Читать книгу Transfusion Medicine - Jeffrey McCullough - Страница 151

Immune serum globulin (Ig or gamma globulin) prepared by the traditional plasma fractionation technique has been very effective in preventing bacterial infections in patients with agammaglobulinemia and in preventing certain viral infections in immunologically normal persons. Immune globulin is administered intramuscularly because it contains aggregated or oligomeric molecules of Ig, which, when injected intravenously, activate complement, resulting in severe reactions [112]. The limitations of intramuscular Ig are dose, painful injections because of the volume required, and difficulty maintaining plasma levels of IgG. To overcome these issues, immune globulin suitable for intravenous administration is prepared from the plasma of normal donors and thus can be expected to have an antibody content reflective of normal healthy individuals in a large population. There are some differences among different products in the IgA content, the relative proportions of IgG subclasses, and in vitro activity against some viruses. The differences in IgA content are clinically important, because brands that contain much IgA may cause a reaction if given to an IgA‐deficient patient with anti‐IgA. The importance of the other differences among the brands has not been established. The intravenous half‐life of the intravenous immunoglobulin (IVIG) is 21–25 days, which is similar to native IgG.

All IVIG products that are approved by the FDA are labeled for treatment of individuals with impaired humoral immunity, specifically for primary (congenital) immune deficiency. Individual products are additionally labeled for use in (idiopathic) autoimmune thrombocytopenia, chronic inflammatory demyelinating polyneuropathy, Kawasaki syndrome, HIV infection during childhood, bone marrow transplant, and B‐cell chronic lymphocytic leukemia [113–115]. The availability of IVIG makes it possible to maintain the serum IgG level near normal in immunodeficient patients. The amount required varies with the size of the patient and the indication. Usually 100–200 mg/kg per month is used as a starting dosage for patients with primary immunodeficiencies.

Administration of IVIG in autoimmune situations may seem odd. The mechanism of action is thought to be macrophage Fc receptor blockage by immune complexes formed between the IVIG and native antibodies. IVIG is effective for patients with autoimmune thrombocytopenia. Specific IV anti‐Rh(D) is used in Rh‐positive patients with autoimmune thrombocytopenia [113, 116]. This is thought to cause immune complexes with anti‐Rh and the patient’s Rh‐positive red cells, resulting in Fc receptor blockade. Larger doses are usually used for patients with autoimmune thrombocytopenic purpura compared with immune deficiency. IVIG is now used in other immune deficiency or autoimmune states (see Chapter 10).

Adverse reactions to IVIG occur with 2–10% of injections [113]. These are local, such as erythema, pain, phlebitis, or eczema. Systemic symptoms include fever, chills, myalgias, back pain, nausea, and vomiting. Some reactions in some patients are dose related and can be reduced or eliminated by slowing the rate of infusion. The nature and frequency of adverse reactions may differ among the different products, but this is not clear and is beyond the scope of this chapter.

Because IVIG is made from large pools of human plasma, it contains a variety of antibodies, including those against blood groups and possibly anti‐HBs, anti‐HBc, anti‐cytomegalovirus, and so on [113]. Donor screening should eliminate some of these (i.e., anti‐HIV), but patients may have transiently positive tests for certain antibodies, especially ABO, that are passively acquired from the IVIG [117], and some patients may develop a positive direct antiglobulin test. Transient hemolysis has been reported in patients with autoimmune thrombocytopenic purpura and others being treated with IVIG (see Chapter 16). Thus, although hemolysis is unusual, a large proportion of patients receiving IVIG will develop circulating or cell‐bound blood group antibodies. This should be considered if unexplained hemolysis occurs in patients being treated with IVIG.