. Marshall, that the relation which had existed during
World War II between that organization and the War and Navy
Departments be reestablished between it and the Department of
Defense to meet the needs of the Armed Forces for blood and blood
derivatives (9). On 22 July, General Marshall replied that
the Red Cross would at once increase its blood collections and that
Adm.
727
Ross T McIntire, MC, USN (Ret.), who was assigned to the Red
Cross National Blood Program, would be assigned to work with Dr.
Meiling on the necessary plans (10).
On 30 August 1950, Mr. Symington, as Chairman, NSRB, formally
requested, through General Marshall, that the American Red Cross
accept the responsibility for coordinating a nationwide civil
defense blood program for recruitment of donors and for the
collection, storage, processing, and preparation for shipment of
blood and blood derivatives collected under the program (11).
On 7 September 1950, General Marshall replied that the Red Cross
would accept the specified responsibilities, on the assumption that
local civil defense units would coordinate their planning with the
national program (12).
The Boston Agreement.- Meantime, on 11 and 12 July 1950, the
Committee on Blood and Blood Derivatives, American Red Cross, and
the Red Cross Medical Advisory Committee on the National Blood
Program met in Boston with representatives of the American Medical
Association, the American Association of Blood Banks, and the
American Hospital Association, to determine their relations with
each other. The so-called Boston Agreement provided that these four
agencies would cooperate with each other in peacetime and with the
National Security Resources Board in time of war (13). In
peacetime, there would be a free exchange of blood on a
unit-for-unit basis, as would best serve community needs. As a
matter of principle, surplus blood would be given to the Red Cross
or other designated agencies for conversion into blood derivatives.
In time of war, procurement agencies would be set up in communities
not already served by Red Cross regional blood centers.
It was recognized at this conference that standardization of
equipment for the blood program was desirable in peacetime and
imperative in a national emergency. It was also recommended that all
blood banks cooperating in the joint program should meet the minimum
standards of the National Institutes of Health.
Part II. The Whole Blood Program
Section I. Blood Procurement
in Japan
INITIATION OF PROGRAM
The blood program for the Korean War began in Japan. Here, in the
interim between the wars, a few Army hospitals, all of which were
authorized to provide definitive surgical care, collected blood from
donor lists in accordance with Army Regulations No. 40-1715. These
hospitals, located mainly in the Tokyo and Osaka areas, operated
small banks, sufficient for their own needs.
Within 10 days after the outbreak of the Korean War (then
considered only a police action), it became apparent that the Armed
Forces in combat would
728
FIGURE 167.-Blood donors (Flag allowance personnel,
Commander, U.S. Naval Forces, Far East) lined up outside 406th
Medical General Laboratory blood bank, Tokyo, July 1950, ready to
donate blood for fighting forces in Korea.
require blood in large amounts, and plans were at once made for a
centrally controlled blood procurement program in Japan (2, 14).
Three initial steps were taken:
1. A special blood bank unit was formed from
personnel of the 406th Medical General Laboratory to operate a
blood bank there. As the bank was first set up, it consisted of
a collecting and processing center in Tokyo, a transportation
and courier center (later called the Blood Bank Storage Depot
and Shipping Section) in Tokyo, and an advance blood bank depot
at the 118th Station Hospital in Fukuoka.
2. 8090th Blood Bank Laboratory Detachment
was organized as a temporary duty unit in August 1950 and was
assigned to the 406th Medical General Laboratory. The detachment
consisted of two mobile bleeding units and a laboratory unit. It
functioned until 5 November 1951, when it was replaced by the
48th Blood Bank Laboratory Detachment.
3. Blood bank sections were activated in
Korea, as organic parts of medical supply depots.
The necessary organizational steps were taken quickly, donors
were recruited (fig. 167), and the first shipment of blood from
Japan (69 bottles) was sent to the 8054th Evacuation Hospital in
Pusan, Korea, on the night of 7 July 1950.
729
SUBSEQUENT DEVELOPMENTS
For the first 5 weeks, the blood bank operated on an emergency
basis, as troop strength built up rapidly and field medical
installations were sent to Korea to care for casualties. It then
became evident that the combat in which the U.S. troops were engaged
would be considerably more than a local engagement, rapidly
terminated, and that blood bank operations must be put on a firmer
basis.
The first step was to determine a working ratio between
anticipated casualties and future needs for whole blood. By the use
of figures supplied by the Assistant Chief of Staff, G-1
(personnel), which were available daily and were regarded as
accurate, a ratio was developed of 0.82 pint of blood to each
casualty wounded in action and surviving to be hospitalized.
At this time, the donor panels in the Tokyo-Yokohama areas could
supply, at the most, 100 pints of blood per day. Official approval
had not yet been obtained for the use of Japanese donors, and, until
the end of 1950, blood was secured only from noncombatant Army,
Navy, and Air Force personnel; Allied Forces personnel; civilian
employees of the U.S. Armed Forces; foreign nationals other than
Japanese; and adult dependents of these groups.
When the needs of anticipated casualties were surveyed
realistically, it was at once clear that available local donors
could not possibly meet their requirements, and a request for blood
was made on 15 August 1950 to the Zone of Interior (15) and
promptly acceded to (p. 713). It was hoped, however, that local
sources could continue to meet emergency needs and could also supply
group-specific and Rh-specific bloods, which, as in World War II,
would not be sent from the Zone of Interior.
After 6 months of combat, and after blood from the Zone of
Interior had been reaching Korea for over 4 months, it was found
that the ratio of blood to casualties had undergone a change. The
factor then used, 3.32 pints of blood for each combat casualty who
was hospitalized, was based on an experience factor for logistic
blood requirements that included not only the blood actually used
but the blood wasted in storage and distribution, a wastage that was
then considered unavoidable in such a perishable product as blood in
such combat circumstances as Korea.
The first bloods collected in Japan were transported from the
bank at the 406th Medical General Laboratory to the advance depot at
the 118th Station Hospital in Fukuoka in railway baggage cars, three
of which had been equipped with reach-in reefers (refrigerators) for
this purpose. Later, air transport was used almost exclusively (p.
752).
JAPANESE DONORS
Techniques of collection of blood in Japan generally followed
those employed in Red Cross bleeding centers in World War II until
donations from Japanese began to be accepted, at the end of 1950.
Then, certain changes in
730
procedure were necessary. For one thing, language difficulties
made it necessary to employ a small Japanese staff, as well as to
use nurses and volunteers supplied by the Japanese Red Cross (fig.
168). For another, Japanese medical authorities were at first
reluctant to depart from their standard practice of limiting
donations to 200 cc. Some concessions, naturally, had to be made to
the small size of the Japanese, who could not routinely give 500 cc.
of blood as did U.S. donors, and tables of maximum collections for
bleeding them and others of similar stature were therefore worked
out (table 34). When these standards were adhered to, there was
never any evidence of immediate or delayed harmful effects from the
donations.
TABLE 34. - Authorized collection of
blood, from Japanese nationals and other donors of small stature
[Per pound of body weight]
|
Body weight |
Authorized collection |
Blood and anticoagulant |
|
Male |
Female |
Male |
Female |
Male |
Female |
|
Pounds |
Pounds |
cc. |
cc. |
cc. |
cc. |
|
100 |
105 |
250 |
230 |
370 |
350 |
|
105 |
110 |
260 |
240 |
380 |
360 |
|
110 |
115 |
275 |
250 |
395 |
370 |
|
115 |
120 |
290 |
260 |
410 |
380 |
|
120 |
125 |
300 |
275 |
420 |
395 |
|
125 |
130 |
310 |
285 |
430 |
405 |
|
130 |
135 |
325 |
295 |
445 |
415 |
|
135 |
140 |
330 |
310 |
450 |
430 |
|
Over |
145 |
Maximum |
320 |
Maximum |
440 |
|
--- |
150 |
--- |
330 |
--- |
450 |
|
--- |
Over |
--- |
Maximum |
--- |
Maximum |
PUBLICITY
Publicity for the blood program in, Japan was provided by the
U.S. and the Japanese Red Cross, the Armed Forces radio station in
Tokyo, the Pacific edition of the Stars and Stripes, and similar
sources. Documentary films showing blood bank operations were made
by the Army Signal Corps and by Japanese photographers for use
locally as well as in the United States. Posters, pictures, and
stories were provided for both local and stateside release by
General Headquarters and Joint Logistical Command Public Information
Offices.
On one occasion, a spectacular air rendezvous was made with the
U.S.S. Boxer, then in Korean waters; her crew donated 2,407 pints of
blood in 4 days. On another occasion, Gen. Douglas MacArthur
publicly received a token
731
FIGURE 168.-Japanese mothers, representing the United
Nations Educational, Scientific and Cultural Organization, giving
blood for forces in Korea at 406th Medical General Laboratory,
Tokyo, February 1952, as their children watch.
shipment of blood from the German employees of a commercial
airline. On 4 July 1951, the medical section of the Joint Logistical
Command, at a carnival at Meiji Park, staged a complete
demonstration of blood bank operations; the processing of the blood
was carried out in full view of the spectators. The Gallon Club,
instituted in August 1951, had almost 150 members within a few
weeks.
STATISTICAL DATA
During fiscal year 1951, a total of 43,479 donors were
interviewed at the blood bank in Japan and more than 39,000 pints of
blood were collected from them through the efforts of the central
bank and its mobile teams. The chief reason for refusing donors was
a history of disease, including malaria and infectious hepatitis,
and of hypertension. Only 175 positive serologies were encountered,
0.4 percent.
The low incidence of Rh-negative blood (table 35), a Japanese
racial characteristic, limited to a considerable degree any
extensive use of Japanese donors if Rh-compatible blood was to be
given to a recipient population composed chiefly of Americans and
Europeans. In the first 2,784 Japanese
732
bloods collected, there were only 19 Rh-negative bloods, 0.68
percent. The distribution according to type in 39,100 units of
Japanese blood collected in 1951 is shown in table 35. Statistics
for 1952 and 1953 were of the same order.
In 1951, almost 25 percent of the blood received in Japan by the
blood bank was procured in that country (table 36). Something over a
third of this amount was collected in Tokyo. The remainder was
collected by mobile teams at various stations in the vicinity,
including 6,456 pints from the U.S. Naval Hospital in Yokosuka and
3,308 pints from the U.S. Army Hospital in Yokohama.
TABLE 35. - Type distribution of blood
collected in Japan, 1951
| Blood type |
Bloods
|
Blood type |
| |
Number |
Percent |
Type O:
|
| Rh positive, high titer |
10,378 |
56.2 |
| Rh positive, low titer |
5,142 |
29.7 |
| Rh negative, high titer |
1,848 |
10.0 |
| Rh negative, low titer |
1,070 |
5.9 |
Total
|
18,438 |
47.1 |
Type A:
|
|
|
| Rh positive |
12,309 |
84.5 |
| Rh negative |
2,251 |
15.5 |
Total
|
14,560 |
37.2 |
Type B:
|
|
|
| Rh positive |
3,722 |
85.9 |
| Rh negative |
608 |
14.1 |
Total
|
4,330 |
11.0 |
Type AB:
|
|
|
| Rh positive |
1,511 |
85.2 |
| Rh negative |
261 |
14.8 |
Total
|
1,772 |
4.7 |
All types:
|
|
|
| Rh positive |
33,062 |
84.5 |
| Rh negative |
6,038 |
15.5 |
Grand total
|
39,100 |
--- |
TABLE 36. - Receipts of blood, Tokyo Blood Depot,
1951-52
|
Month |
1951
|
1952 |
Collected in Japan
|
Received from
Zone of Interior |
Total |
Collected in
Japan |
Received from
Zone of Interior |
Total |
| |
Number
|
Number |
Number |
Number |
Number |
Number |
| January |
2,614 |
7,060 |
9,674 |
3,274 |
9,648 |
12,922 |
| February |
4,233 |
9,264 |
13,497 |
3,509 |
8,328 |
11,837 |
| March |
2,319 |
9,224 |
11,543 |
2,218 |
8,472 |
10,690 |
| April |
2,952 |
13,466 |
16,418 |
2,163 |
8,640 |
10,803 |
| May |
3,287 |
15,032 |
18,319 |
2,177 |
8,976 |
11,153 |
| June |
3,053 |
10,528 |
13,581 |
2,725 |
7,920 |
10,645 |
| July |
2,454 |
10,392 |
12,846 |
1,986 |
7,368 |
9,354 |
| August |
1,926 |
9,048 |
10,974 |
2,356 |
7,415 |
9,771 |
| September |
2,722 |
11,496 |
14,218 |
2,555 |
7,558 |
10,113 |
| October |
5,769 |
14,424 |
20,193 |
5,882 |
9,360 |
15,242 |
| November |
3,871 |
10,632 |
14,503 |
2,337 |
8,112 |
10,449 |
| December |
3,572 |
8,639 |
12,210 |
3,321 |
8,760 |
12,081 |
Total
|
38,772 |
129,205 |
167,977 |
34,503 |
100,557 |
135,060 |
Section II. The Development of the Whole
Blood Program in the Zone of Interior
THE FIRST YEAR
Collections of blood by the American Red Cross for the Department
of Defense began in August 1950. By the middle of 1951, those
responsible for the blood and plasma program in the Department of
Defense were increasingly concerned because procurement was lagging
far behind requirements and commitments (2). Whole blood
requirements for the Armed Forces were being met, but reserves of
plasma were in alarmingly short supply because of lack of blood to
process.
On 20 July 1951, the chairman of the Armed Forces Medical Policy
Council, Dr. Lovelace, projecting present trends into the future,
reported to the Secretary of Defense that the blood procurement
program of the Department was in serious need of revision. On the
basis of a report made to the Policy Council on 16 July 1951 by an
ad hoc committee,4 Dr. Lovelace recommended that the
program be referred to the newly established Health Resources
Advisory Committee of the Office of Defense Mobilization for
information and assistance. He also recommended that the American
Red Cross Blood Donor
4 This committee consisted of
Colonel Kendrick, Chairman; Captain Newhouser, Department of
Defense; Maj. Gen. David N. W. Grant, USAF (Ret.), and Mr.
Richard Swigart, American Red Cross; and Dr. F. Douglas Lawrason
NRC.
734
Program be stimulated with the assistance and cooperation of the
Department of Defense, as follows:
1. There should be a continuously active
advertising campaign for donors.
2. Additional collection centers should be
established.
3. Blood procurement should be stimulated on the
local level in every possible way, especially when blood banks
were located in heavily populated areas and within reasonable
shipping distance of existing plasma plants.
4. The Red Cross should be requested to
establish priorities for blood for the Department of Defense.
In addition to these steps, which should be taken jointly with
the American Red Cross, Dr. Lovelace recommended that the Department
of Defense:
1. Should establish a military blood
collection program to reach military personnel and civilian
employees on military bases.
2. Should institute a policy of purchasing
plasma from civilian commercial laboratories which met NIH
specifications.
THE ARMED FORCES BLOOD DONOR PROGRAM
On 2 August 1951, in a DOD directive, the Acting Secretary of
Defense, Mr. Robert D. Lovett, announced the establishment of an
Armed Forces Blood Donor Program, "to provide a continuous and
vigorous campaign, in conjunction with the Red Cross, to persuade
the civilian and military population to contribute whole blood to
the Armed Forces" (16). The program would be launched on 10
September 1951.
The Director of Information, Office of the Secretary of Defense,
would be responsible for directing publicity and information
concerning the program. Policy guidance would be provided by the
Armed Forces Medical Policy Council, Office of the Secretary of
Defense. All programs would be coordinated through the Armed
Services Medical Procurement Agency.5
The success of the military program was immediate (figs.
169-172). Within a few months there were more donors than facilities
to handle them. The attitude of the Air Force was typical of all the
Services. On 6 September 1951, the Air Adjutant General directed
that "every level of command of the Air Force give its whole-hearted
cooperation to insure the success of the program." Effective on 10
September, the date of initiation of the program, or as soon
thereafter as possible, Air Force collection centers would be
established at Lowry Air Force Base, Denver, Colo., Lackland Air
Force Base, San Antonio, Tex., and Sheppard Air Force Base, Wichita
Falls, Tex. Tentative sites were also selected for other collection
centers, to be activated as necessary later.
5 The National Advertising Council
worked closely with the Director of Information, DOD, and
deserves much of the credit for the outstanding success of the
program.
735
FIGURE 169.-Official poster of Armed Forces Blood
Donor Program instituted September 1951.
THE NATIONAL BLOOD PROGRAM
One of the major problems of blood procurement was the necessity
of providing blood for civil defense as well as for combat needs. It
was studied by Dr. Rusk, Chairman, Health Resources Advisory
Committee, and his staff; on their recommendation, on 10 December
1951, President Truman issued an Executive order to the effect that
the Director of the Office of Defense Mobilization would provide,
within his office, "a mechanism for the authoritative coordination
of an integrated and effective program to meet the nation's
requirements for blood, blood derivatives and related substances" (17).
In this order, it was pointed out that a subcommittee on blood had
been appointed within the Health Resources Advisory Committee, to
develop "a single National Blood Program encompassing all phases of
the problem." It was the President's desire that the activities of
all departments and agencies in the field be coordinated "through
this mechanism."
736
FIGURE 170.-Shipments of blood for processing centers
secured from military installations in Zone of Interior. A. From
Fort Bragg, N.C., October 1951, by train. B. From Camp Rucker, Ala.,
October 1951, by plane. C. From Fort Leonard Wood, Mo., November
1951, by truck.
737
FIGURE 171.-Mr. William J. Richards, Red Cross
representative, Capt. Ray Jones, and Copilot Wilson Byerhoff
inspecting shipment of blood as it arrived via American Air Lines at
San Francisco Airport for transshipment to Japan, 26 August 1950.
On 18 February 1952, the Subcommittee on Blood (the Cummings
Committee) submitted a statement of basic principles upon which the
reorganized program should be based. The substance of this report,
which was immediately transmitted to the Secretary of Defense, Mr.
Lovett, was as follows (18):
1. The program created to meet the blood needs of the nation in
the time of national emergency and to be known as the National Blood
Program would represent a coordination of the blood programs already
in existence.
2. No agency would duplicate the efforts of another agency unless
the task could not otherwise be performed adequately. Before such a
duplication occurred, there must be agreement for it among the
agencies involved and the Office of Defense Mobilization.
