The fractionation process leading to immune globulin resulted
in overall reduction in HCV RNA by a factor of 4.7 x 10(4). Although the
presence of HCV RNA in the final product does not necessarily imply the presence
of infectious virus, this work suggests that
the safety of immune globulins with respect to HCV
transmission is not due solely to the partitioning of HCV away from the
immunoglobulin fraction.
Information about ISG
Immune serums (immune globulin)
provide passive immunity to infectious disease. The protection will be of rapid
onset, but of short duration (1-3 months). Immune sera are obtained from pooled
human plasma of either general population donors or hyperimmunized donors. It
may be administered either by intravenous (IV) or intramuscular (IM) injection.
Immune Globulin (Human) (IG)
is a solution of immunoglobulin G (IgG) indicated for
prophylaxis of hepatitis A, prevention or modification of
measles (Rubeola), and for immunoglobulin deficiency. It is
administered intramuscularly.
Additional specific immune globulins
for intramuscular administration are obtained from donors whose plasma
contains selected high titer antibodies. Products are available for use
in the passive prophylaxis of varicella-zoster, tetanus, hepatitis B,
rabies, and other infections. Another product, Rho(D) Immune Globulin
(Human), is for the prevention of sensitization to the Rho(D) antigen
and hemolytic disease of the newborn. Some of the intramuscular
immunoglobulin products have been subjected to heat- or
solvent/detergent-treatment.
Rh0(D) immune globulin is a plasma-derived product
comprised of anti-D immune globulin Suppression of Rh isoimmunization
related to transfusion or pregnancy: Intramuscular RhIg has been
successfully used to prevent the development of Rho (D)
antibodies for years. INTRAVENOUS (HUMAN) Rho(D) IMMUNE GLOBULIN A new
preparation for the treatment of ITP and Rh isoimmunization
Katherine A. Anderegg, M.D., Fellow, The Institute For Transfusion
Medicine Darrell J. Triulzi, M.D., Medical Director, The Institute For
Transfusion Medicine
July 1995, when it was first demonstrated
that the "new" screened commercial intramuscular
immunoglobulin lacked anti-gpE1/E2 neutralizing antibodies, whereas
the "old" unscreened commercial intramuscular immunoglobulin
contained high titers of these antibodies.9,12
From August 1978 until March 1979, 14 batches of
anti-D immune globulin contaminated with hepatitis C virus (HCV) genotype 1b
(20,000-480,000 copies/dose) from a single erythrocyte donor had been
administered for prophylaxis of rhesus isoimmunization throughout East
Germany. All 2,867
Subcutaneous injections of a drug containing human immunoglobulins
1974 and early 1975, several cases of viral hepatitis were reported in Italy
among subjects who had received subcutaneous injections of a drug containing
human immunoglobulins that was prescribed for the treatment of allergies.
The possibility that immunoglobulins can be responsible for the transmission
of viral hepatitis raises a number of theoretical and practical problems
concerning control and use of these blood products.
4.2.6 Intravenous anti-D immunoglobulin
Anti-D immunoglobulin is prepared from
the plasma of donors with high concentrations of anti-rhesus D antibody.
Intravenous anti-D immunoglobulin was first reported to be involved in the
transmission of HCV in an outbreak of NANBH that occurred in East Germany
between 1978 and 1979 (Dittmann et al 1991). A similar outbreak was also
reported in Ireland where 12 women received anti-D immunoglobulin
manufactured in 1977 that contained HCV-RNA sequences (Stevens et al 1984;
Power et al 1994; Power et al 1995a). Both of these outbreaks were traced to
index cases who donated HCV-antibody-positive blood.
Another intravenous preparation implicated in the
transmission of HCV was an immunoglobulin product, Gammagard, used to treat
primary immunodeficiency disorders such as hypogammaglobulinaemia. In the
USA, 43 people with acute HCV infection were reported to the Centers for
Disease Control and Prevention (CDC) between 1993 and mid 1994 where the
only risk factor for HCV infection was receipt of the intravenous
immunoglobulin, Gammagard (Anonymous 1994). Gammagard was subsequently
removed worldwide in early 1994. Preliminary epidemiological investigations
in the USA have indicated that no other intravenous immunoglobulin products
or intramuscular immune globulin have been associated with HCV transmission
(Anonymous 1994).
The recent introduction of anti-viral treatments used
in the manufacture of immunoglobulin products has substantially reduced the
risk of transmission of HCV to recipients of these products.
- Intramuscular
immune globulin is available in broad-spectrum form, or disease-specific
hyperimmune serum.
