Immune complex-mediated reaction

The bleeding potential is similar among the agents. However, thrombocytopenia, particularly profound thrombocytopenia (platelet count <50,000 mrrT3) occurs with a two-to four-fold higher frequency with abciximab (0.4— 1.0%) compared with eptifibatide (0-0.2%) or tirofiban (0,1 —0.3%) (6), The exact mechanism of this difference is not clear, However, immune complex-mediated reaction (due to an anamnestic response to the humanized chimeric antibody) may contribute to rapid precipitation of thrombocytopenia with abciximab (6), Platelet counts should, therefore, be measured early (within the first one to four hours) after administration of these agents and followed for the duration of therapy. Platelet transfusion should be considered for profound thrombocytopenia with or without serious bleeding (6). 

Innnunologic Dextran 70 has been used as stabilizer in a measles-mumps-rubella (MMR) vaccine product named Morupar. This vaccine was associated with dextran-driven hypersensitivity reactions with high concentrations of dextran-spedfic IgG [43"]. The most probable mechanism is immune complex-mediated reactions caused by naturally occurring dextran-specific antibodies. Morupar was withdrawn from the market. 

Edwards and Jones (31) identified the condensed tannin extracted from cotton plant bracts as a tannin-like polymer of 5, 7, 3, 4 tetrahydroxyflaven 3-4 diol (THF). They demonstrated nonspecific precipitation with IgG, IgM, IgA, five myeloma IgG s and positive gel diffusion reactions with heavy and light chains. Fab and Fc pieces of IgG. Nevertheless, they refuted this reaction as a true antigen-antibody reaction, and subsequently suggested that byssinosis was not an immune complex mediated pulmonary disease. 

Immediate hypersensitivity Hay fever, urticaria, atopic asthma Antibody-dependent cytotoxic hypersensitivity Immune complex mediated hypersensitivity (Arthus reaction)... 

Penicillins can cause all four types of hypersensitivity responses provoking type I IgE-mediated reactions such as urticaria, angioedema, asthma, and anaphylaxis type n antibody-mediated hemolytic anemia and thrombocytopenia type III immune complex-mediated serum sickness-like reactions and vasculitis and type IV T cell-mediated contact dermatitis, rashes, and other skin eruptions (refer to Chaps. 2 and 3). Table 5.1 lists clinical adverse reactions, together with their immune... 

Table 13.1). Other more severe symptoms sometimes reported are bronchospasm, chest pain, seizures, and systemic anaphylaxis that may be life-threatening. Reactions to oxaliplatin are similar to those seen in response to cisplatin and carboplatin, but the responses to oxali-plafin tend to be more heterogeneous and unpredictable with fewer cutaneous reactions idiosyncratic reactions like cytokine release syndrome and pulmonary fibrosis fewer reports of severe anaphylaxis and a higher incidence of respiratory symptoms including laryngeal spasms and hypoxemia A few cases of type II thrombocytopenia and type HI immune complex-mediated urticaria, joint pain, and proteinuria associated with oxaliplatin have also been reported. 

Mechanisms underlying non-IgE mediated food allergy include immune complex formation and activation of lymphocytes. As with IgE-mediated responses, manifestations can be in the skin, gut, or respiratory tract however, these reactions take several hours to days to develop [65],... 

Types II and III Hypersensitivity. No simple animal models are currently available to assess Type II (antibody-mediated cytotoxicity) hypersensitivity reactions. IgE antibodies and immune complexes in the sera of exposed animals can be assayed using ELISA or RIA techniques that require the use of specific antibodies to the drug. 

Most anaphylactoid reactions are due to a direct or chemical release of histamine, and other mediators, from mast cells and basophils. Immune-mediated hypersensitivity reactions have been classified as types I-IV. Type I, involving IgE or IgG antibodies, is the main mechanism involved in most anaphylactic or immediate hypersensitivity reactions to anaesthetic drugs. Type II, also known as antibody-dependent hypersensitivity or cytotoxic reactions are, for example, responsible for ABO-incompatible blood transfusion reactions. Type III, immune complex reactions, include classic serum sickness. Type IV, cellular responses mediated by sensitised lymphocytes, may account for as much as 80% of allergic reactions to local anaesthetic. 

Figure 6.33 The basis of type III hypersensitivity reactions. These are mediated by immune complexes formed between antigen and IgG antibodies, which accumulate in capillaries and in tissues.

The newer derivatives seem less likely to cause hypersensitivity reactions, perhaps because the protein adducts generated are shorter lived. All four types of hypersensitivity reaction have been observed with penicillin. Thus, high doses may cause hemolytic anemia and immune complex disease and cell-mediated immunity may give rise to skin rashes and eruptions, and the most common reactions are urticaria, skin eruptions, and arthralgia. Antipenicillin IgE antibodies have been detected consistently with an anaphylactic reaction. The anaphylactic reactions (type 1 see above), which occur in 0.004% to 0.015% of patients, may be life threatening. 

Non-IgE-antibody-mediated immunological reactions Modification of erythrocyte surface components due to binding of beta-lactams or their metabolic products is thought to be the cause of the formation of antierythrocyte antibodies and the development of a positive Coombs test implicated in the development of immune hemolytic anemia (211). About 3% of patients receiving large doses of intravenous penicillin (10-20 million units/ day) will develop a positive direct Coombs test (212). However, only a small fraction of Coombs positive patients will develop frank hemolytic anemia (213). Antibody-coated erythrocytes are probably eliminated by the reticuloendothelial system (extravascular hemolysis) (214), or less often by complement-mediated intravascular erythrocyte destruction (215). Another mechanism implicates circulating immune complexes (anti-beta-lactam antibody/beta-lactam complexes), resulting in erythrocyte elimination by an innocent bystander mechanism (82). Similar mechanisms have been implicated in thrombocytopenia associated with beta-lactam antibiotics (216,217). 

The authors suggested that dextran-reactive antibodies had formed immune complexes with dextran, leading to complement activation and release of mediators of anaphylaxis. There was also evidence of mast cell degranulation. They therefore recommended that titration of dextran-reactive antibodies before administration of dextrans could provide a method of identifying those who are at risk of dextran-induced anaphylactic reactions. 

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