3. The recruitment program for volunteer donors would emphasize the
National Blood Program as a whole and not any specific part thereof.
4. The Department of Defense and the Federal Civil Defense
Administration would be authorized to establish and maintain
separate plasma reserves.
5. The Red Cross would continue to be the blood collecting agency
for the National Defense Program except for the facilities (then 34)
of the Department of Defense in Armed Forces installations located
in areas not covered by the collecting facilities of the National
Red Cross. These collecting facilities now included 44 regional
programs covering 1,540 local chapters and cooperating blood banks.
738
FIGURE 172.-Representatives of Swiss and British
Armies watching as nurse takes blood from representative of Iranian
Army during visit of mobile blood unit from Louisville Regional
Blood Donor Center to Fort Knox, Ky., July 1950.On this visit, 189
donations were secured.
6. Priorities for allocation of blood would be as follows:
a. The Armed Services, for whole blood transfusions.
b. Civilian needs for whole blood and blood derivatives.
c. Allocation of the remaining blood collected for the
production of plasma and blood derivatives to meet immediate
needs and establish national reserves.
7. In the event of enemy action, the total reserves of plasma,
blood derivatives, and plasma expanders would be allocated as
necessary by Executive order.
8. The Red Cross would continue to operate, for military use only,
15 centers serving 258 local chapters and would participate in a
cooperative program with 35 civilian blood banks which would
coordinate supply.
9. Research on blood and related problems would be coordinated
through a committee set up by the National Research Council and
composed of experts in the field, including liaison representatives
from the Department of Defense. Funds would be provided for the
research projects by the participating agencies.
10. There would also be a continuing effort to train personnel in
the laboratory and clinical phases of blood supply and to foster and
provide for research, so that, in the event of another emergency,
any blood bank system setup would be operated by well-trained
medical officers thoroughly versed in all phases of military blood
banking and logistics.
These recommendations were put into effect and the national blood
program was successfully operated according to them for the
remaining years of the war.
739
Section III. The Oversea Airlift to
Korea
GENERAL
CONSIDERATIONS6
The Korean War began on 25 June 1950, and active fighting ended
on 27 July 1953, with the signing of an armistice. The formal Zone
of Interior blood supply program for Korea began on 15 August 1950,
with a radio request from the Far East Command for shipments of
blood from the Zone of Interior to augment the quantities collected
and distributed by the 406th Medical General Laboratory in Tokyo (15).
The first blood shipped in response to this message, which had been
requested for 30 August, left the temporary laboratory at the U.S.
Naval Hospital in Oakland, Calif., for Japan on 26 August 1950. On 8
February 1954, a dispatch from the Far East Command recommended that
the service be terminated, and the last blood was flown to Japan on
13 February 1954 from the Armed Services Whole Blood Processing
Laboratory, Travis Air Force Base, Calif. Between the dates of the
first and last shipments, this laboratory had received and handled
397,711 pints of whole blood, of which 340,427 pints had been
shipped to Japan for transshipment to Korea for distribution to the
various medical units of the United Nations there. The Travis
laboratory was placed on a standby basis on 13 February 1954 and was
deactivated a month later. This program was the largest operation of
its kind in the history of military medicine in the United States.
The important steps in the development of the administrative
background of the airlift of blood in the Korean War have been
described in detail elsewhere (p. 713). Many of the most important
actions, it will be remembered, were taken after fighting had
commenced.
PROCESSING LABORATORY, TRAVIS AIR FORCE BASE
Establishment
In order that the military might have a central processing
facility in which to receive blood collected by the American Red
Cross, perform necessary laboratory tests on it, package it, and
ship it to Japan for transshipment to Korea, a processing laboratory
was established at Travis Air Force Base (then Fairfield-Suisun Air
Force Base), Calif., where a Military Air Transport Service group of
the Pacific Division was located. The building selected had to be
renovated and converted for this purpose, and until it was ready, on
25 September 1950, a temporary laboratory was set up and operated in
the U.S. Naval Hospital at Oakland, Calif., about 50 miles away.
6 Unless otherwise specified, the
material concerning the airlift is derived from the history of
the Armed Services Whole Blood Processing Laboratory, Travis Air
Force Base, Calif., 25 August 1950-15 March 1954 (19).
740
During the war, a number of attempts were made to establish a
blood processing laboratory on the east coast, but no definitive
action was ever taken, though supplies and personnel were earmarked
for an emergency standby facility at the U.S. Naval Hospital,
Chelsea, Mass. This facility was not called upon, but it was
expected that, if it had been, it could have begun to ship blood to
Japan within 24 hours after activation.
Functions
The Armed Services Whole Blood Processing Laboratory at Travis
Air Force Base performed the following functions:
1. It received whole blood from the American Red Cross, performed
appropriate laboratory tests on it, and shipped it to the Far East
Command for use in Korea.
2. It maintained a record of all bloods received in the laboratory
and their disposition.
3. It coordinated whole blood requirements with the Armed Services
Blood and Blood Derivatives Group and the appropriate
representatives of the American Red Cross.
4. It maintained a close working arrangement with the medical supply
section of the Travis Air Force Base in requisitioning and drawing
of supplies required in the day-to-day operations of the laboratory.
5. It maintained liaison with other military organizations and
civilian agencies as necessary for efficient accomplishment of its
mission.
6. It prepared and submitted to the chairman of the Armed Services
Blood and Blood Derivatives Group routine reports and such special
reports as were requested.
Facilities and Equipment
Structures of the permanent laboratory included a building of
3,400 sq. ft. and two warehouses, respectively 2,786 and 800 square
feet. All buildings, office equipment and supplies, housekeeping
items, heat, electricity, gas, communication services, and motor
vehicle transportation were furnished to the laboratory and
maintained by the Travis Air Force Base. Billeting and messing
facilities for laboratory personnel were also furnished by Travis
Air Force Base. A Navy panel truck, on loan from Oakland Naval
Hospital, was assigned to the laboratory for general use.
The building at Travis Air Force Base that was converted into a
laboratory was an old hospital messhall. The conversion required the
installation of lighting fixtures, water-distilling apparatus,
refrigerators, sinks, laboratory counters and workbenches, and
natural gas fixtures. The precooling room and warehouses were not
completed until about 8 months after the laboratory was occupied.
When the converted building was taken over, however, on 25 September
1950, everything else was in such good order that a shipment of
blood could be sent to Japan the same day.
Initial medical supplies and equipment were procured directly
from the Oakland Naval Medical Supply Depot. Later, by agreement
among the three Services, the requirements and stock control section
of the Supply
741
Division, Office of The Surgeon General, U.S. Army, was given the
responsibility of furnishing medical supplies and equipment to the
laboratory. All requisitions went through the Travis Air Force Base
medical supply section to the Alameda Army Medical Supply Depot.
The operational cost of this laboratory was estimated at over $1
million a year. It cost approximately $17.83 to procure and process
a pint of blood and transport it from the United States to the Far
East Command in Japan, this sum including $6.56 paid to the Red
Cross for processing services, $9.40 for laboratory expenses, and
$1.87 for transportation costs.
Personnel
Four Navy blood bank technicians arrived from the east coast at
the laboratory on 23 August 1950. Office, laboratory, and cold
storage spaces were made available to them at once, and supplies and
equipment were procured from the hospital and from the U.S. Naval
Medical Supply Depot in Oakland. As a result, 48 hours after these
technicians had arrived, the first whole blood shipment (1,488
pints) was received, processed, and delivered to the Military Air
Transport Service at Travis Air Force Base for transshipment to
Japan.
Requests for additional laboratory personnel were at first
handled very slowly, and, by the middle of September 1950, the staff
working in the Oakland laboratory included, in addition to the four
original technicians, only one Navy Medical Service Corps officer
and three laboratory technicians. Laboratory technicians were
borrowed from Oakland and Mare Island Naval Hospitals and from
Letterman General Hospital, San Francisco, Calif. Clerical and some
general duty helpers were borrowed from Travis Air Force Base and
the Oakland Naval Hospital. Additional duty corpsmen and
convalescent patients aided on a day-to-day basis. All of these men
were returned to their duty stations when additional permanent
personnel began to arrive about the middle of October. In spite of
its personnel difficulties, the laboratory handled over 7,000 pints
of whole blood during the weeks of its operation at the U.S. Naval
Hospital in Oakland.
In the approximately 42 months of its operation, an average of 35
persons were regularly attached to the laboratory, including an
average of 11 from the Army, 10 from the Navy, and 14 from the Air
Force (fig. 173).
Training.-A quick, efficient blood bank technique can be
acquired only by experience, and most of the personnel assigned to
the Travis laboratory were inexperienced. All therefore worked long
hours while they were receiving individual instruction. A formal
training program was set up a few months after the laboratory was
activated, and 59 persons completed the course of instruction,
including 14 Air Force Medical Service Corps officers, 34 Army
enlisted men, and 11 Air Force enlisted men.
742
FIGURE 173.-Personnel of Travis Air Force Base Whole
Blood Processing Center. Seated, left to right, M. Sgt. John F.
Firmani, USA, NCOIC (Noncommissioned Officer in Charge) of Blood
Processing Department and head of Section III; M. Sgt. Marvin C.
Lynn, USAF, leader, Laboratory Section III; Lt. James H. Parker,
MSC, USN, officer in charge; 1st Lt. William R. Bonnington, MSC,
USAF, assistant officer in charge; M. Sgt. Joseph F. Firmani, USA,
NCOIC of Supply Section; M. Sgt. Milton L. Burgeson, USAF,
administrative assistant to OIC and NCOIC, Records Section.
Standing, Sgt. Henry M. Sottnek, USA, leader,
Receiving-Storage-Shipping Section II; T. Sgt. Alvis E. Hotchkiss,
USAF, leader, laboratory Section II; M. Sgt. Leon C. Branum, USA,
NCOIC of Blood Processing Department and head of Section II; HM1
Sherwood J. Syverson, USN, blood bank technician; and S. Sgt. John
E. Ahearn, USAF, leader, Receiving-Storage-Shipping Section III.
Work Schedules
Because of its short life, 21 days at best, expeditious as well
as expert handling of blood is necessary, and the work schedule at
the Travis laboratory was geared to that consideration. Blood from
the collection centers was shipped by air, rail, or motor transport,
as most convenient. Centers near the laboratory delivered their
blood by motor transport. Blood from distant collection centers
arrived by air. The shipments were offloaded at airports in San
Francisco or Oakland, where they were picked up by the Railway
Express Agency and transshipped by train to Fairfield-Suisun, about
7 miles from Travis. Here, they were offloaded and trucked to the
laboratory by the agency. Blood from centers nearer the laboratory
was sent by train and delivered to the laboratory by the Railway
Express Agency. Because the agency worked on a 5-day workweek
schedule, arrangements were made with the motor pool at Travis Air
Force Base to meet trains on Saturdays, Sundays, and holidays, pick
up the blood and deliver it to the laboratory.
The Red Cross blood donor centers also worked on a 5-day week,
usually Monday through Friday. Few collections were made on
Saturdays, Sundays, and holidays.
Each Friday, and oftener if requirements changed, the officer in
charge of the laboratory at Travis Air Force Base notified the
central office of the Red Cross of the quotas of blood desired for
the following week. The Red Cross, in turn, designated the donor
centers which would collect, process, and ship these quotas. A
number of attempts were made, all unsuccessful, to have the weekly
quotas collected in equal amounts on each of the 5 days weekly that
the centers operated. Few bloods were received from Monday through
Wednesday, often not the equivalent of the amounts shipped to Japan.
Most bloods were processed from Thursday through Sunday. By Sunday
night, the refrigerators were filled, and there was sufficient blood
on hand for the Monday-through-Wednesday shipments.
Although bloods arrived in the laboratory at all hours of the day
and night, most of them arrived twice daily, at 1000 and 1800 hours.
On Sundays and holidays, the bulk of the blood usually arrived at
1800 hours.
Because of these various circumstances, the Travis laboratory had
to operate 7 days a week, day and night. After additional personnel
arrived at the laboratory in October 1950, separate day- and
night-working sections were established to receive, process, and
ship blood. The two sections, each composed of equal numbers of
clerical, laboratory, and general duty personnel, alternated day-
and night-working hours at weekly intervals. A third section,
composed of administrative and supply personnel, carried on the
administrative and supply duties of the laboratory. This section
worked a regular day shift, but its personnel were subject to night
call as necessary.
LABORATORY ROUTINE
Collection and Initial Processing
Only proved group-O blood, of low titer and Rh-verified, was sent
to Korea. As in World War II, about 45 percent of random donors
proved to be group O, and about a quarter of this group had
agglutinin titers above 1:64.
The technique of collection was essentially that employed in
World War II (p. 145). Donors were screened to make sure that they
were group O. Whole blood intended for oversea use was collected in
ACD solution (blood intended for plasma was collected in sodium
citrate solution). The blood was collected in 500-cc. amounts in
sterile, pyrogen-free bottles; samples for serologic testing and
crossmatching were collected into pilot tubes. The collection
bottles were not entered again until the recipient sets were
attached just before the transfusions were to be given. With this
precaution, there was no possibility of contamination and there is
no record that any occurred.
744
After the blood had been collected, two technicians performed two
separate tests for specificity. With this doublecheck, the
percentage of error did not exceed 0.5 percent, and there was not a
single report of incompatibility during the course of the war. This
was a remarkable record, for the blood that arrived at the
processing center at Travis Air Force Base came from donor centers
all over the United States.
Serologic tests were also performed, even though by this time
there was valid evidence that syphilis could not be transmitted by
blood that had been stored longer than 3 days (p. 143).7
Later Processing
After the collected blood had been chilled to 39.2º to 42.8º F.
(4º to 6° C.), it was shipped by truck, rail, or air to the
processing center in insulated Church shipping cases, refrigerated
with wet ice (p. 204). Blood usually arrived within 48 hours after
it had been collected. At the base, it was taken to the receiving,
storage, and shipping section; logged in; placed in a walk-in
refrigerator maintained in the temperature range just mentioned; and
there unpacked, inventoried, and stored. Two such refrigerators were
available, each capable of holding 2,500 pints of blood. The empty
insulated blood shipping container was readdressed to the blood
donor center whence it had come, and was returned to the center by
Railway Express.
The pilot tube containing 6-8 cc. of whole blood was detached
from the bottle and taken to the laboratory section, where the
sample was regrouped, retyped, and retitered (fig. 174). The
repetition of these tests served two purposes: (1) It eliminated
units of blood that were not group 0. (2) It served, to a degree, as
a crossmatch; it was not always possible for medical units in Korea
to type and crossmatch their patients before transfusing them.
Each year the Travis laboratory used approximately 9,600 cc. of
anti-A and anti-B, and 5,800 cc. of anti-Rh, blood typing sera.
During the last month the laboratory operated, the sera were used in
dried form. The liquid form, which had been used up to this time,
was thought more satisfactory, for several reasons: It contained
fewer artifacts. It saved time because it did not have to be
reconstituted. It was packaged in smaller units, and less warehouse
space was required to maintain an adequate supply. On the other
hand, the dried form cost a little less and had a longer useful
life, 60 months, against 12 months for the liquid form. There was no
significant difference in the number of bloods that could be tested
with given amounts of each form.
After testing, a label was securely glued to each bottle,
containing the unit blood number, blood group, Rh-factor, point of
origin, and original blood donor center number. Although the
expiration date did not ordinarily exceed
7 At the meeting of the Committee
on Blood and Blood Derivatives on 23 September 1953 (after the
armistice bad been signed), it was proposed by Dr. William G.
Workman that serologically positive bloods be used for the
preparation of dried plasma, and that bloods intended for these
purposes should not be tested serologically (20). These
proposals were concurred in by Dr. Thomas B. Turner, Dean, Johns
Hopkins University School of Public Health, and were recommended
for action by the committee.
745
FIGURE 174.-Laboratories at blood processing center,
Travis Air Force Base. A and B. Typing, titration, and Rh-testing
laboratory. C. Typing laboratory. Note slides with wells, a
post-World-War-II development.
21 days, an expiration date of 22 days from the date of
collection was placed on each bottle because this blood would be
shipped across the international date line for use in a later time
zone. If the serum agglutinin titer of a unit exceeded 1:256, the
label read, High Titer Group "O" Blood-For Group "O" Recipient
Only. If the titer was less than 1:256, the label simply read
Low Titer.
746
FIGURE 175.-Containers of whole blood loaded on
Military Air Transport Service trailers for delivery to plane that
will fly it to Korea, Travis Air Force Base blood processing center,
1952.
Shipment
During the Korean War, the processing laboratory at Travis Air
Force Base maintained in store two or three times the estimated
daily requirement of blood, so that emergency requests could be met
without delay. When such a request was received, the blood was given
a No. 1 priority and sent to Japan immediately on a cargo or
passenger plane.
If circumstances permitted, the blood was held in the
refrigerator for 8 to 12 hours, so that it could be examined grossly
for hemolysis, clots, or excessive fat content. Frequently, however,
because of the heavy demands, bloods were processed and shipped out
on the same day that they were received. They were packed for
shipment in the walk-in refrigerators.
Except in emergencies as just noted, all whole blood shipped from
the United States to the Far East Command was transported in
aircraft of the Military Air Transport Service (figs. 175 and 176).
It was flown from Travis Air Force Base to Haneda Air Force Base
near Tokyo, with stops at Honolulu and Wake Island (map 7). It was
reiced at these stops if necessary. As soon as the blood arrived in
Japan (fig. 177), it was removed from the plane, trucked to the
blood storage section of the 406th Medical General Laboratory, and
stored there until it was shipped to Tokyo and thence to Korea (fig.
178). All blood moved in Korea was transported by plane or
helicopter (fig. 179).
747
FIGURE 176.-Boxes of blood being loaded on plane for
flight from Travis Air Force Base to Tokyo Blood Bank.
STATISTICAL DATA
The largest number of bloods received, tested, and labeled in the
Travis laboratory in a single day was 1,881 pints. The overall daily
average was 319 pints, based on a 7-day week for the almost 42
months during which the laboratory operated.
The largest number of bloods handled in a single day by the
receiving and shipping section was 2,500 pints, this number
including both units received and units shipped. The largest
shipment placed in a single plane for shipment to Japan was 1,488
pints. The average daily shipment was 273 pints.