- Immune serum globulin
intramuscular (IM) (IG, Gamma
Globulin,
ISG, Gamastan, Gammar) (HCPCS/CPT
codes J1460-J1560) is indicated for the following conditions:
- Hepatitis A exposure (ICD-9: V01.7).
- Measles (Rubeola) : for a susceptible
patient (has not been vaccinated and has not had measles and is at
high risk for complication) who has been exposed less than three
days prior to treatment (ICD-9 V04.2 ).
- Rubella: for a woman in early
pregnancy, who is exposed to the virus and does not have immunity.
(ICD-9 V22.2 and V01.4; or 647.50; or 647.53)
- Varicella: for passive immunization in
immunosuppressed patients when varicella zoster immunoglobulin is
not available (ICD-9: V05.4).
- Immunoglobulin deficiency: for
prevention of serious infection when circulating IgG levels are low.
Prophylactic therapy, especially against infections due to
encapsulated bacteria, is often effective in Bruton-type, sex-linked
congenital agammaglobulinemia, agammaglobulinemia associated with
thymoma and acquired agammaglobulinemia (ICD-9: 042, 279.00-279.06,
279.2, 279.3). Therapy may not prevent chronic infections of
external secretory tissues such as the respiratory or GI tracts.
- Specific hyperimmune serum globulin
includes several different disease-specific drugs.
- Hepatitis B serum (CPT 90371) is
indicated post-exposure for transient prevention of hepatitis B
infection. (ICD-9 V15.85)
- Rabies serum (CPT 90375, 90376) is
indicated post-exposure for transient prevention of rabies infection
when the patient has not been completely immunized with the
vaccination. (ICD-9 V01.5)
- Vaccinia serum (CPT 90393) is
indicated for transient prevention of or modification of aberrant
infections induced by vaccinia (smallpox) vaccine, the vaccinia
virus, such as eczema vaccinatum, some cases of progressive vaccinia,
and possibly ocular vaccinia. (ICD-9 V01.4)
- Varicella-zoster serum (CPT 90396) is
indicated for transient prevention of varicella-zoster infection in
exposed, susceptible individuals who have a greater risk of
complications from varicella (ICD-9 V01.7). Documentation in the
progress notes must indicate one of the following complicating
conditions to verify medical necessity: - a personal history of
leukemia or lymphoma - HIV infection - current immunosuppressive
therapy - a newborn with exposure to chickenpox (the documentation
must indicate why the newborn is at increased risk; e.g., if the
mother was exposed within 5 days of delivery).
- Tetanus serum (J1670) is indicated for
transient protection against tetanus post-exposure to tetanus (ICD-9
code V03.7). Documentation in the progress notes must identify the
following: - The wound is other than a clean minor wound, and the
date of the injury; - The active immunization with tetanus toxoid is
unknown or uncertain; or - The patient has received either
less than 2 prior doses of tetanus toxoid; or two prior doses
of tetanus toxoid, but there has been a delay of 24 hours or more
between the time of injury and the initiation of tetanus
prophylaxis.
- *Intravenous immune globulin (IGIV,
Gamimune N, Gammagard, Gammar-IV, Iveegam, Sandoglobulin, Venogloblin-I)
(CPT codes J1563, *J1564) provides immediate antibody levels. IVIG has
been used as a therapy of last resort for some of the conditions and is
indicated only if standard approaches have failed, become intolerable,
or are contraindicated. IVIG may be indicated for the following
conditions:
- Immunodeficiency Syndrome: to include congenital
agammaglobulinemia such as x-linked aglobulinemia, common variable
hypoglobulinemia, x-linked immunodeficiency with hyper IGM, combined
immunodeficiency, and AIDS (ICD-9: 042, 279.00-279.06, 279.2)
- Idiopathic thrombocytopenic purpura (ICD-9:
446.6, 287.3).
- Alloimmune thrombocytopenia, refractoriness to
platelet transfusions (ICD-9 287.4). Routine use is not indicated. IVIG
may have a role in patients with severe thrombocytopenia of documented
immune basis for whom other modalities are unsuccessful or
contraindicated. IVIG may be used in neonates with severe immune
thrombocytopenia if other interventions are unsuccessful or
contraindicated. Maternal antenatal infusion may be considered.
- Post-transfusion purpura (ICD-9 287.4). IVIG may
be considered as first-line therapy in severely affected patients.
- B-Cell Chronic Lymphocytic Leukemia (ICD-9:
204.10)
- Autoimmune hemolytic anemia (ICD-9: 283.0).
Routine use is not indicated. IVIG may have a role in patients with
warm-type AIHA that does not respond to corticosteroids.
- Immune-mediated neutropenia (ICD-9 288.0).