The total weight of the blood and recipient sets shipped to Japan
was 1,782,434 pounds (891 tons) and the total space required for the
shipments, 426,379 cubic feet.
Of the 397,711 pints of whole blood received in the processing
laboratory, 340,427 (about 85 percent), were shipped to the Far East
Command for use in Korea. The remaining 15 percent included surplus
bloods and bloods which for other reasons (hemolysis, clots,
breakage, excessive fat content, volume less than 500 cc.) could not
be used for transfusions. Most of it (56,809 pints) was sent to the
Cutter Laboratories, Berkeley, Calif., for plasma fractionation, but
347 pints were used in local military hospitals. Breakage involved
only 128 bottles; 94 were received broken, and 34 were broken during
processing.
748
MAP 7.-Flight plan, for airlift of blood from Travis
Air Force Base, Oakland, Calif., to Tokyo Blood Bank, and thence to
Korea.
Only 144 of the bloods received in the laboratory were not group
O; 116 were group A, 24 group B, and 4 group AB. These units had
been either mistyped or mislabeled at the original blood donor
centers, and the errors were caught when they were retyped in the
laboratory. The remarkably low percentage of misgrouped blood
indicates the skill and care of the technicians who did the initial
grouping and labeling. Theirs was a most responsible task, for, as
already mentioned, most group-O blood used in Korea, as in World War
II, was not crossmatched before it was used.
About 10 percent of all the blood received had an agglutinin
titer of 1:256 or higher. During the first 18 months the laboratory
operated, less than 9 percent of the bloods received were
Rh-negative. During the last 2 years, because of repeated requests
for such bloods, the proportion rose to 12 percent. Rh-negative
blood was not sent to Korea but was used in the fixed installations
in Japan, since it was in them that Rh-negative casualties might
receive repeated transfusions 10 to 14 days after they had received
Rh-positive blood in forward hospitals.
749
FIGURE 177.-Blood flown from blood processing center,
Travis Air Force Base, to Japan. A. One of first shipments of blood
from United States, stored in medical depot in Yokohama, August,
1950. B. Boxes of blood just received at Haneda Air Force Base,
Tokyo, November 1950.
750
FIGURE 178.-Blood, flown from United States via
Tokyo, on arrival in Korea. Blood being unloaded by native labor at
Seoul Air Field, Korea, whence it will be transshipped to 11th
Evacuation Hospital, February 1952.
Losses.- As has just been indicated, most of the blood
rejected for oversea shipment for various reasons was made into
albumin and immune serum globulin, so that the overall loss was very
slight.
Losses remained at about the same level during most of the war.
The heaviest losses occurred in the winter of 1950-51, when, because
of inadequate processing facilities in the East, bloods intended for
plasma, which had to be shipped to a laboratory on the west coast,
froze en route. Otherwise, losses remained at about the same level
during most of the war. In March 1952, losses amounted to 4.4
percent (2 percent hemolysis, 2 percent short amounts, 0.004 percent
lipemia, and 0.4 percent other causes).
751
FIGURE 179.-Transportation of blood by helicopter, in
Korea. A. Blood being loaded for emergency shipment to frontlines.
Note that ports of this model of helicopter admit only marmite cans.
On return trip, a casualty will be brought back. B. Blood for
emergency use in forward mobile army surgical hospital being placed
aboard helicopter, Chunchon, Korea, December 1951. C. Helicopter,
loaded with whole blood, ready for takeoff, June 1953.
752
Section IV. The Whole Blood Oversea
Experience
ESTIMATE
OF NEEDS
Experience in the European theater in World War II showed that an
army in action, meeting stiff resistance would require about 500
pints of blood a day, the requirement varying with the type of
fighting (p. 557). As would be expected, it was found that the
faster an army moved, as in a breakthrough, the less blood would be
required. During conventional fighting, in order to keep units
supplied with their daily requirements, theater inventories of blood
had to be maintained at two to three times normal daily
requirements.
These rules of thumb proved quite acceptable for conventional
military requirements in Korea (table 37). Estimates for total blood
needs were predicated on estimated casualty rates. Requirements
usually worked out at 1½ to 2 pints for each hospitalized casualty.
Since delivery of blood from the Zone of Interior could not
immediately reflect increased demands from Korea, the policy was to
maintain a rather constant demand upon Zone of Interior sources and
adjust collections of blood as necessary in Japan.
DISTRIBUTION
At the beginning of the oversea blood program, all blood received
in Japan from the Zone of Interior was sent to Korea, while blood
collected at the 406th Medical General Laboratory blood bank was
used only at fixed hospitals in Japan. Within a short time this
policy was changed and all blood was handled at the bank on an
integrated basis.
When requisitions from Korea were received, the blood was flown
to a distribution point in Korea (chart 14), where a distribution
team received it from the courier who had accompanied it. Early in
the war, when the fighting was highly fluid, two blood depots were
maintained, both in the southern part of the peninsula. Later, as
the front stabilized, several subdepots were established farther
north. By the end of 1951, three depots were in close support of the
front, and two supplied rear areas. Helicopters proved the most
efficient way of distributing blood to forward units (fig. 179) as
they could evacuate casualties on the return trip.
During 1952, reserve blood depots were maintained in Korea at
Pusan and Seoul, and three advanced depots were maintained in Eighth
U.S. Army areas. In addition, many hospitals stored reserves of
blood to meet possible emergencies.
In Korea, although whole blood was considered a special item, it
was handled in medical supply channels. The Supply Service deserves
great credit for its cooperation and competence, but personnel
intimately connected with the blood program could not accept this
concept of handling whole blood. The operation of a blood bank
system, including distribution,
753
TABLE 37. - Ratio of blood issued to
wounded in action, 1951-52
|
Month |
1951 |
1952
|
| WIA1 |
Blood sent to Korea2 |
Ratio WIA/blood |
WIA
|
Blood sent to Eighth U.S. Army |
Ratio WIA/blood |
U.S. forces
|
U.N. forces |
ROK forces |
Total |
U.S. forces |
U.S.-U.N.
forces |
Total3
forces |
| January |
2,789 |
4,989 |
1.79 |
727 |
88 |
1,208 |
2,023 |
7,432 |
10.22 |
9.12 |
3.67 |
| February |
4,731 |
9,178 |
1.94 |
550 |
99 |
570 |
1,219 |
7,008 |
12.74 |
10.80 |
5.75 |
| March |
4,834 |
9,629 |
1.99 |
477 |
117 |
367 |
961 |
7,440 |
15.60 |
12.53 |
7.74 |
| April |
4,853 |
12,108 |
2.49 |
726 |
107 |
742 |
1,575 |
7,200 |
9.92 |
8.64 |
4.57 |
| May |
4,507 |
13,366 |
2.97 |
882 |
170 |
795 |
1,847 |
7,056 |
8.00 |
6.71 |
3.82 |
| June |
3,436 |
10,366 |
3.02 |
1,869 |
212 |
1,948 |
4,029 |
7,448 |
3.98 |
3.58 |
1.85 |
| July |
1,628 |
9,624 |
5.91 |
1,594 |
251 |
1,694 |
3,539 |
6,321 |
3.97 |
3.43 |
1.79 |
| August |
1,707 |
8,112 |
4.75 |
1,594 |
241 |
1,043 |
2,878 |
6,209 |
3.90 |
3.38 |
2.16 |
| September |
6,539 |
9,864 |
1.51 |
1,874 |
256 |
2,563 |
4,693 |
6,801 |
3.63 |
3.19 |
1.45 |
| October |
9,968 |
14,056 |
1.41 |
3,767 |
303 |
9,583 |
13,643 |
9,571 |
2.55 |
2.36 |
0.70 |
| November |
2,647 |
12,482 |
4.72 |
1,262 |
383 |
4,079 |
5,724 |
6,720 |
5.32 |
4.09 |
1.17 |
| December |
1,147 |
10,036 |
8.75 |
607 |
114 |
1,511 |
2,232 |
7,497 |
12.35 |
10.40 |
3.36 |
Total |
48,786 |
123,810 |
2.54 |
15,929 |
2,341 |
26,103 |
44,363 |
86,703 |
5.45 |
4.75 |
1.95 |
1U.S. and U.N. forces,
without ROK forces.
2In 500-cc. units.
3U.S., U.N., ROK forces.
754
CHART 14.-Organization for distribution of whole
blood for Korea
these personnel argued, is not a supply problem but a
professional logistic project requiring the highest degree of
coordination on the part of skilled professional personnel. In their
opinion, later concurred in by the investigating officer who made a
special survey of the blood program in Korea (p. 755), there should
be in every theater a transfusion officer with the responsibility of
supplying blood to the armies. By supply standards, the multiple
supply points just listed were entirely reasonable. By standards of
trained transfusion officers, this policy was inefficient and
wasteful because it permitted blood to age in storage.
Aging
It was almost impossible to collect precise data concerning the
age of blood received and used in Eighth U.S. Army installations in
Korea after it had left the base depot. In 1951, it was estimated
that when blood reached the Haneda Air Force Base in Japan from the
Zone of Interior, it was 6 days old, which meant that it had an
average usable remaining life of 15 days
755
(table 38). When the blood was received in Korea, the average
remaining life was 9.4 usable days. Fragmentary reports from forward
hospitals indicated that when it was used, it was from 9 to 20 days
old.
TABLE 38. - Remaining usable days of blood
received from Zone of Interior and shipped to Korea, 1951
|
Month |
Receipts from Zone of Interior
|
Average number
usable days |
Shipments to
Korea |
Average number
usable days |
|
January |
7,064 |
9.5 |
4,989 |
7.1 |
|
February |
9,264 |
13.6 |
9,178 |
12.4 |
|
March |
9,224 |
13.9 |
9,629 |
10.2 |
|
April |
13,466 |
--- |
12,108 |
10.0 |
|
May |
15,032 |
12.3 |
13,366 |
10.3 |
|
June |
10,528 |
13.5 |
10,368 |
9.3 |
|
July |
10,392 |
13.5 |
9,624 |
7.1 |
|
August |
10,974 |
12.0 |
8,112 |
8.2 |
|
September |
11,496 |
13.5 |
9,960 |
9.5 |
|
October |
14,424 |
12.6 |
14,046 |
9.2 |
|
November |
10,632 |
13.8 |
11,676 |
9.9 |
|
December |
8,639 |
10.1 |
9,138 |
9.3 |
Medical officers and trained blood bank workers realize the
importance of issuing blood that is as fresh as possible, knowing
that the older the blood, the faster will red cells break down after
transfusion, the less effective is the transfusion, and the more
blood must eventually be used. Since supply personnel did not
realize this, their policy in Korea in respect to blood was, as with
other supplies, to issue the oldest blood first, to get rid of it.
A number of studies by the fragility test were made daily for 10
days on blood that was 8 to 10 days outdated, in the hope that some
safe extension of the expiration date could be determined. Although
cell fragility was not notably increased over the testing period, no
evidence was adduced to encourage the idea that overage blood should
be used deliberately.
SURVEY OF WHOLE BLOOD EXPERIENCE, FAR EAST
COMMAND
On 11 March 1953, Lt. Col. Arthur Steer, MC, submitted a report
to the Chief Surgeon, U.S. Army Forces, Far East, on a 14-day survey
made in October 1952 and dealing with the use and supply of whole
blood in this command (21). During October, both U.S. and ROK
(Republic of Korea) troops sustained higher casualties than at any
other time in 1952. The survey was confined to the Eighth U.S. Army
area.
Use factor.-Colonel Steer noted that the data he had
collected were somewhat difficult to interpret because no policy had
been established for the
756
issuance of blood to ROK units. ROK units were not supposed to be
evacuated through Eighth U.S. Army installations, but a significant,
though unknown, number, particularly in troops attached to U.S.
units, had thus been evacuated and so had been transfused by U.S.
Army standards.
During the period of the survey, approximately 20 percent of all
U.S. and U.N. (United Nations) casualties, other than ROK wounded,
were transfused, at an average rate of 4.4 bottles per casualty or
0.9 bottles per U.S. wounded who reached a medical treatment
facility. On the basis of U.S. casualties only, 5.54 bottles were
issued per each soldier wounded in action. If all casualties,
including ROK casualties, are considered, 1.95 bottles were issued
per each soldier wounded in action. The true issue factor thus lay
somewhere between 1.95 and 5.54 bottles per U.S. and other U.N.
casualties except ROK casualties.
Reserves.-All medical installations and depots surveyed
were found to maintain reserves of blood which provided, in toto, an
average stock on hand of 7.87 times the average daily amount used
and 3.1 times the maximum ever used on any single day. In a sense,
this blood was not wasted because aging blood was sent to ROK
installations, which were given it at an average age of 16.1 days.
The figures, however, "illustrate the compounding effect of reserve
levels resulting from the maintenance of multiple depots."
Furthermore, the existence of these multiple depots and the
maintenance of reserve stocks inevitably resulted in the aging of
blood on the shelves. This policy also made the control of reserve
levels, as well as flexibility in the use of reserves, extremely
difficult. When activity was increased in one portion of the line,
for instance, increased needs should have been met by transferring
blood to it from a hospital or depot supporting an inactive portion
of the front. Instead, they were met by requisitioning more blood
from rear areas, where it was supplied without question because
there was no single medical officer in charge of the blood supply
and with authority to question the requisitions.
Reactions.-During the survey period, there were only 19
reactions (2.5 percent) in the 757 identified patients who received
blood. Most of the reactions were mild and of the urticarial type.
One hospital, which gave transfusions to 57 patients, reported 11 of
the 19 reactions.
Recommendations
Colonel Steer's most important recommendation was that a
continuing study be made of the use of whole blood and blood
substitutes in Korea, with particular reference to the establishment
of a separate medical unit, commanded by a medical officer, whose
sole responsibility would be the procurement, storage, and
distribution of blood and blood substitutes. For two reasons, such a
study should be made by a team sent from the Zone of Interior to the
Far East Command by the Department of the Army: (1) Numerically,
there were no personnel in the theater who could be detached for the
purpose and (2) more important, there were no experienced blood bank
operators in the
757
command. Colonel Steer also considered it important that the
group which made the study should have had no previous experience
with the control of blood in supply channels and thus would be
entirely free from bias.
Another recommendation in Colonel Steer's March 1953 report was
that general hospitals outside the Tokyo-Yokohama area in Japan
establish small blood banks, subject to frequent supervisory
inspections. In the event of emergency, these banks would be
provided with blood from the Tokyo bank.
In a later communication to Colonel Kendrick on 15 December 1953,
Colonel Steer again emphasized the need for a medical officer in a
theater of combat, under the theater surgeon, able to travel in all
zones, and to be totally responsible for this blood program (22).
This would involve the setting up of minimum standards for local
blood collection practices and for shipping and storage procedures,
control of the flow and distribution of blood, establishment of
minimum bank levels, advice to the surgeon on policies and publicity
concerning blood, and constant inspection of all agencies involved
in the handling or using of blood. When this recommendation was
made, the armistice had been signed, and, within another 2 months,
the oversea airlift would be discontinued.
STATISTICAL DATA
The distribution of blood by the Tokyo Blood Depot to hospitals
in Japan and in Korea for 1951-52 is contained in table 39.
TABLE 39. - Distribution of blood by Tokyo
Blood Depot, 1951-52
|
Month |
Distribution, 1951—
|
Distribution, 1952— |
|
To hospitals in Japan
|
To depots in
Korea |
Total |
To hospitals
in Japan |
To
Communications Zone, Korea |
To Eighth U.S.
Army, Korea |
Total |
|
January |
2,295 |
4,989 |
7,284 |
2,026 |
3,504 |
7,432 |
12,962 |
|
February |
2,546 |
9,178 |
11,724 |
1,776 |
2,221 |
7,008 |
11,005 |
|
March |
2,588 |
9,629 |
12,217 |
1,380 |
3,010 |
7,440 |
11,830 |
|
April |
2,132 |
12,108 |
14,240 |
1,611 |
2,319 |
7,200 |
11,130 |
|
May |
2,540 |
13,366 |
15,906 |
1,029 |
3,424 |
7,056 |
11,509 |
|
June |
2,466 |
10,368 |
12,834 |
1,473 |
2,292 |
7,448 |
11,213 |
|
July |
2,037 |
9,624 |
11,661 |
1,420 |
1,615 |
6,321 |
9,356 |
|
August |
1,664 |
8,112 |
9,776 |
1,478 |
1,312 |
6,209 |
8,999 |
|
September |
2,574 |
9,864 |
12,438 |
1,591 |
1,392 |
6,801 |
9,784 |
|
October |
6,150 |
14,056 |
20,206 |
2,484 |
2,568 |
9,571 |
14,623 |
|
November |
2,517 |
12,482 |
14,999 |
1,951 |
2,724 |
6,720 |
11,395 |
|
December |
2,299 |
10,036 |
12,335 |
1,488 |
2,712 |
7,497 |
11,697 |
Total
|
31,808 |
123,812 |
155,620 |
19,707 |
29,093 |
86,703 |
135,503 |
758
Section V. Equipment and Refrigeration
for Airlift
PLASTIC
CONTAINERS
Development of Criteria
Plastic equipment came under discussion at the Symposium on Blood
Preservation held under the auspices of the Committee on Blood and
Blood Derivatives, NRC, on 2 December 1949 (28). Dr. Carl W. Walter,
who had been working on its development for some time for the
American Red Cross, laid down the criteria for it as follows:
1. Simple, one-piece equipment that would permit hermetic
sealing during processing, storage, and transportation of the
blood and that could be employed with a bacteriological safe
technique.
2. A slow rate of collection, causing minimal physiologic
disturbance to the donor.
3. The elimination of air vents, both during collection (by
venous pressure and gravity) and during administration.
4. Transparency.
5. Nonwettability.
6. Compressibility, to permit positive pressure infusion.
7. Stability to sterilizing temperatures (121' C. for 30
minutes).
8. Low vapor transmission.
9. Good tissue tolerance.
It was additionally specified, in view of the logistic
difficulties which the use of blood presents in times of war and
disaster, that plastic equipment recommended must be lightweight,
nonbreakable, collapsible, and sized to accommodate the volume of
liquid it was intended to contain. Also, it must be inexpensive
enough to warrant discarding after a single using but, at the same
time, it must be so designed that, in emergencies, it could be
cleaned and reused without risk of pyrogenic reactions.
First Model
Dr. Walter's studies had been carried out with equipment
fabricated from elastic thermoplastic vinylite resin that
incorporated an ion-exchange column (p. 770) of sulfonated
polystyrene copolymer. It was sealed by dielectrically induced heat
and was sufficiently elastic to yield a hermetic seal if a single
throw knot in it were stretched tightly and then released. It was
tough and flexible and provoked minimal tissue reaction. The tubing
for both donor and recipient sets was extruded with a lumen 3 min.
in diameter and a wall 0.5 mm. thick.
The bag was available in any desired capacity and could be so
compartmentalized that a single donation of blood could be
subdivided into multiple isolated amounts, each with its own
delivery tube for use in multiple small transfusions.
759
The bag, together with tile filled exchange column, fitted with a
needle and cannula, was sterilized at 250° F. (121° C.) for 30
minutes. Compressed air was then admitted to the sterilizing chamber
to maintain a pressure of 1.4 kg. per square centimeter until the
bag had cooled to 194° F. (90° C.). The assembly was ready for use
as soon as the pressure had vented.
The cost of the equipment described by Dr. Walter was then $1.48
per unit, but, when the bags were in mass production, it was
expected that the unit cost would be reduced to 45 to 50 cents.
Operation.-Blood was collected in this apparatus
essentially as in regular collecting bottles. After the bag had been
filled by gravity, the tourniquet was released and a spring clip was
placed across the tube distal to the exchange column. Samples for
testing were collected in pilot tubes before the needle was removed
from the vein. The tube was sealed or knotted close to the bag, and
the bag of blood, after being hermetically sealed, was refrigerated.
The transfusion could be given by suspending the bag from a
gravity pole by the grommet provided, or the blood could be squeezed
into the recipient's vein by placing the bag under his shoulder or
buttock. If rapid transfusion was desired, the intra-arterial
technique was used, or the operator could stand on the bag.
Comment.-The bag described by Dr. Walter had obvious
advantages. Although it took slightly longer to collect the blood
than when collecting bottles were used, the quality and yield of
blood collected was equal, if not superior, to the quality and yield
of blood collected in bottles. Moreover, blood collected in plastic
bags practically never had to be discarded because of hemolysis. The
bags did not require refrigeration before the blood was collected. A
plastic bag containing 500 cc. of blood occupied in the refrigerator
only half the space of a bottle holding the same amount. Finally,
the insulated containers developed toward the end of the war for the
transportation of blood held 48 bags instead of 24 bottles.
Testing and Adoption
By March 1950, the Walter apparatus was in commercial production,
by the Fenwal Co., and comparable equipment had been developed by
the Abbott Laboratories.
When the ad hoc committee on plastic bag collecting equipment
reported on 8 October 1951, plastic equipment had received
sufficiently extensive testing in various military and civilian
hospitals to establish its desirability and efficiency (24).
Further testing was planned for civilian hospitals and Red Cross
blood donor centers, and field trials were planned for the Army
under what was termed extreme conditions. Figures 180 and 181
illustrate the final type of plastic equipment developed in the
Korean War and demonstrate its use. These bags were never formally
used in the blood program in Korea because of objections raised to
them by
760
FIGURE 180.-Plastic equipment, standardized as
replacement for glass bottles during Korean War. In center is
collecting bottle formerly used.
the American Red Cross. They came into general use in military
hospitals, though only after some indoctrination. Medical officers
at first did not like the plastic equipment, particularly the resin
column, and there was some resistance to the use of the bags, even
when the blood was collected in ACD solution. At Walter Reed General
Hospital, Washington, D.C., where a large-scale test was conducted,
it was found worthwhile to have an experienced nurse indoctrinate
all personnel in their use.
REFRIGERATED SHIPPING CONTAINERS
Up to the spring of 1951, blood was shipped from the Whole Blood
Processing Laboratory at Travis Air Force Base in the Navy (fig.
139, p. 611) and the Army (fig. 182, p. 762) insulated containers
developed for use in World War II. The Army boxes did not hold up
too well (fig. 183), and when the supply was exhausted, other models
were tested (19).
Bailey container.-The first shipping container procured
from the Bailey Co. was designed on the principle of the Army box.
It had an outside measurement of 8 cu. ft., held 24 pints of blood,
and weighed 115 pounds when fully packed and iced.
The outer shell of the Bailey box was made of fiberboard or
V-board, which was supposed to be water-resistant. The insulating
mechanism moisture-vapor barrier, lid, and ice cans were similar to
those used in the Army container.
761
FIGURE 181.-Demonstration of use of plastic
equipment. A. Collection of blood, Fort Sam Houston, April 1952. B.
Demonstration of transfusion by gravity by personnel of Walter Reed
General Hospital in field tests, June 1952. C. Accelerating rate of
blood flow during transfusion by placing bag, which is
break-resistant, beneath patient's body.
Sufficient space was allotted for recipient sets, but, in the
first model, the wire racks were so close together that the larger
type of blood bottle did not fit between the separators.
When the box was closed, it was secured by wingnuts on each side,
and handles of sashcord were attached on the same sides. This
arrangement made it impossible for personnel to lift the container
by the cord handles without scraping their hands on the nuts. As
long as the first Bailey container was used, shipping and receiving
personnel at the Travis laboratory could be identified by their
bruised hands.
762
FIGURE 182.-Army insulated box, developed late in
World War II and used in early airlift to Korea. Boxes are being
moved into air-conditioned receiving and shipping room, Travis Air
Force Base processing laboratory.
In spite of its defects, this container maintained the proper
temperature for blood during its transportation to Japan, and about
2,000 were used. In the meantime, a new model was devised, with a
number of improvements, including the attachment of the cord handles
and the nuts on different sides. This model, 1,200 of which were
delivered, had, like the first model, an outside measurement of 8
cu. ft., held 24 pints of blood, and, when packed, weighed 132
pounds.
The wire racks were so designed that the larger bottles could
easily be inserted. This container was, like the first Bailey model,
too bulky for one man to handle, and, like the first, it did not
withstand adverse weather conditions.
Hollinger container.-Containers made by the Hollinger
Corp. were put into use in October 1951, after the supply of Bailey
containers was exhausted. This container (fig. 184) was built like a
trunk. Its outside measurement was 6.4 cu. ft. and it weighed 115
pounds when fully packed. The exterior shell was of plywood covered
with laminated fiber to make it waterproof. Insulation was provided
by 2-inch slabs of Styrofoam, which were snugly fitted and attached
to the inside of the plywood shell by cement. Each of the two wire
racks held twelve 500-cc. bottles of blood, and the tin container in
the center held about 20 pounds of wet ice. Between the insulation
and the wire racks was a moisture-vapor barrier of corrugated paper.
The insulated lid of the Hollinger container was attached by
hinges, and the box could be closed and latched like a trunk or
footlocker. A strip of rubber around the rim of the box increased
its insulating properties. Metal handles
763
FIGURE 183.-Whole blood shipments arriving in Korea
in insulated cardboard Army box originally used for airlift. Note
that boxes are beginning to show signs of deterioration after
transportation and exposure. A. Arrival of blood at 6th Medical
Depot, Taegu. B. Arrival of blood at 4th Field Hospital, Taegu.
attached to the sides facilitated handling. Although it could not
be handled by one man, this box was easier to move than the
containers previously used.
The original Hollinger model was very sturdy, withstood rough
handling and bad weather conditions, and maintained the correct
temperature en route. Approximately 600 were employed, and each made
an average of 10 to 12 round trips from the Travis laboratory to
Japan.
While the original Hollinger container was still in use, another
container was obtained from this manufacturer. It was also a trunk
type, but larger (8.1 cu. ft.), heavier (133 pounds), and better
insulated than the first model. The insulating layer, which
consisted of 3 inches of Styrofoam instead of the 2 inches used in
the smaller container, was supplemented by an aluminum
moisture-vapor barrier instead of the corrugated paper barrier used
in the original model. The strip of rubber around the rim of the box
was wider.
The improvement in insulation, which amounted to less than 0.5°
F. over 36 to 40 hours, was not considered enough to compensate for
the increased size And weight of this second model. Nonetheless,
about 900 were used, each making an average of four round trips from
the Travis laboratory to Japan.
Evaluation
Of all the insulated shipping containers used at the Travis
processing laboratory, the Navy plywood container and the 6.4-cu.
ft. Hollinger trunk-type container were considered the most
practical, though the Navy container
764
FIGURE 184.-Trunk type of insulated container
developed for Army by Hollinger Corp. during Korean War. A. Closed.
B. Open, loaded with ice and blood and ready for shipment. Note that
bottles are upside-down, so that blood cells will settle in the top.
could be used for only two or three round trips against the 12 or
more trips the Hollinger container could make.
Fiberboard or V-board containers did not prove practical for
field use. They did not lend themselves to long-distance shipping,
rough handling, and adverse weather conditions, and they were good
for only a single trip. They made difficulties in FECOM, and
personnel were understandably reluctant to ship blood to forward
areas in them because they sometimes fell apart. The
765
FIGURE 185.-Refrigerated container, developed at Fort
Totten after Korean War and still in use (1962). Note ice in plastic
container in cover.
blood distribution center of the 406th Medical General Laboratory
in Tokyo had the Navy plywood container (16-pint capacity)
duplicated; most of the whole blood shipped from Japan to Korea
during the last 2 years of the war went in these boxes.
In all, about 15,000 containers were shipped from Travis Air
Force Base to Japan during the course of the war. Of the reusable
Hollinger trunk type, 1,500 were the only ones used between October
1951 and February 1954. Though some of them made as many as 12 round
trips, they were still in good condition when the program was
terminated.
One disadvantage of the Hollinger containers was that they had no
space for recipient sets. During the time they were in use,
therefore, the sets had to be packed in separate crates, which were
shipped with the containers. In all, over 350,000 recipient sets
were shipped to the Far East.
The price of insulated shipping containers ranged from $25-$30
for the Navy plywood type to $40-$50 for the Hollinger container.
Shortly after the war in Korea ended, another refrigerated
container, which is still in use (1962), was developed at Fort
Totten. This box (fig. 185) has
766
FIGURE 186.-Refrigerator units for storage of blood
at medical depot, Chunchon, Korea, December 1951.
space for 24 bottles of blood, weighs only 20 pounds loaded, and
costs only $4.80. The ice is in the plastic bag in the cover, and
the arrangement provides better insulation: In the refrigerated
container originally developed at Fort Totten, as the ice in the
center melted, the tops of the bottles of blood were left
unrefrigerated.
REFRIGERATION FACILITIES IN THE FAR EAST
Refrigeration facilities in Japan and Korea (figs. 186, 187, and
188) were generally satisfactory.
Section VI. Techniques of Preservation
PRESERVATIVE SOLUTIONS
Whole blood.-The first blood sent to the Far East from the Zone
of Interior during the Korean War was collected in the ACD formula
used during World War II, 25 cc. of which was used for each 100 cc.
of blood (p. 227). At the 23 September 1950 meeting of the Committee
on Blood and Blood Derivatives (25), on the advice of Dr.
William G. Workman, Chief, Laboratory. of Biologics Control,
National Institutes of Health, the amount of solution used was left
unchanged but the formula was altered to 2.45 gm. of dextrose; 137
gm. of U.S.P. sodium citrate, and 5 gm. of U.S.P. citric acid per
100 cc.
767
FIGURE 187.-Refrigeration facilities for blood at
Eighth U.S. Army Medical Depot, Yonhdung-Po, Korea, June 1953.
of solution. The recommended change was accepted because it was
expected that temperature controls would be less precise during the
airlift of the blood than during its storage.
Plasma.-Blood intended for plasma was usually collected in
a 4-percent trisodium citrate solution during the Korean War. When
it was collected in ACD solution, the plasma was difficult to dry,
and the quality of the product varied from lot to lot.
The question of using a single solution for the collection of
blood, no matter for what purpose it was intended, came up a number
of times in the Committee on Blood and Blood Derivatives. On 26
August 1952, the Blood Group, Department of Defense, in cooperation
with the National Research Council, American Red Cross, and National
Institutes of Health, agreed to enter upon a formal investigation of
the use of ACD solution in the prepara-
768
FIGURE 188.-Refrigerator, used in field hospitals in
Korea. The prototype of this box was available in World War II but
was never put into production. A. Closed. B. Open, showing storage
arrangement and mechanism.
769
tion of plasma. By the plan adopted, 240 units of blood collected
in the NIH ACD formula would be shipped to each of two processing
laboratories, and samples of the dried plasma produced would be sent
to NIH for routine testing. The National Research Council would
conduct the clinical investigations.
The investigation, which was not finished during the war, gave
only inconclusive results.
RED BLOOD CELL PRESERVATION
It was the consensus of the Committee on Blood and Blood
Derivatives that the crux of the problem of blood preservation was
the vitality of red blood cells. On 2 December 1949, Dr. Colin,
reporting to the Committee for the Formed Elements Group, stated
that all the evidence indicated that intact erythrocytes were
necessary if blood was to fulfill its respiratory function (23).
He thought it possible that optimum preservation might be achieved
only after separation of the red blood cells from all destructive
enzymes for which each element served as a substrate.
As time passed, the Committee on Blood and Blood Derivatives,
NRC, became more and more convinced that no very great advances
could be expected in red blood cell preservation until more basic
knowledge concerning these cells was available. The committee (now
known as the Committee on Blood and Related Problems) therefore
sponsored two symposia on the subject. The first, a Conference on
the Differential Agglutination of Erythrocytes, was held on 17
September 1952 (26), and the second, a Symposium on the
Structure and Cellular Dynamics of the Red Blood Cell, was held on
11-12 June 1953 (27).
In spite of all the work done on red blood cell preservation
before and during the Korean War, the statement made at the 4 March
1953 meeting of the Committee on Blood and Related Problems (28)
remained true until the end of the war, that the last great advance
in blood preservation was the addition of glucose to the preserving
medium. (p. 217). This addition marked the first time that the
energy of red blood cells had been taken into consideration in
attempts to preserve them. On the other hand, while the addition of
glucose was an improvement, it did not prevent cellular energy from
deteriorating during storage.
Space does not permit the account of several related conferences
held during the Korean War under the auspices of various committees
and subcommittees of the Division of Medical Sciences, National
Research Council. They included, among others, several conferences
on blood coagulation and a conference on fibrinolysis.
EXCHANGE RESINS
At the Symposium on Blood Preservation held on 2 December 1949 (23),
Dr. John G. Gibson II, Harvard University Medical School, and Dr.
Edward
770
S. Buckley, Jr., Peter Bent Brigham Hospital, reported their work
on exchange resins in the preservation of blood as follows:
Reduction of the calcium content of the blood below the critical
level will prevent blood clotting by preventing the formation of
thrombin by prothrombin, a reaction for which calcium is apparently
essential. When citrate is added to blood, a soluble calcium-citrate
complex results which does not dissociate sufficiently to provide
enough calcium for the reaction just described to occur. presumably,
other divalent ions are also "complexed" by the citrate ion. The
same principle is involved in the use of an ion-exchange resin
except that the calcium-resin complex is insoluble, as are also the
other ion complexes formed. The degree of reduction in effective
concentration may therefore be quantitated.
Collecting blood directly into a flask containing the resin did
not prove feasible. Best results were obtained when the blood was
allowed to flow through a column of resin into the collecting
vessel.
Blood collected by this technique did not clot. It showed no
significant changes in pH, freezing point, or sodium concentration.
The calcium concentration was reduced to less than 1 percent and the
potassium to about 1 milliequivalent per liter. Zinc was not removed
from either cellular or plasma components. Two in vivo canine
experiments showed a post-transfusion red blood cell survival of
approximately 90 percent.
At the conclusion of this report, Dr. Colin commented that the
most remarkable recent advance in the preservation of blood was the
introduction of an ion-exchange resin, which apparently removed not
only the calcium involved in coagulation of the blood but also some
of the metals utilized in enzyme activity. The collection of blood
over an exchange resin into a vessel without a wetting surface,
which did not contain an anticoagulant, would, however, make
necessary the determination of a new baseline regarding the optimal
environment for its formed elements. Except for a few small-scale
experiments, blood had never been studied in the absence of citrate
concentrations, which were usually quite high.
Among other reports at this same symposium was one by Dr. Charles
P. Emerson, Jr., Boston University School of Medicine, which showed
that the immediate decalcification of fresh blood by passing it
through a resin column had no immediate discernible effect on the
osmotic fragility of red blood cells. When, however, the blood thus
collected was stored, there was, as in blood stored in ACD solution,
a progressive increase in their fragility. Moreover, the magnitude
of the changes observed was considerably greater, particularly after
the 10th day, than in ACD solution. Resin-collected blood stored
less than 10 days without removal of plasma but with the addition of
a saline-dextrose diluent seemed comparable in stability to
ACD-collected blood stored without modification for a similar length
of time. Resin-collected blood stored without further modification
was essentially nonviable when transfused on the 20th day; 80
percent was eliminated from the recipient's circulating
771
blood within 10 minutes and the remainder within 48 hours. The
period of survival was essentially the same whether the pH was 7.2
or 6.8.
It was considered possibly significant that poor survival of
stored citrate-free, calcium-free blood was invariably associated
with the finding of a dextrose concentration below 100 mg. percent.
At a meeting of the Panel on Preservation of Whole Blood and Red
Cells on 28 March 1951 (29), it was agreed that none of the
studies carried out with ion-exchange resins or anything, else had
produced sufficient effects on red blood cell survival to warrant
changes in the preservative solution in use. It was urged that
testing techniques used in the various laboratories be standardized,
to facilitate comparison of results and thus aid in the evaluation
of the solutions used. Particular emphasis was placed upon the
temperature of collection and storage of the blood and upon the
rapidity of cooling.
FREEZING
The preservation of whole blood at subzero temperatures, although
it had been discussed before the Korean War, was not seriously
considered during it.