Routine use is not indicated. IVIG may have a role in severe illness
that does not respond to other modalities or when the latter are
contraindicated.
- Multiple Myeloma (ICD-9 203.00-203.80). Routine
use is not indicated. It may have a role in patients with stable
(plateau phase) disease and high risk of recurrent infections.
- Pediatric intractable epilepsy (ICD-9 345.11,
345.3, 345.61). Routine use is not indicated. IVIG may have a role in
certain syndromes as a last resort, especially in patients who may be
candidates for surgical resection.
- Guillian-Baré syndrome (ICD-9 357.0). IVIG is
recommended as an equivalent alternative to plasma exchange in children
and adults.
- Myasthenia gravis (MG) (ICD-9 358.0). Routine use
is not indicated. IVIG may be considered in patients with severe MG to
treat acute severe decompensation when other treatments have been
unsuccessful or are contraindicated.
- Polyneuropathy, chronic inflammatory
demyelinating (ICD-9 357.8). IVIG is recommended as an equivalent
alternative to plasma exchange in children and adults.
- Dermatomyositis (ICD-9 710.3). Routine use is not
indicated. IVIG may be used in patients with severe active illness for
whom other interventions have been unsuccessful or intolerable.
- Polymyositis (ICD-9 710.4). Routine use is not
indicated. IVIG may be used in patients with severe active illness for
whom other interventions have been unsuccessful or intolerable.
- Systemic lupus erythematosus (SLE) (ICD-9 710.0).
Routine use is not indicated. IVIG may be used in patients with severe
active SLE for whom other interventions have been unsuccessful or
intolerable.
- Kawasaki disease (ICD-9 446.1).
- Severe Vasculitic Syndromes, systemic
(polyartaritis nodosa) (ICD-9 446.0). Evidence does not suppport routine
use of IVIG. IVIG may be used in patients with severe active illness for
whom other interventions have been unsuccessful. or intolerable.
- Intravenous
immune globulin for the treatment of autoimmune mucocutaneous blistering
diseases is a National Coverage Decision (NCD). It is binding on all
Medicare carriers, intermediaries, peer review organizations, health
maintenance organizations, competitive medical plans, and health care
prepayment plans. Under 42 CFR 422.256(b), an NCD that expands coverage
is also binding on a Medicare+Choice Organization. In addition, an
administrative law judge may not review an NCD. (See §1869(f)(1)(A)(i)
of the Social Security Act.)
Intravenous immune globulin (IVIg) (J1563) is a
blood product prepared from the pooled
plasma of donors. It has been used to treat a variety of autoimmune
diseases, including mucocutaneous blistering diseases. It has fewer side
effects than steroids or immunosuppressive agents.
To make immune serum globulin ( ISG) products, plasma
is treated with a variety of substances to separate the desired proteins
from others, in a process called fractionation. Fractionation process
used today is the Cohn-Oncley method. This process relies on precipitation
of plasma proteins by a combination of cold alcohol (usually ethanol)-water
mixtures and adjustments of pH, ionic strength, temperature, and protein
concentration.
The fractionation process leading to immune globulin resulted
in overall reduction in HCV RNA by a factor of 4.7 x 10(4). Although the
presence of HCV RNA in the final product does not necessarily imply the presence
of infectious virus, this work suggests that
the safety of immune globulins with respect to HCV
transmission is not due solely to the partitioning of HCV away from the
immunoglobulin fraction.
Alternatively, some manufacturers separate plasma
derivatives by column chromatography using ion exchange, gel filtration, or
affinity methods, without alcohol. In all cases, fractions of plasma are
separated sequentially, with the product from one step, such as the
precipitate and/or supernatant, becoming the starting material for the next
step in the fractionation process. If each step is not done properly,
subsequent fractions can be adversely affected. Thus, the integrity of each
final product is dependent on all of the preceding steps in the process.
After
fractionation, derivatives undergo further processing to purify and
concentrate proteins and to inactivate or remove (clearance) any
bacterial or viral contaminants. While early steps in the manufacturing
process are not performed aseptically, all final products must be
sterile. Types of viral clearance include those steps that are
part of the fractionation process itself, e.g., pH4/pepsin or
polyethylene glycol (PEG) fractionation, or those steps that are
deliberately added, e.g., solvent/detergent treatment or viral
filtration. In some instances more than one viral clearance step is used
for a given product. Plasma derivatives are similar to other biological
products in that they are protein-based and subject to denaturization at
high temperatures. These products are usually filled by using aseptic
processing techniques, and cannot be terminally sterilized, although in
some instances they can be heat-treated in the final container to effect
viral or bacterial inactivation.