At the 2 December 1949 Symposium on Blood Preservation (23),
Dr. Max M. Strumia reported on the extensive experiments he had
conducted with this technique. From them, he concluded that optimal
preservation of whole blood for up to 2 months could be accomplished
if it were stored at 26.6° F. (-3° C.). The temperature range,
however, was relatively narrow. With a variation of more than 1.5°
C., even though the physical status of the blood remained unchanged
(that is, whether it were liquid or solid), the status of the red
blood cells showed considerable deterioration. In all of his
experiments, therefore, Dr. Strumia used the temperature of -3° C.
as optimal and kept variations within plus or minus 0.2° C. If
preliminary shrinkage of the red blood cells, which he considered
essential, was carried out by the correct technique before the blood
was frozen, the period of preservation was materially lengthened.
Cells thus shrunken returned to normal size when they were immersed
in plasma but not when they were immersed in physiologic salt or
other isotonic solutions. When the cells were used for transfusion,
they resumed their normal shape and size within an hour of the
transfusion.
The concentration of glucose in the preserving fluid when the
cells were frozen at -3° C. was found to be critical. If the level
was below 40 mg. percent, preservation was bad. If it was greater,
it was fair. If the level was below 20 mg. percent, preservation was
"terrible."
At this same meeting, Dr. Walter stated that he had been able to
reproduce Dr. Strumia's work; that his laboratory had repeated the
work on vitrification done 10 years earlier, with the same results;
namely, that approximately 50 percent of morphologically intact
erythrocytes were present after thawing. He thought that the problem
was one of thawing and that it might be a blind alley.
772
Part III. The Plasma Program
PLASMA SUPPLIES BETWEEN THE WARS
The details of the disposition of surplus plasma at the end of
World War II are related elsewhere (p. 310). In substance, all the
surplus, exclusive of certain amounts retained for Army use, was
transferred to the American Red Cross, for use by the public which
had provided it originally. The stocks transferred amounted to
960,183 250-cc. packages and 1,386,726 500-cc. packages. When the
Korean War broke out, a large part of this plasma had been utilized
by hospitals, clinics, private physicians, and research workers.
What was left had become outdated and required reprocessing, which
had been accomplished in only a small number of units.
At the end of World War II, the production facilities for plasma,
which had been established by the Federal Government through the
Defense Plants' Corp., were dismantled. Equipment was declared
surplus. A small portion was purchased by individual laboratories,
and the remainder was disposed of by public sale.
STOCKPILES AND FUTURE REQUIREMENTS
Current Stockpiles
Army and Navy inventories as of September and November, 1949,
respectively, were as follows:
1. No blood was on band except for day-by-day requirements.
2. The Army had on hand 16,695 250-cc. packages of plasma and
92,865 500-cc. packages.
3. The Navy had on hand 722,171 500-cc. packages of plasma.
4. The Army had on hand 17,869 standard packages, and 2,679
salt-poor packages, of albumin.
5. The Navy had on hand 242,194 standard packages, and 5,967
salt-poor packages, of albumin.
An Army contract with Cutter Laboratories to reprocess 40,000
packages of outdated dried plasma had gone unexpectedly well. The
percentage of loss, which was only 0.3 percent, was chiefly caused
by subjecting the material to intense heat and by failure of
proteins to go into solution when the plasma was reconstituted. The
cost of reprocessing was about a third of the cost of processing
fresh plasma obtained from voluntary donors. The National Institutes
of Health was willing to approve reprocessed plasma for 5 years. The
manufacturers thought a longer dating period was justified.
Stocks of plasma, albumin and gamma globulin on hand were
considered temporarily adequate for peacetime requirements. Most of
the plasma, however, would become outdated during 1950, and none of
it had been irradiated
773
against the hepatitis virus (p. 778). Also, some plasma would not
be satisfactory for reprocessing because of its fat content and
because of original inadequate drying. A considerable amount of
albumin and other fractions could probably be recovered from the
plasma unsuitable for reprocessing, but the remaining stocks might
not meet even peacetime needs, and replacements must be procured
from agencies participating in the national blood program.
Although there was no substitute for whole blood, as the Task
Group emphasized, it could not be stockpiled, and blood derivatives
and plasma-expanders must be stockpiled for emergencies. Research
must be pressed for better agents for replacement therapy than were
presently available.
Wartime Estimates
The March 1950 report of the Task Group (4) estimated that
in the event of war, requirements for the Zone of Interior from
M-day to M+12 (months) would be 290,000 units of blood and 510,000
500-cc. units of plasma. Oversea estimates were based on two units
of blood and two units of plasma for each thousand troops exposed to
combat, with 10 percent added for losses due to breakage and
outdating. Allowances were also made for shipping losses in the
first month, and for the needs of U.S. civilian casualties in the
combat zone.
The Task Group estimated that for wartime, at least 120,000 units
of blood would be required for shipment overseas during the first
year of combat, with increasing amounts thereafter. Transportation
of blood in wartime would require the highest priority. The
capabilities of various types of aircraft for this purpose were
estimated.
The Task Group also recommended: 1. That at least a million
500-cc. packages of plasma should be stockpiled by 1 June 1951, with
additional increments procured in yearly installments over the next
4 years. Provision should also be made for rotation of stock by
withdrawals to meet current military and civilian needs. 2. That
equipment should be stockpiled for the collection and administration
of blood and should be replaced by rotation. It was thought that
there should be no difficulty in meeting this requirement if
manufacturers were provided with the proper priorities.
PROCUREMENT OF PLASMA
Initial Planning
Since at this time there was neither a civilian nor a military
blood program in existence of sufficient scope to meet the needs of
national defense, the Task Group recommended that, as a first step
in procurement of the desired amount of plasma, existing stores of
plasma and blood derivatives be reprocessed as they became outdated
while additional plasma was being procured to bring the war reserve
for the Armed Forces up to the desired level. Along with the re-
774
sponsibility of whole blood procurement for Korea, the American
Red Cross accepted the responsibility of coordinating the collection
of blood for plasma.
In August 1950, after it complete survey of commercial
laboratories by the Industrial Mobilization Board, DOD, it tentative
production schedule was established to meet the target of a million
units of plasma by June 1951, a target that had become both more
urgent and more difficult because of the outbreak of the war in
Korea on 25 June 1950.
Government-owned plasma-processing facilities were set up at once
at, Sharp & Dohme, the Upjohn Co., and Eli Lilly and Co. Litter
contracts were made with Hyland Laboratories; Courtland
Laboratories; Cutter Laboratories; Armour Laboratories; and E. R.
Squibb and Sons. These firms, which were variously located on the
west and east coasts and in the midportion of the country, were
selected on the principle of locating commercial processing
laboratories as near to donor collecting centers as possible, since
plasma and red cells must be separated from each other within 24 to
30 hours after the blood is collected.
In October 1950, before planning had proceeded very far, it
became necessary to replace the stockpiling program because of
unexpectedly heavy demands for blood from the Far East Command, as
well as because of processing delays. The original goal of a million
units by June 1951 was halved, but even this objective could not be
met, and, by the end of the fiscal year, only 87,279 units of plasma
had been delivered. At this time, seven of the eight plants listed
were in operation. Their joint monthly capacity was 58,600 units,
and their final capacity as of April 1952 was set at 148,000 units
per month.
Procurement Difficulties
For the first 6 months of the new plasma operation, the largest
available drying capacity was in the three laboratories on the west
coast. By February 1951, the east coast laboratories had a capacity
of 10,000 packages per month, but it, was not until August 1951 that
the laboratories in the middle of the country had completed the
installation of their drying equipment. On the east coast, the
opening of bleeding centers had been set far ahead of scheduled
production, while on the west coast, the reverse was true. As a
result, blood had to be shipped to the west coast production
laboratories from the east coast bleeding centers. Shipping of blood
in ACD solution long distances by air was not desirable technically
or economically when the blood was to be used for plasma, and some
of it froze during the bitter winter weather, but this plan had to
be employed as a matter of expediency.
In January 1951, representatives of the Department of Defense and
the American Red Cross were assigned to the processing laboratories
to iron out difficulties as they arose and to take corrective action
at once. Production at one laboratory, for instance, was held up
until administrative and personnel problems were corrected by the
appointment of a new laboratory director.
775
Another laboratory was inoperative for 2 weeks because of trouble
with its shell-freezing technique.
Early in January 1952, the Department of Defense learned that the
Bureau of the Budget had allocated the funds for its 1953 plasma
reserve to Federal Civil Defense, for inclusion in its estimates for
stockpiling (2). The situation was considered at a meeting on
18 January 1952, in the Office of the Directorate, Armed Services
Medical Procurement Agency, which was attended by both military and
civilian personnel. It was agreed that the Blood Donor Program must
continue to operate at its present level (300,000 bleedings per
month) and that plasma processing facilities be used without
interruption. Two general plans were considered:
1. That a single stockpile of plasma be set up for national
defense, with both the Armed Services and Federal Civil Defense
drawing from it.
2. That Federal Civil Defense take over all control of the Blood
Donor Program when existing contracts held by the Armed Services
ran out.
Neither of these plans was desirable, but the second was
considered the more undesirable of the two: It would require
revision of the Current program; initiation of new contracts with
the American Red Cross and the plasma processing laboratories;
hiring of additional personnel; and training them in procurement,
testing, inspection, and other procedures. It would also require
deemphasizing the program for blood for Korea, which had been
generally successful, and stressing the requirements for stockpiling
for national defense, with little assurance that the new program
would be completely successful or have the same general appeal.
While these plans were being debated, a new factor entered the
picture, which could not be ignored by the Department of Defense.
This was the "alarming" percentage of hepatitis in persons who had
received plasma infusions, especially when the plasma had been
prepared from large pools (p. 674). The reprocessing of World War II
stocks of plasma had run into this problem, and the Department of
Defense wanted no reserves of that kind.
At meetings of the Armed Forces Medical Policy Council on 17
March and 28 April 1952 (2), it was agreed that, after some
satisfactory method of sterilization against the virus of hepatitis
had been found, the plasma program would be divided into two phases.
In the first, priority would be given to military and pipeline
requirements for plasma. In the second, stockpile reserves would be
accumulated. The Department of Defense wished to continue its
priority until such time as the first increment of its reserves had
been built up with plasma free from infection, after which stocks
would be divided equally between civilian and military agencies. At
a joint meeting on 16 May 1952 of the Armed Forces Medical Policy
Council and the (Cummings) Subcommittee on Blood, Health Resources
Advisory Board, the subcommittee agreed to accept the dual stockpile
plan but not the proposal that the Department of Defense build up an
increment of infection-free plasma before Federal Civil Defense
secured any plasma at all. The Department of Defense, on the
776
other hand, was entirely unwilling to use currently available
plasma, from which a comparatively large proportion of recipients
might be expected to develop infectious hepatitis. The Armed Forces
could not tolerate long periods of incapacity among its personnel,
their corresponding delay in return to duty, and a reduction in the
effective military strength of the country. All of these losses
could be better tolerated by civilian personnel than by combat
troops.
When the disagreement continued, with the Secretary of Defense
supporting the position of his Policy Council, it was agreed, on 2
June 1952, that the decision would have to be made by the President.
The allocation of plasma reserves was still undecided by the end of
the year, but had become largely academic, since no satisfactory
method of sterilization of plasma had been devised. A lack of funds
also made it impossible to meet the desired goals.
By the end of fiscal year 1952, the Federal Civil Defense
Administration had contracted for 750,000 units of plasma, none of
which had been delivered. In addition, it had not received any of
the 300,000 units of dextran and the 1.2 million units of
polyvinylpyrrolidone that had also been ordered.
SERUM HEPATITIS
The potential problem of serum hepatitis, as mentioned elsewhere
(p. 776), began to be appreciated only shortly before World War II
ended. With the end of the war, the massive use of plasma ceased,
and, in the absence of a central reporting agency, such cases of
serum hepatitis as occurred after plasma infusion did not have the
impact which they would have had in time of war and which they were
to have when the outbreak of the war in Korea required a resumption
of en masse plasma infusions.
Shortly before World War II ended, Dr. John W. Oliphant and his
associates at the National Institute of Health (30, 31) began
their work on the ultraviolet sterilization of plasma as part of its
processing (fig. 189). The first results were most encouraging, a
particularly desirable feature of the method being that the plasma
proteins were apparently unaffected by the amount of ultraviolet
energy used. Unfortunately, the belief that the problem had been
solved was to prove fallacious.
There was scarcely a meeting of the Committee on Blood and Blood
Derivatives (the reconstituted Subcommittee on Blood Substitutes),
NRC, at which serum hepatitis and attempts at sterilization of
infected plasma did not come up for discussion. Space does not
permit an extended account of these matters, and the reader is
referred to an excellent summary by Dr. Roderick Murray, Laboratory
of Biologics Control, National Institutes of Health, who took over
the work on Dr. Oliphant's death. The report which contains a
comprehensive list of references, was presented at a Conference on
Derivatives of Plasma Fractionation, on 28 October 1953 (32).
777
FIGURE 189.-Technique of plasma production during
Korean War. A. Insertion of bottles of blood into large centrifuge
to separate plasma from red blood cells. B. Pooling of plasma from
from bleeding bottles after centrifugation. C. Transfer of plasma
from pool into individual dispensing bottles. D. Shell freezing of
plasma in large bottles. E. Storage of shell-frozen plasma. F.
Ultraviolet light sterilization of plasma. This additional step was
introduced into the processing of plasma when serum hepatitis became
a serious threat.
778
Special Studies
The experience of the Armed Forces in Korea showed that, while
0.5 percent of recipients of whole blood developed hepatitis, 12
percent or more developed it after infusions of pooled plasma. In
1951, it was therefore decided to use human volunteers for testing
the infectivity of plasma and plasma derivatives and evaluating the
efficacy of various methods proposed for its sterilization (table
40).
TABLE 40. - Results of inoculation of
volunteers with serum from six suspected donors
|
Volunteers inoculated |
Interval since incriminated donation |
Hepatitis cases— |
Incubation period for— |
|
With jaundice |
Without jaundice |
Total |
Volunteers1 |
Original recipient |
|
Number
|
Days |
Number |
Number |
Number |
Days |
Days |
|
10 |
203 |
0 |
0 |
0 |
--- |
65 |
|
10 |
385 |
4 |
22 |
6 |
(18), 30, 45, 46, (46), 56 |
48 |
|
5 |
--- |
0 |
1 |
1 |
(43) |
--- |
|
10 |
356 |
1 |
20 |
1 |
48 |
40 |
|
10 |
149 |
1 |
20 |
1 |
84 |
70 |
|
10 |
135 |
4 |
0 |
4 |
35,
50, 56, 72 |
--- |
|
5 |
--- |
5 |
--- |
5 |
43,
49, 56, 57, 63 |
44 |
|
10 |
43 |
2 |
31 |
3 |
(50), 57, 67 |
32 |
1Incubation periods in
parentheses refer to cases of hepatitis without jaundice.
2One additional subject presented equivocal or abnormal
tests suggestive of hepatitis without jaundice.
3Three additional subjects presented equivocal or
abnormal tests suggestive of hepatitis without jaundice.
By the time these studies were undertaken, numerous disquieting
reports had been received indicating that hepatitis was occurring
after the use of irradiated plasma, which presumably had been
rendered safe. One such report (33) showed an incidence of
11.9 percent in patients who had been followed for at least 6 months
and most of whom had received more than one unit of plasma.
Sterilization Techniques
Ultraviolet irradiation.-Irradiation of plasma with ultraviolet
light was usually carried out by exposing a thin film of plasma to
radiation from a high intensity source (32). Various types of
equipment were used. In some, the plasma was passed through a
narrow-bore, usually flat, quartz tube resembling a hollow ribbon.
In others, the film was formed on the inside wall of a hollow
cylinder or cone which rotated at high speed and in the cavity of
which the ultraviolet lamps were located. In some of these lamps,
quartz envelopes transmitted most of the ultraviolet light. In
others, Vycor envelopes transmitted radiation only in the 2735 A.
band or higher. Apparatus of the latter type was most widely used in
the plasma-processing laboratories because of
779
its ability to handle relatively large amounts of plasma, by the
formation of films on the inner surfaces of cylinders or cones.
The NH studies on the effect of ultraviolet light on plasma were
carried out with three different machines of the type just described
(table 41). An attempt was made to simulate actual processing
conditions. Special attention was paid to the measurement of the
ultraviolet output of the lamp used, to continuous monitoring of
each irradiation run, and to accurate measurement of the rate of
flow of plasma through the apparatus. Each run was also checked by
the Aerobacter aerogenes test.
The results of this study eliminated the hope originally raised
that failure of sterilization might be due to some defect in the
apparatus or to inadequate exposure to ultraviolet irradiation. As
this experience (table 41) showed, the margin of safety between the
sterilizing dose and the dose producing unacceptable denaturation of
plasma was not sufficiently great to justify placing much reliance
on this technique. Moreover, considerable changes in plasma proteins
were apparent after sterilizing dosages that might actually produce
inadequate exposure.
TABLE 41. - Results of ultraviolet
irradiation of infected pooled plasma
|
Apparatus and conditions of irradiation |
Volunteers |
Volume of dose |
Hepatitis cases— |
Additional subjects with suggestive laboratory findings |
|
With jaundice |
Without
jaundice |
Total |
| |
Number |
ml. |
Number |
Number |
Number |
Number |
|
Dill apparatus:
|
|
|
|
|
|
|
|
515 ml./min. |
10 |
1.0 |
3 |
1 |
4 |
0 |
|
249 ml./min. |
10 |
2.0 |
2 |
1 |
3 |
1 |
|
73 ml./min. |
10 |
4.0 |
6 |
3 |
9 |
0 |
|
Control |
10 |
1.0 |
4 |
2 |
6 |
1 |
|
Habel-Sockrider apparatus:
|
|
|
|
|
|
|
|
1 passage |
10 |
1.0 |
4 |
1 |
5 |
1 |
|
5 passages |
10 |
2.0 |
0 |
0 |
0 |
0 |
|
10 passages |
10 |
4.0 |
0 |
0 |
0 |
0 |
|
Control |
10 |
1.0 |
6 |
0 |
6 |
1 |
|
Oppenheimer-Levinson
apparatus:
|
|
|
|
|
|
|
|
10" bowl, standard lamp |
8 |
1.0 |
3 |
1 |
4 |
0 |
|
15" bowl, high-powered
lamp |
8 |
1.0 |
2 |
1 |
3 |
0 |
|
Control |
5 |
1.0 |
2 |
0 |
2 |
0 |
Controlled heating.-Samples of infected pooled plasma were
subjected to controlled heating by complete immersion in constantly
agitated water at 59.2° and 60.4° C. for 2 hours and 4 hours,
respectively. Two bottles were tested for each time period, and a
fifth bottle was kept at room temperature during the heating
process. All bottles were then immediately shell frozen
780
by means of Dry Ice and alcohol and stored at -20° C. until they
were administered to volunteers. Some of the Dry Ice in which the
material was transported to the using hospitals was still present
when the flasks were opened for the inoculations.
Two groups of 10 volunteers each, who had been carefully screened
by liver function tests, were inoculated with the heated material,
and 5 others were inoculated with the control plasma. Cases of
hepatitis developed in each group (table 42).
Storage at room temperature.- Room storage temperature, which had
been developed by Dr. J. Garrott Allen and his associates at the
University of Chicago with extremely promising results (32, 34),
was evaluated in three groups of volunteers. There were three
instances of hepatitis in a group of five subjects inoculated with
plasma stored at an almost constant temperature of 70° F. for 3
months against only one instance in 20 subjects inoculated with
plasma stored at a similar temperature but for 6 months. The single
case of hepatitis in these patients occurred at the end of 196 days,
the longest incubation period on record, and was mild.
TABLE 42. - Results of heating infected
pooled plasma at 60° C.
|
Duration of heating
|
Volunteers |
Hepatitis cases—
|
Incubation period |
|
With jaundice
|
Without
jaundice |
Total |
|
Hours |
Number |
Number
|
Number |
Number |
Days |
|
2 |
10 |
3 |
11 |
4 |
70, 170,
126, 147 |
|
4 |
10 |
3 |
22 |
5 |
284,
87, 88, 291, 97 |
|
Not heated |
5 |
1 |
1 |
2 |
77, 177 |
1Clinical signs and
symptoms, no jaundice.
2Only abnormal laboratory findings.
Dr. Allen presented his own figures on plasma stored in the
liquid stage for 6 months before use: There was no instance of
hepatitis in 1,546 plasma transfusions, with a careful 6-month
followup, while over the same period there were 49 cases of
hepatitis, 0.4 percent, in 37,026 whole blood transfusions.
At this same meeting, it was reported that beta-propiolactone had
failed in experiments involving the administration of transfusion
sized (600 cc.) doses of known infected plasma treated with 3,000
mg. per liter of this agent. Cathode-ray irradiation had proved
lethal for the laboratory virus of hepatitis, but it had been given
a relatively low priority in experiments on human volunteers because
the outlook with beta-propiolactone had then been considered more
promising.
Termination of the Plasma Program
There would be little point to citing other clinical and
experimental studies with treated plasma. A great many of them were
extremely hopeful
781
up to a point. In September 1950, a distinguished clinician was
so impressed with the results apparently being obtained from
ultraviolet irradiation that he declared that "the key to the
control of homologous serum jaundice is now at hand." The blunt fact
is that hepatitis continued to follow the use of plasma, no matter
how it was treated. Complete sterilization was never achieved. All
methods failed in the end.
The crux of the matter was that the Armed Forces needed some
agent to use for resuscitation until the casualty could reach an
installation where whole blood was available. They therefore had no
choice but to take the calculated risk of using plasma, even though
it might cause hepatitis. The risk was considerable. Late in 1951,
the incidence of hepatitis after plasma transfusion reached 21
percent, in sharp contrast to the reported World War II incidence of
7.5 percent. Part of the explanation was that much of the plasma
used in Korea in the first months of the war had not been treated at
all. Moreover, different diagnostic criteria were used in the two
wars. In World War II, the diagnosis was chiefly clinical. In the
Korean War, any elevation of the serum bilirubin was considered an
indication of hepatitis.
In January 1952, the National Institutes of Health agreed that
pools of plasma should be reduced from the approximately 400 bloods
then being used to not more than 50. The change could not be made
immediately because the smaller pools required changes in equipment
and techniques.
Hepatitis continued to occur, and at the 8 October 1952 meeting
of the Subcommittee on Sterilization of Blood and Plasma, Committee
on Blood and Related Problems, it was recommended that, because of
the risk of hepatitis, plasma should be used only in emergencies and
when no plasma-expander was available (85). Otherwise, serum
albumin, which had proved to be extremely effective, or dextran,
which had been tested extensively, should be used. The reduced yield
from blood, as compared with the plasma yield (p. 342), would be
compensated for by the other desirable byproducts secured by
fractionation of plasma, and it was recommended that, as far as was
practical, the present plasma program be converted to large-scale
production of human serum albumin. Meantime, the search for
techniques of sterilizing plasma should be continued. It was brought
out, however, that when such a method was found, the sterilized
plasma would be a new item, and an extensive program of testing and
clinical evaluation would be required before it could be recommended
and standardized. Some doubt was expressed that the blood
procurement program could be sufficiently increased to provide the
extra blood needed for the production of serum albumin.
At the 4 February 1953 meeting of the Subcommittee on
Sterilization of Blood and Plasma, the third death from hepatitis in
a volunteer was reported, and the testing program was suspended by
action of the Armed Forces Epidemiological Board (36).8
It was recommended at this meeting that
8 In his report at the Conference
on Derivatives of Plasma Fractionation on 28 October 1953 (32),
Dr. Murray gratefully acknowledged the service of the volunteers
in these studies, who were secured through the cooperation of
the Bureau of Prisons, U.S. Department of Justice, and the
staffs of the U.S. Penitentiaries at Lewisburg, Pa., and McNeil
Island, Wash., and the Federal Correctional Institution,
Ashland, Ky.
782
packages of plasma prepared for clinical use carry a conspicuous
warning to physicians that, serum hepatitis could be transmitted by
plasma, in spite of ultraviolet irradiation, and also advising
careful selection of blood donors.
On 20 August 1953, Circular No. 73, Department of the Army,
directed that, because of the risk of serum hepatitis, the higher
cost, and the need to use it for the production of specific
globulins, plasma would not be used "to support blood volume" unless
dextran was not available (37).
Part IV. The Plasma Fractionation Program
SERUM ALBUMIN
When the Korean War broke out, the same reasoning that made the
Army choose plasma in preference to serum albumin as their agent of
resuscitation in World War II led them to choose it again; that is,
it took 4.2 bleedings to provide 25 gm. of serum albumin, against
only 1.2 bleedings to provide 250 cc. of plasma. Also, it was
usually necessary to supply water when serum albumin was used,
whereas the distilled water used in the reconstitution of plasma was
provided with it. Finally, the finished price of a unit of albumin
was about $20, against about $4 for a unit of plasma.
When the military reverses suffered by the U.S. Army in Korea in
the winter of 1951 increased the need for replacement substances,
50,000 units of outdated serum albumin were obtained from the Navy
and transferred to the San Francisco medical depot for shipment to
FECOM. Technically outdated serum albumin proved perfectly
satisfactory. One of its advantages was that the small size of the
units made it possible for corpsmen to load their pockets with it.
Also, serum albumin did not freeze in the bitter winter weather
encountered, as reconstituted plasma did.
When the incidence of serum hepatitis made it necessary to
discontinue the use of plasma in Korea, serum albumin was the
logical substitute. Extensive tests had shown that, when it was
heated for 10 hours at 60° C., it carried no risk of hepatitis (28,
38). Also, it could be made from contaminated plasma, which
meant that a large quantity could be obtained from the plasma on
hand and no longer considered fit for use because of the risk of
transmission of hepatitis; it was, of course, essential to use a
therapeutic replacement agent that did not cause a second pathologic
condition.
Serum albumin was readily administered in forward areas.
GLOBIN
At the meeting of the Subcommittee on Shock, Committee on
Surgery, NRC, on 11 December 1950, it was brought out that, though
globin is of great nutritive value as a protein, it was lost in 18
percent of the total protein of the blood then being discarded in
the form of red blood cells (39). It was
783
also brought out that problems connected with its clinical use,
chiefly hematuria and renal complications, had not yet been
overcome.
At the 5 April 1951 meeting of the Committee on Blood and Blood
Derivatives (40), it was reported that a modified form of
globin, prepared by Sharp & Dohme, from discarded red blood cells,
had been used by some 12 investigators to date as (1) a protein
supplement and (2) as a plasma-expander. In about a hundred trials,
there had been 10 to 15 percent of rather serious reactions, but the
processing procedure had recently been altered, and there had been
no reactions in the last 60 clinical trials.
Globin was used in 8-percent solution, in doses of about 16 gm.
daily, for patients with hypoproteinemia, caused by cirrhosis,
nephrosis, and other conditions in which there was a negative
nitrogen balance. It had been tested on only four patients in shock,
and no evidence existed that it possessed sufficient osmotic
activity to become a satisfactory plasma-expander. The trials had
not been entirely adequate because many investigators had failed to
analyze the globin per se in the bloodstream.
GAMMA GLOBULIN
A Conference on the Uses of Gamma Globulin was held oil 5 August
1952, under the chairmanship of Dr. Milton C. Winternitz (41).
Earlier in the war, there had been numerous meetings concerning this
product at the Office of Defense Mobilization, to discuss the amount
available and the anticipated needs if testing should indicate that
it was effective in preventing paralytic poliomyelitis. If it was
proved effective, the nationwide demand for it expected during the
summer of 1953 would have a tremendous impact on the blood program,
affecting every phase of it from the donation to the final product.
An ad hoc committee which had been convened by the Committee on
Blood and Related Problems to assess the situation agreed in
principle with proposals developed by the U.S. Public Health
Service. It was recommended that the National Research Council
investigate current stockpiles of gamma globulin and present
production capacities; consider production for the Armed Forces and
the civilian population and the equitable distribution of gamma
globulin between them; assess the need for, and means of, increasing
production; solicit the cooperation of both public and private
groups working on this problem; conduct, or arrange for
epidemiologic studies bearing on allocation; adopt such measures of
allocation as might be necessary and set up priorities if it was
thought that gamma globulin would be in short supply. It was also
recommended that the U.S. Public Health Service and the American
Medical Association arrange for publicity on the production and use
of gamma globulin.
Up to this time (August 1942), three field studies had been
conducted, in Provo, Utah; Houston, Tex.; and Sioux City, Iowa. It
was thought that a fourth might be necessary. Followup studies were
still incomplete, and both the potency and the dosage of gamma
globulin remained to be established.
784
Whether the ad hoc committee assumed that gamma globulin would be
only partially successful, or successful in only some cases, it had
to postulate some measure of success to make plans for the future.
It was most important to be ready to expand production capacity to
the limit as soon as possible after all field tests were completed,
by 15 October 1952.
In a second report of the ad hoc committee on the uses of gamma
globulin on 30 September 1952 (42), it was noted that the
first knowledge the National Research Council had of the possible
magnitude of the problem was at a meeting held in June 1952, with
the Subcommittee on Blood of the President's Health Resources
Advisory Committee. The Subcommittee on Blood fully recognized its
responsibility because of the possible effect a demonstration of the
preventive effect of gamma globulin in poliomyelitis might have on
the future of blood collections in the National Blood Program (p.
735) and on the allocation of blood and its derivatives between
civilian and military claimants. The present supply of gamma
globulin was inadequate. The Office of Defense Mobilization had
turned to the National Research Council for help, and the council
had noted that its role was to advise, not to implement advice. The
Office of Defense Mobilization was investigating the legal
implications connected with the situation. The provision of gamma
globulin for military dependents was, of course, an Armed Forces
responsibility.
At this time (September 1952), the American Red Cross which had
received the bulk of the surplus gamma globulin at the end of World
War II, was distributing between 700,000 and 800,000 2-cc. doses per
year for the prophylaxis of poliomyelitis and was recovering
200,000. It was then producing 70 percent of the current output and
commercial firms, 30 percent. The Red Cross was also distributing
gamma globulin for the prophylaxis of measles and of infectious
hepatitis. The Army was holding 12,000 10-cc. units and had
1,013,450 gm. in the dried state. The Federal Civil Defense
Administration had no reserves at all. On an assumed loss of 5
percent of current blood collections of 3,360,000 pints per year,
191,680 gm. of gamma globulin could be recovered.
The problem was discussed at several other meetings in 1952 and
1953 (43, 44), including a conference on Epidemiology of
Poliomyelitis (45). The end of active combat in June 1953
eliminated the need for further action on the part of the National
Research Council and the Armed Forces.
When final action was taken by the Office of Defense
Mobilization in June 1953 to terminate dried plasma contracts, in
accordance with NRC recommendations, because of the proved danger of
serum hepatitis (32), it was agreed by the Department of
Defense and the Federal Civil Defense Administration that the
program for the current fiscal year should include only
fractionation of plasma, with the production of serum albumin and
gamma ( globulin. All gamma globulin produced would be made
available to the American Red Cross and the National Foundation for
Infantile Paralysis at the cost of processing.
785
RED BLOOD CELLS
During the Korean War, as in World War II (p. 313), packed red
blood cells were used extensively in the treatment of chronic and
secondary anemias and in the preparation of anemic patients for
surgery. One of the chief advantages of this technique was that
large quantities could be injected within short periods without risk
of overloading the circulation. No in vitro tests were developed
during the Korean War to determine the viability of these cells, and
no gross or microscopic characteristics proved useful for this
purpose. The only valid criterion of their viability continued to be
a study of their survival in normal human subjects, a test that was
both difficult and cumbersome. Without a simple method for
continuous quality control, rigid standards of collecting,
processing, and storage were essential precautions.
CADAVERIC BLOOD
At the fourth meeting of the Committee on Blood and Related
Problems on 10 December 1952 (46), an inquiry was received
from the Army Research and Development Board concerning the
possibility of using cadaveric blood. The American Red Cross had
also received numerous letters on the same subject.
In response to these inquiries, Dr. Strumia reported work he had
done in this field in 1937-38. He considered only 12 of the 125
cadavers he had examined usable. He obtained much less blood than he
expected, an average of 1,500 cc. per body. It was difficult to
secure a free flow of blood, even shortly after death; the best flow
was from patients who had died of coronary occlusion. He found it
impossible to secure a satisfactory flow from the femoral vein, as
the Russians had reported, and had to enter the right auricle with a
½-inch trocar. In vitro tests were normal in all respects, but the
incidence of contamination was very high unless the blood was drawn
within 6 hours of death.
Dr. Strumia had not used cadaveric blood clinically, and it was
the consensus of the committee that there would be strong esthetic
objections to it by both physicians and patients in the United
States. It was also pointed out that there was no need for the use
of this method for the Armed Forces at this time since the country
was still far from exhausting its donor supply.
Part V. The Plasma-Expanders Program
BIBLIOGRAPHY
It is not the function of this history to go beyond the important
historical facts in the study of plasma expanders (the so-called
blood substitutes of World War II). Attention should be called,
however, to the excellent bibliog-
786
raphy on plasma expanders (except those derived from human blood)
prepared in the reference division of the Army Medical Library (now
the, National Library of Medicine) in December 1951 (47).
This is a most useful list. The references under each major item are
grouped according to subheadings; the number of references in each
article is stated; and the substance of the article is summarized in
one or more succinct sentences.
The need for such a reference list was pointed out in the
preface: The treatment of shock was then (1951) the most pressing
single medicomilitary emergency. It was urgent both militarily arid
in the event of a thermonuclear war in which civilians would be
involved. Since the prolonged storage of whole blood is not
feasible, realism required that two facts be faced, (1) that it
would be completely impractical to secure blood from donors in the
event of a thermonuclear attack, and (2) that potential donors might
well themselves be victims of the attack and therefore candidates
for blood. The solution of the military and civilian problem was the
development of plasma, volume expanders and their stockpiling. This
collective bibliography was a useful first step in such a task.
GELATIN AND OXYPOLYGELATIN
The extensive studies made on gelatin during World War II under
the auspices of the National Research Council (p. 373) were resumed
early in the Korean War. Then, as in World War II, the major
objection to gelatin from the military standpoint was that it gelled
at about room temperature. It therefore could not be used in the
field, and even in hospitals, its use furnished some problems, which
would be intensified if bombing or some other catastrophe
interrupted electricity and heat.
Some observers believed, in view of the nature of the emergency,
that gelatin manufacturers should be encouraged to begin production
at once, even if the material might not be precisely what was wanted
(39). The proposal that 30 gm. of urea be added to each 500
cc. of gelatin to keep it liquid was considered ingenious, but
unsafe unless there could first be assurance that the recipient's
urea clearance was normal (48). Such a specification was
clearly impractical. Moreover, renal function was often sharply
reduced in combat casualties, and if they were given gelatin
infusions in the amount of 1,000 to 1,500 cc. in the course of a few
hours, they would also receive 60-90 gm. of urea, which was
obviously undesirable.
At the 14 October 1950 meeting of the Committee on Shock (49),
Dr. Ravdin reported on an oxypolygelatin of superior quality which
had been prepared in his laboratory. It did not gel at ordinary
temperatures, but it gave rise to toxic reactions closely resembling
certain reactions to oxalic acid, and he was not prepared to
recommend it at this time. A year later, it was still impossible to
obtain production of oxypolygelatins of uniform quality. Moreover,
the amounts and rates of excretion varied from laboratory to
laboratory, one probable reason being the variety of analytic
methods in use.
787
In February 1953, the outlook was even more discouraging (50).
Oxvpolygelatin had proved to be antigenic. Its retention in the
bloodstream in normotensive patients as well as in bled patients was
poorer than that of dextrall or Periston (polyvinylpyrrolidone). If
its melting point were lowered by further degradation, its molecular
weight would also be so lowered that it would not remain in the
circulation long enough to have any effect at all. Moreover, the
high initial elevation of the plasma volume achieved by gelatin
preparations, followed by the rapid loss of the osmotically active
material, might, throw a patient in shock into it very dangerous
state. In fact, if hemorrhage were also present, he would be in real
jeopardy unless he were given blood or a more effective
plasma-expander than gelatin.
It had been brought out, at one of the earlier meetings of the
Committee on Blood and Related Problems (49), that gelatin,
like other blood substitutes proposed up to that time, lacked the
capacity, essential in the management of shock, to transport oxygen.
It was also brought out at this meeting that the Armed Forces must
not assume that funds were unlimited for studies in all areas. On
the contrary, the field must be narrowed to agents of reasonable
cost, suitable for stockpiling, whose production could be expedited.
In view of these criteria, it seemed to many members of the
committee that further investigation of gelatin was not warranted.
In March 1953, it was reported to the Subcommittee on Shock that
fluid gelatin had been sent to Korea for a field trial, and it was
believed that reports on it would be favorable, since it had been
shown to restore blood volume for brief periods (51). On the
other hand, the committee noted that, if not more than 35 percent of
the blood volume had been lost and if hemorrhage did not continue,
the normal homeostatic mechanisms of the body would tend to maintain
the restoration, in which gelatin would play no part.
It was decided at this meeting that the investigation of gelatin
and oxypolygelatin should be discontinued until a product could be
supplied that could be characterized physicochemically; with
evidence of reproducibility and stability; and of higher molecular
size, so that it would not be excreted at an excessive rate, as were
the products then in use. Data on tolerance and toxicity in animals
were also desired.
No further reports on gelatin and gelatin products were made to
NRC committees during the Korean War.
POLYVINYLPYRROLIDONE (PERISTON, PVP)
Historical Note
Knowledge of polyvinylpyrrolidone, the plasma-expander more
commonly known as Periston or PVP, reached the United States during
1943. The Subcommittee on Blood Substitutes conducted a brief
investigation on it (p. 380), but it was not used in the U.S. Army
during World War II.
788
This agent was developed in Germany in 1940, when the need was
recognized for a colloidal solution for the emergency treatment of
shock (52). It was selected from some 30 compounds studied
at I. G. Farben Laboratories. When the choice fell upon polyvinyl
esters, polyvinyl alcohol polymers were first tested but were
discarded when it was found that bone-marrow depression occurred
after their repeated injection. When polyvinylpyrrolidone was
synthesized from acetylene and ammonia, the polymers formed had
molecular weights as high as 150,000 to 200,000.
According to the Germans, whose investigative methods were not
considered entirely satisfactory, about 20 percent of Periston was
excreted in the urine in the first 3 days. The remaining 80 percent
was thought to be phagocytosed after 24 hours, stored in the
reticuloendothelial system, and then probably slowly excreted,
perhaps in the bile. Qualitative tests indicated that some Periston
remained in the tissues for several weeks after injection.
Development in the United States
Periston was first considered in the Subcommittee on Shock on 14
October 1950 (49). Although it had been widely used in
Germany during World War II and about half a million cases had since
been followed up, not much was known about its use in recent years.
Apparently, it caused no lasting damage to the tissues, but no
definitive data were available on its course in the body and on the
amount that could be tolerated without deposition in the tissues.
Some members of the committee considered it worthless. Others took
the position that if it had any deleterious effects, they would have
been evident, even in the absence of expert observation, because of
the large number of cases in which it had been used.
At the 11 December 1950 meeting of the Subcommittee on Shock (39),
it was learned that the Schenley Corp. could then import 5,000 to
10,000 bottles of Periston per month from Germany and by July 1951
expected to import an intermediate form that could be processed
further in the United States. Other manufacturers were also able to
produce Periston.
The Subcommittee on Shock met with the manufacturers and
potential manufacturers of Periston on 4 January 1951 (53). A
research project had been approved in principle, but, up to this
time, no funds had been assigned for it (54). Some companies
were making Periston that very closely resembled the German product,
but they stated that their progress would be faster if the Army
would reach a decision concerning its use. The Food and Drug
Administration was prepared to clear Periston as soon as the
National Research Council furnished precise data about it and
recommended it. The point was again made that the hundreds of
thousands of cases in which it had been used in Germany, plus a
favorable report made on it by Dr. J. A. Walker, University of
Pennsylvania, furnished sufficient basis for recommending it without
much further investigation. The Department of Defense, of course,
was not in-
789
terested in putting money into material coming from a source in
which resupply was not certain.
At a meeting of the Subcommittee on Shock on 26 September 1951 (55),
another study that had been made in Germany was reported. It had
showed no deleterious effects, but it was not adequate by United
States standards: Pathologic practices were different. Records were
not precisely kept. Sections were not studied carefully, and were
not preserved.
Late in 1952, the Subcommittee on Shock recommended that
Periston produced according to certain specifications should be
stockpiled by the Federal Civil Defense Administration but should be
used only in emergencies (56). Other recommendations were
withheld until the long-term followup studies then in progress had
been completed and a more closely fractioned product of suitable
molecular weight had become available and been tested. The
effectiveness of Periston had been clearly established, but it was
stored in the body for undesirably long periods. Followup studies on
German children showed no effect on hepatic and renal function, and
post mortem studies made up to 14 months after its injection
revealed no abnormalities, but the sense of the committee was that
the burden of proof still rested on those who claimed that Periston
was perfectly safe.
At the February 1953 meeting of the Panel on Plasma Volume
Expanders (50), data were reported on 48 German children
which brought the total studied to 68. All had been treated with
Periston between 1944 and 1948, and none of them showed any
abnormalities.
Special Studies
At the meeting just mentioned, Dr. Robert M. Zollinger reported
a number of special studies on Periston made in his clinic. All
tests were within normal range except that bone abnormalities were
observed in 2 (of 18) examinations made on 14 patients. He and his
associates were unwilling at this time to attribute these
abnormalities to Periston.
Radioactive studies showed that from 95 to 100 percent of
injected Periston was excreted via the urine within 72 hours; 40
percent was excreted within 20 minutes. Within 6 hours, virtually
all circulating PVP had disappeared from the plasma. Excretion was
thus too rapid for Periston to be of value, and it was recommended
that general approval of it should be withheld, though again it was
given limited approval for stockpiling for use in emergencies if
serum albumin and dextran were not available.
On 3 March 1953, a panel discussion at a meeting of the
Subcommittee on Shock brought out the following points (51):
1. Material found in many tissues, after study by various
stains, was considered to be Periston or a reaction induced by
it.
2. Similar deposits were present in Kupffer and liver cells 14
months after injection.
3. The bone marrow changes just referred to were again present.
4. Abnormal mitoses were observed in embryonic cells grown in
tissue cultures in media containing PVP.
790
5. The anatomic and functional changes noted were mild, but
it was thought that their investigation must be pursued over
longer periods of time. It was therefore not possible to approve
Periston for any but limited stockpiling. It could not be
approved for general use.
At a meeting of the Committee on Blood and Related Problems, also
in March 1953 (28), radioautographs were reported on patients
who had been given K-30 Periston for 1 or 2 weeks before death.
After a year's exposure, the tissues showed no concentration greater
than twice what would be expected from uniform distribution in any
tissues; the accuracy of this technique did not go beyond this
level. Other studies showed that the goals of complete elimination
of PNT from the body and adequate plasma volume expansion by its use
were not mutually compatible.
At the meeting of the Subcommittee on Shock on 20 May 1953 (57),
it was reported that large amounts of Periston had been stockpiled
by the Government, but further studies were still considered
necessary before it could be recommended for any but emergency use.
The Korean War ended before further action was taken on it.
DEXTRAN
Dextran came to the attention of the Subcommittee on Blood
Substitutes, NRC, shortly before World War II ended (p. 381), but no
action was taken on it at that time. Some experimental work was done
on it in Army hospital laboratories after the war, but it had not
been used clinically in the United States when a request for
information about it was received from the Food and Drug
Administration at the meeting of the Committee on Blood and Blood
Derivatives on 3 December 1949 (8), in connection with an
application for its import from a Swedish company (Pharmacia).
Composition and Properties
Dextran was developed in Sweden during the early part of World
War II and refined to the point at which it found wide clinical
acceptance in Scandinavian countries (58). It was made up of
a variety of polysaccharides of varying molecular sizes (59).
Its production was quite simple. The only materials needed were
sucrose and an organic solvent. Fermentation required only a day,
and fractionation was not complicated. The chief bottleneck in
production was the elimination of pyrogens and testing for
sterility.
Smaller molecules of dextran were rapidly lost from the
bloodstream, a matter of importance in military medicine, in which a
considerable time might elapse between infusions. About half of each
dose was accounted for by excretion through the kidneys or the
intestinal tract. The fate of the remainder was unknown when the
Committee on Blood and Blood Derivatives began to investigate
dextran, but it was thought that the larger molecules were probably
791
deposited in the reticuloendothelial system and that they might
be nephrotoxic or hepatotoxic.
The committee, remembering that periods of 5 to 15 years had
elapsed before it was found that gum acacia could lead to amylold
degeneration, understandably took the position that great, caution
should be exercised in recommending dextran: macromolecular
substances of this type were known to cause rapid sedimentation of
red blood cells as well as a tendency to sludging. It was necessary
to consider whether dextran might give rise to breakdown products of
hemoglobin, which might be nephrotoxic or hepatotoxic. Finally, it
was necessary to investigate the maximum safe dosage and over what
period this dosage could safely be administered.
Because of the commercial situation in Sweden, it was difficult
to obtain pertinent chemical data on dextran (49), and the
British, who were also manufacturing it, did not have the desired
information. The only data on molecular size were based on viscosity
measurement. Moreover, the clinical studies conducted in Europe had
not been carried out with the precision used in such studies in the
United States.
Another reason for caution on the part of the Committee was
pointed out by Col. (later Brig. Gen.) John R. Wood, MC, at the
October 1950 meeting of the Subcommittee on Shock (49): The
implications of the decision to use dextran for combat and other
casualties would, he pointed out, be far reaching. The adoption of
any new technique would commit thousands of medical officers to it,
and the recommendation of the Committee would probably be followed
also by the civil defense organizations.
Experimental and Clinical Studies
Up to September 1950, the British experience with dextran covered
10,000 540-ml. bottles (25). No untoward effects had been
observed, but the rate of excretion via the kidneys had varied
widely, from 10 to 50 percent. At the end of 9 months, no dextran
had been found in the bodies of rabbits except for slight traces in
the lymph nodes and bone marrow. There was no histologic evidence of
tissue damage. It was believed that the chief production problem was
ridding the dextran of the small molecule, to reduce the rate of
excretion.
Up to December 1950, the Swedish experience with dextran had
covered 200,000 cases (39). In the 10 years of its use, there
had been no post mortem evidence of tissue damage, and reactions
were fewer than with the use of either blood or plasma. A
compilation of articles from the literature by Pharmacia showed an
impressive use of dextran by reliable investigators in Denmark,
Finland, and Holland as well as in Sweden.
Between 24 and 69 percent of Swedish-produced dextran was
excreted within 24 hours. Its molecular weight ranged from 120,000
to 200,000, against 80,000 to 100,000 for the British product.
Swedish dextran was now fairly uniform.
792
Clinical testing, in the United States during 1950 produced the
following data:
1. Dextran expands plasma volume in the normovolemic
individual, and return to the normal level takes a surprisingly
long time.
2. In shocked patients, many factors operate to expedite the
return of circulatory dynamics to normal. Once normal balance is
restored, the body helps to maintain it.
3. A fairly sharp discrimination is exercised by the kidneys,
based on molecular size, but the exact size at which excretion
occurs varies from person to person. In clinical use, there is
no diuresis (as there is experimentally when the smaller
molecules are removed), and the excretion of dextran is
comparable to the amount of the injection.
At a meeting of the Subcommittee on Shock on 30 January 1951 (52),
it was reported that another review of the literature had shown no
clinically undesirable renal, hepatic, hematologic, or circulatory
changes after the use of dextran. Hemodilution was maintained for at
least 6 hours after injection. Between 30 and 50 percent of the
injected material was excreted in the urine, but the fate of the
remainder was still unknown.
At this meeting a number of clinical reports were made, all to
the effect that dextran was of great temporary value. Dr. John S.
Lundy, who had had some anaphylactoid reactions with dextran when
the material was imported from Sweden and bottled in the United
States, had had no difficulty with the total Swedish product.
The single adverse report at this meeting, and at several
subsequent meetings, came from Lt. Col. Edwin J. Pulaski, MC, and
his group at Brooke General Hospital, San Antonio, Tex., who
reported 26 reactions in 105 patients (48, 52, 60), all after
the use of Swedish and British dextran. Some of the reactions had
been quite severe. A breakdown of the cases showed that four
reactions had occurred in 45 anesthetized patients. Seven different
lots of Swedish dextran had been used. There were no reactions in
patients treated with U.S.-produced dextran, which was now
available.
Thirteen ambulatory patients, chiefly Korean veterans,
hospitalized at the Forest Glen Section of Walter Reed General
Hospital, were given 500-cc. injections of Swedish dextran
(Macrodex). All but three had reactions, three of which were
moderately severe. The experiment was not considered conclusive.
There were no controls, and the patients, who were an in the same
ward, were watched over by too many observers amid too much
commotion.
Later in the year, 10 volunteers at Brooke General Hospital were
studied with fractionated material from a lot of Swedish dextran (55).
The observations suggested that the reactions which occurred must be
explained by factors other than high molecular weights or aggregates
of molecules.
At a Conference on Radioactive Dextran held on 29 August 1951 (61),
under the chairmanship of Dr. Ravdin, it was reported that the most
precise chemical analyses of excreted dextran had accounted for only
50 percent of the amount injected; all excretion was via the urine.
Dextran tagged with
793
radioactive carbon, prepared by Commercial Solvents Corp., in
cooperation with the Argonne National Laboratory, had been
distributed to it number of investigators, whose results suggested
that 95 percent of the injected material would be either excreted or
metabolized. Although the combined studies were limited both in
number (three dogs, six rats, four mice) and time (10 days), it was
decided to test radioactive dextran clinically without further
delay.
At the 13 February 1952 meeting of the Subcommittee on Shock (62),
an ad hoc committee, appointed in December 1951, reported that there
was no doubt that dextran was antigenic in man and could produce
precipitins and skin sensitivity, with the degree of sensitivity
apparently unrelated to the occurrence of systemic reactions. All
the reactions had occurred in first injections; none had been
observed in a limited number of second injections. Immunization
apparently played a negative role. Preparations of higher molecular
weight seemed to cause more systemic reactions than those of lower
weight and also precipitated more antibodies in sensitive subjects (63).
While the studies reported were still incomplete, it seemed to
the conferees to be desirable, to minimize reactions, to avoid
highly branched dextrans and preparations of high molecular weight.
No doubt was felt that reactions to dextran could be extremely
dangerous if they occurred in battalion aid stations, where medical
supervision might be inadequate. Later, it was recommended that a
warning be placed on bottles of dextran that if an anaphylactoid
reaction developed, the infusion must be stopped at once and active
treatment instituted (64).
At the 1 October 1952 meeting of the Subcommittee on Shock, it
was reported that 125 units of dextran had been used in Korea, with
good clinical results and no significant reactions (56). A
6-month study had been started in Air Force installations in the
United States.
At an ad hoc meeting on dextran fractions on 8 December 1952 (68),
it was reported that a fairly large proportion of normal, healthy
adults had experienced allergic-type reactions after the use of both
British and Swedish dextrans but that the rate with the United
States products was very low. It was now possible to define the best
possible dextran for mass production. Determination of molecular
weight was now quite accurate, and refined analytic methods made it
possible to detect even small quantities of dextran in plasma or
urine.
Studies on dextran were conducted in Korea in July and August
1952, by members of the surgical research team, on the ground that
it was not possible to duplicate total combat situations in the
wards and operating rooms of civilian hospitals, or even military
hospitals, in the Zone of Interior (65).
During this investigation, 200 500-cc. units of 6 percent dextran
were used on 60 patients, 3 suffering from burns and the others from
trauma of varying degrees. The total clinical response was
excellent. The blood pressure response was most satisfactory. The
hematocrit showed a decrease, which was maintained. There were no
allergic reactions. One patient received 2,500 cc. of dextran
solution in a single day with no ill effects. No
794
abnormalities were observed at autopsy in the three patients who
died. The best tribute to dextran was that the medical officers who
used it were uniformly eager for more.
Dextran was used in increasing amounts until the end of' the
Korean War. To complete the record, one postwar matter should be
mentioned: In September 1953, a hitherto undescribed consequence of
dextran injections was reported, a prolongation of the bleeding
time, (66, 67). It had occurred in 2 normal subjects at
Walter Reed General Hospital, and in 11 other normal subjects
observed elsewhere; the product of four manufacturers was involved.
These observations were confirmed by a study of 121 normal subjects
at Bolling Air Force Base.
The change in the bleeding time occurred within 3 to 9 hours
after the dextran had been given. There was usually a return to
normal level within 9-4 hours. The amount of dextran that had
produced the alteration ranged from 500 cc. in a single dose to
6,500 cc. over a 5-day period. There was no correlation between the
maximum prolongation of bleeding time and the maximum expansion of
plasma volume.
Recommendation and Production
At one of the first meetings after the outbreak of the Korean War
at which dextran was discussed (25), Dr. Ravdin emphasized
that in the emergency that existed, this product must be
investigated promptly as well as thoroughly. He also stated that the
Armed Forces must not rely on commercial firms to provide
specifications and standardization.
The first contract for the production of dextran was set up with
the Commercial Solvents Corp. (54). In December 1950, this
firm reported that it was negotiating with Pharmacia to manufacture
dextran under its patents (39). The Schenley Corp., which was
also producing dextran, had a similar agreement with a British
company. Meantime, Pharmacia had already licensed Refined Syrups and
Sugars Corp., whose product would probably be bottled by the Abbott
and Cutter Laboratories. The American Sugar Refining Co. was working
on a new fractionation method which did not require alcohol and
which might prove of great value if alcohol should become in short
supply. At the meeting at which these details were reported
(Subcommittee on Shock, 11 December 1950), it was recommended that
the Department of Defense begin to procure dextran that would meet
British and Swedish specifications (39).
Encouraging reports on present and anticipated production were
made at a conference on 19 December 1950, under the auspices of the
Subcommittee on Shock, which was attended by manufacturers of
dextran, including a representative of Pharmacia, drug firms, and
other interested parties (68). At this meeting the
subcommittee recommended that all dextran produced be labeled For
Stocking for Emergency Use.
795
During the following month, arrangements were made to purchase
50,000 units of Swedish dextran for the Armed Forces, to bridge the
gap while U.S. manufacturers were getting into mass production (69).
By the end of 1951, the National Research Council approved the
stockpiling of U.S.-produced dextran and the Department of Defense
entered into a contract for its production with Commercial Solvents
Corp., Terre Haute, Ind. (2). Delivery was delayed because of
the necessity of developing large-scale production facilities.
In April 1952, the Medical Policy Council directed that
commitments for the procurement of Periston be canceled and the
funds allocated to it be diverted to the procurement of additional
quantities of dextran (2). By this time, the risk of
hepatitis in the use of plasma was fully appreciated.
By the end of September 1952, Commercial Solvents Corp. had
delivered 28,588 of the 810,000 units of dextran contracted for. The
other three companies with which contracts had been made later had
not yet produced anything, but their facilities were about completed
and their potential was 3,060,000 units.
Early in 1953, dextran was approved by the Food and Drug
Administration, and a larger proportion of the stockpile was set up
with it, though the proportion between synthetic and natural
plasma-expanders was deliberately kept in balance. Later in the
year, the manufacturers made it clear that they were losing interest
in the production of dextran, in the absence of definite commitments
for its use by military and civilian agencies (67). The
concern of the Subcommittee on Shock at this development was duly
transmitted to the Office of Defense Mobilization and the Assistant
Secretary of Defense for Medical Affairs.
Plastic equipment.-The first attempt to put dextran up in
plastic bags was a failure (51). Vapor transfer through the
plastic was so great that the dextran crystallized out in the
recipient tube. A later attempt was successful (57). The
bags, which were tested in Korea and in certain U.S. hospitals,
could withstand sterilization temperatures, and long-term storage
was apparently possible; they were tested at 60° C., considered
equivalent to 2½ years' storage at room temperature. The vapor
transfer problem was settled by the use of an aluminum foil barrier.
FAT EMULSIONS
Two ad hoc Conferences on Fat Emulsions for Intravenous
Administration were held during the Korean War, on 24 May 1951 (70)
and 19 March 1953 (71). By the time the war broke out, these
emulsions had been used extensively enough to establish their
clinical value, and it was believed that there was a real need for
them to maintain caloric intake in seriously ill and wounded
patients. It was true that less than 5 percent of these patients
would need
796
parenteral fat. On the other hand, their needs might be urgent.
In Korea, the most imperative nutritional problems were encountered
in seriously wounded patients with renal dysfunction and oliguria,
in whom it was necessary to limit fluids to 500 cc. per day for
about 10 days. During this period, these casualties often lost as
much as 45 gm. of nitrogen per day, which was the equivalent of a
total 25-pound loss of muscle weight. Wound healing was slow, edema
was frequent, and the incidence of wound dehiscence was abnormally
high. The desideratum, not yet achieved, was for the development of
a pyrogen-free emulsion which would provide from 2,000 to 4,000
calories per day by parenteral administration, in as small a fluid
volume as possible.
At the second of these ad hoc conferences, as at the first, there
were two chief problems (1) the pyrogenicity of the preparations
then available, and (2) their instability. Commercial preparation of
consistently safe and satisfactory emulsions could not be expected
until a solution was found for these problems. Some of the
participants in the discussion thought that if only a fraction of
the funds expended in the development of plasma extenders were
allotted to this project, results would be prompt and beneficial,
but no such allocation was made during the war.
Part VI. Clinical Considerations
THERAPEUTIC PRINCIPLES AND
PRACTICES
General Considerations
The principles and practices governing the use of plasma (fig.
190) and albumin (fig. 191) were essentially the same in the Korean
War as in World War II. The administration of whole blood also
followed the same pattern (figs. 192, 193, 194, and 195) except that
intra-arterial transfusion was given a trial.
Intra-Arterial Transfusion
Historical note.-According to Lewisohn (72), the
first recommendation for intra-arterial transfusion, by Huerter in
1871, contained the report of eight cases in which defibrinated
blood was injected by this route.. Not much more work was done on
the subject until 1937, when Davis (73) showed, in a study of
experimental shock, that the intra-arterial injection of sodium
chloride solution elevated the blood pressure but that a similar
solution, given intravenously, lowered it. Kendrick and Wakim (74)
confirmed these observations in dogs in 1939. They also demonstrated
that the intra-arterial administration of physiologic salt solution
is not a desirable emergency treatment for secondary shock. In spite
of the immediate vasopressor response and the maintenance of the
elevated blood pressure for a certain period of time, the end result
was always severe injury to the recipient.
797
FIGURE 190.-Administration of plasma in Korea. A.
Company aidmen bringing in casualty from combat area forward of
machinegun emplacements. Plasma has not yet been started. B. Plasma
transfusion during jeep transportation of casualty to hospital,
September 1950. C. Continuing administration of plasma to casualty
as he is put aboard plane at Taejon Air Base, en route to Itazuke,
Japan, July 1950. This particular plane was one of the last to leave
the airstrip. D. Continuation of plasma transfusion as seriously
wounded U.S. soldier is unloaded from observation plane (L-5),
converted to use as one-casualty air ambulance, and moved to
conventional ambulance, 2d Infantry Division Airstrip, Korea, August
1950.
798
FIGURE 191.-Administration of albumin in Korea. A.
Preparation of albumin for treatment of casualty, 45th U.S. Infantry
Division, near Chorwon, June 1952. B. Administration of albumin to
casualty, Model Aid Station, 7th U.S. Infantry Division, preparatory
to further evacuation by helicopter, Kunwha, July 1952.
799
FIGURE 192.-Withdrawal of blood from storage for use
at 8076th Army Surgical Hospital, Kuna-ri, Korea, November 1950.
Field studies.-During the Korean War, Maj. Curtis P. Artz,
MC, Capt. Yoshio Sako, MC, and Capt. Alvin W. Bronwell, MC, treated
eight casualties by the intra-arterial route, the largest amount
given being 4,500 cc. of blood (75). The surgeon held the
needle in the artery during the transfusion, which was discontinued
as soon as the systolic pressure reached 100 mm. Hg.
One of the eight casualties died on the operating table, and
three others died within 3½ hours of operation. Although the other
four recovered, it was the impression of these observers that
casualties given blood by this route showed no appreciably improved
response as compared with patients who received blood at a
comparable rate under pressure or in multiple veins (fig. 195). One
of their patients, for instance, who was almost moribund, recovered
after being given 5,500 cc. of blood into two veins through 15-gage
needles in 30 minutes; 3,500 cc. of blood was pumped into one vein
in 21 minutes.
Experimental studies by Major Artz and his group also failed to
indicate any superiority of the intra-arterial over the intravenous
route. Since the experimental data coincided with clinical
impressions derived from the small groups of cases just described,
this method of administration was discontinued in favor of rapid
intravenous injection of blood through multiple large-gage needles
or intravenous cannulas.
800
FIGURE 193.-Administration of blood in Korea. A. Near
Uijong, April 1951. B. Before evacuation to battalion aid station
behind front-lines. C. On pod of helicopter during evacuation from
44th General Hospital, October 1953.
Conclusions.-Intra-arterial transfusion was discussed in
detail at a conference at Walter Reed Army Medical Center on 11 June
1953 (76). It was found, in extensive experimental studies,
that there was no significant difference in survival rates in
experimental and control series, and no significant difference in
the effectiveness of intra-arterial and intravenous administration
of blood. All studies pointed to the conclusion that it was the rate
of transfusion, not the route, that was the important factor.
In the general discussion that followed this presentation, Brig.
Gen. Sam F. Seeley, then Chief of Surgery, Walter Reed General
Hospital, stated that, provided that an adequate amount of blood was
given rapidly, the technique of transfusion probably made little
difference as long as cardiac action was still present. In deep
shock, it was often mechanically difficult to introduce blood
801
FIGURE 194.-Transfusion during surgery in Korea. A.
In course of amputation at 8063d Mobile Army Surgical Hospital
supporting I Corps, November 1950. B. During another operation, same
time and place.
into a vein, but always quite easy to make a femoral arterial
puncture. He also pointed out that a certain number of casualties
could be expected to die from the severity of their injuries, even
if they received preferential intra-arterial transfusion.
Other participants in the discussion took the position that
intra-arterial transfusion is an extremely dangerous technique;
cases were cited in which complete gangrene of the hand, requiring
amputation, had followed its use (72). Others, however, in
spite of the risk of ischemia, believed that in strictly qualified
circumstances intra-arterial transfusion might be justified.
802
FIGURE 195.-Rapid administration of blood to
seriously wounded casualty at forward aid station after evacuation
from Old Baldy, August 1952.
INVESTIGATIONS
Surgical
Research Team
The request of the World War II Subcommittee on Blood
Substitutes, Division of Medical Sciences, NRC, to send a team of
observers to oversea theaters was never granted (p. 79). The
question of sending such a team to Korea was brought up at the
second meeting of the Subcommittee on Shock, Committee on Surgery,
on 2 November 1950 (54), and several times thereafter until
such a team was sent to the Far East in December 1951 (65).
The
803
9 December 1952 meeting of the subcommittee was devoted chiefly
to progress reports from the team (64).
The Surgical Research Team was organized by the Army Medical
Service Graduate School and the Army Medical Research and
Development Board, which appointed personnel, set policies,
established techniques, provided consultants, and furnished
nonstandard supplies.
In Japan, the team was attached to the Far East Research Unit
(406th Medical General Laboratory) in Tokyo for administrative
purposes. Here, additional personnel, including consultants, were
provided, and supplies available on the Japanese market were
obtained. In Korea, the team was attached to the 11th Evacuation
Hospital and the 8209th MASH (Mobile Army Surgical Hospital) for
standard supplies, day-by-day assistance, and the provision of
clinical opportunities.
The principal problems related to blood which were encountered by
the team were as follows:
1. During resuscitation, problems associated with the blood
bank, the utilization of plasma, and the resulting high rate of
homologous serum jaundice.
2. During operation, abdominal hemorrhage and vascular injuries.
3. Sequelae of trauma, including secondary hypotension,
posttraumatic anuria, and infections.
The special studies on blood were made by Lt. Col. William H.
Crosby, MC; Capt. John M. Howard, MC; and Lt. Col. Joseph H.
Akeroyd, MSC (77-79).
Essential Data
General considerations.-When the Surgical Research Team reached
the Far East in December 1951, it found blood plentiful in U.S. Army
hospitals, as it had been all during the past year. The only blood
available in ROK Army hospitals was the amounts occasionally
provided by U.S. units (p. 803). The O blood used was now available
between 12 and 14 days after collection, instead of 21 to 28 days as
originally. Massive and repeated transfusions were given with few
reactions, and there were no records of deaths attributable to the
use of blood.
A special investigation showed that transportation of blood over
the thousands of miles between the United States and Korea had only
minor effects on it. Generally, it arrived at forward hospitals in
an excellent state of preservation. In 300 pints examined at random,
it was found that less than a quarter of 1 percent of the red blood
cells had been lost, and, when the blood was transfused, few red
cells were found nonviable. The plasma hemoglobin rose from about 50
mg. percent on the 10th day after collection to 100 mg. percent on
the 28th day. Harmful amounts of hemoglobin were not released into
the recipient's plasma from the transfused blood. Abnormally high
plasma potassium was not encountered during or after massive
transfusions unless renal failure was also present. The plasma
potassium level of bottled blood was apparently a straight line
function of time, the concentration increasing at the
804
rate of approximately 1 milliequivalent per day. The osmotic
fragility of the red cells showed few changes during the first 2
weeks after collection. Then it rose sharply, suggesting the
desirability, whenever practical, of using blood within the first 14
days after it had been drawn. All the evidence indicated that the
use of properly stored blood had only beneficial effects; few if any
deleterious effects were observed even when as much as 20 to 30
pints were given in less than 6 hours.
Continuous refrigeration, at temperatures of 0° to 10° C., was
absolutely essential to the safe preservation of blood. If
refrigeration were omitted, even for brief periods, irreversible
changes occurred in the red cells. They might not hemolyze
spontaneously in the bottle, but they did not survive after
transfusion.
Reactions and sequelae.-Reactions were remarkably
infrequent. In 1,620 transfusions observed at the 46th Army Surgical
Hospital (8209th MASH), there were only four urticarial reactions
and no reactions due to incompatibility. Several hemoclastic
reactions were considered as caused by gross contamination of the
bloodstream from the sites of wounds or from the peritoneal cavity.
The practice of using O blood for massive transfusions of non-O
recipients did not seem harmful provided that so-called dangerous
universal donors were avoided. These donors, who are extremely
uncommon, have plasma that contains a high titer of anti-A
antibodies, which can produce an unmistakable hemolytic transfusion
reaction, with all the signs associated with major incompatibility.
Some of the recipient's own red blood cells might be eliminated by
antibodies in plasma from these donors, though there is no clinical
evidence of this phenomenon.
Casualties who received multiple transfusions over long periods
of time tended to develop greater sensitivity to pyrogens. This
observation, first recorded in 1951 (79), was never
explained.9
These same casualties were also prone to develop hemosiderosis
because of the excess iron deposited after increased erythrocytic
destruction. It was suggested, with the fear of hemochromatosis in
mind, that if these patients developed resistant chronic anemias,
whole blood and red blood cells should be used as sparingly as the
circumstances justified.
Patients who received more than 15 pints of blood often showed a
tendency to ooze from cut surfaces. The condition regressed quickly,
without treatment.
A patient in shock, who had been given a transfusion in excess of
the normal capacity of his circulatory system, sometimes developed
polycythemia. In such cases, the excess blood was apparently carried
in the dilated vessels of the skeletal muscles, liver, and lungs.
So-called overtransfusion, which was sometimes employed in severe
shock, was surprisingly well tolerated.
9 In the light of present (1962)
knowledge, this statement about sensitivity to Pyrogens may be
erroneous. The patients under discussion become sensitized to
known or unknown blood factors, and the sensitization tends to
cause reactions characterized by chills and fever during or
after subsequent transfusions.
805
Hematologic response.-A battery of hematologic studies was
carried out on 37 of the casualties received at the 46th Army
Surgical Hospital, located several miles behind the infantry
division that it supported, between October 1952 and January 1953.
Between 2 and 42 transfusions were used in each case. The plasma
hemoglobin was determined in 300 of the units used. Particular
attention was paid to the results of storage of blood (high plasma
hemoglobin and potassium, low labile factor activity, nonviable
platelets and leukocytes). As already mentioned, changes in stored
blood were slight and innocuous.
The important observations made in this study were as follows:
1. At the time of resuscitation and shortly thereafter, there was
a remark able loss of circulating red blood cell mass in casualties
with wounds associated with considerable tissue destruction. The
loss was thought to be caused by hemolysis, though the exact
mechanism was not determined. The loss of red cells was sometimes
so rapid that a casualty with bilateral traumatic amputation of both
legs, even if hemostasis was adequate, might become severely anemic
if there was any hesitation in using massive, rapid transfusions.
Shock associated with wounds which involved less tissue destruction,
such as lacerations of the colon, did not destroy red cells in this
fashion. After moderate transfusions, these patients often became
polycythemic, and transfusions had to be carried out "rather
gingerly," because of the tendency for signs of congestion to
appear.
2. During the early period of recuperation from severe wounds,
casualties tended to become anemic, apparently as the result of
hemolytic processes plus a relative inhibition of red cell
formation.
3. A particularly striking observation was that in patients not
in group O, massive transfusions of O blood resulted in the virtual
replacement of the recipient's cells by cells of the O group. His
plasma sometimes contained antibodies against red cells of his own
hereditary blood group. Gradual hemolysis of native red cells by
transfused antibodies was observed, but the hemolytic process was
not evident clinically and did not appear to harm the patient. The
presence of foreign antibodies, however, sometimes made it
impossible to crossmatch the patient with blood of his hereditary
group, and it was believed that transfusions with the hereditary
type of blood might be dangerous. Severe reactions, in fact,
sometimes occurred when type-specific blood was given after large
transfusions of O blood. In the light of this new observation, it
was recommended that, after transfusions of universal donor blood
had been given, no change should be made to blood of another group
until at least 2 weeks had elapsed.
Immunohematologic response.-Another special study by Colonel
Crosby and his associates was an investigation of 25 casualties from
the standpoint of the immunohematologic results of large
transfusions of group O blood in recipients of other blood groups.
These patients were all received by ambulance or helicopter between
1 and 3 hours after wounding. Transfusions
806
of plasma or whole blood had often been begun at battalion aid
stations and they were continued during evacuation, and, as needed,
through resuscitation and operation. Some patients received as much
as 37 pints of blood within 12 hours. One or two received 20 pints
within an hour. Most of the blood transfused was used before the
15th day, and none was used after the 21st day, of shelf life. All
the blood was group O, all was Rh-positive, and all was used without
crossmatching. It was tested for the high titer isoagglutinins
active against group A and group B red blood cells.
The important observations made in this study were as follows:
1. After large transfusions of low titer group O blood into
patients of groups A, B, and AB, it was not possible to demonstrate
foreign isohemolysins or incomplete antibodies in the recipient
serum. Cold isoagglutinins were frequently evident immediately after
the transfusion, but they usually disappeared rapidly. In several
patients, the titer of foreign anti-A isoagglutinins was quite high,
and the antibody persisted in the circulation for several days. A
possible explanation was the relatively small amount of A substance
in the recipient's blood; when the transfused isoagglutinins were
found persistent, the patients usually proved to be weak secretors
of A substance in the saliva, or complete nonsecretors.
2. In most of these patients there was evidence of selective
destruction of recipient red blood cells after the transfusion of O
blood, probably as the result of activity of transfused
isoantibodies in the plasma of the transfused blood. The hemolytic
activity was observed in cases in which it was not possible to
demonstrate the presence of foreign isoantibodies. It was postulated
that forms of antibodies might exist that could not be demonstrated
by available methods and that manifested themselves only by causing
destruction of red blood cells.
3. Clinically, as already mentioned, the hemolytic, process
originating from such transfused isoantibodies, while it caused
destruction of native red cells, did not threaten the lives or
impede the recovery of these patients. No reactions, in fact, were
encountered or heard of in Korea that might have been ascribed to
so-called dangerous universal donors. In practice, the division of
group O blood into high and low titer, on the basis of dilution of
1:200 to 1:256, proved perfectly safe.
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809
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