Blood dyscrasias secondary to non-steroidal anti-inflammatory drugs.
Drug reactions may be classified into 2 categories. The first category comprises reactions to the pharmacological properties of the drug which is given either in excessive amounts or to a subject who is highly susceptible to a given pharmacological action (e.g. G6PD-deficient subjects with regard to oxidants and patients with von Willebrand's disease with regard to drugs which inhibit platelet aggregability). The second category concerns reactions caused by a drug-dependent immune mechanism. By far the largest proportion of NSAID-induced side effects belong to the second category. The sensitising potential of a drug is probably connected to its protein-binding capacity. The clinical aspect depends on the type of immune reaction as well as its localisation within the organism. Cellular immunity usually leads to erythematous skin rashes. However, it is possible that some of the haematological side effects may be caused by T-lymphocytes reacting specifically with haematopoietic cells to which a drug adheres. Antibody-mediated immune reactions are more common. Today, we can distinguish 5 different mechanisms: IgE-mediated drug reactions usually lead to eosinophilia, sometimes with eosinophilic infiltrates in the lung. In such cases, patients frequently develop urticarial rashes. In a number of drug-induced cytopenias the underlying mechanism resides in the action of soluble immune complexes on red cells, leucocytes or platelets as in the case of agranulocytosis secondary to medication with pyrazoles. IgG and/or IgM may be implicated in the formation of the immune complexes. In this system, blood cells are affected when incubated with the serum of an allergic subject previously incubated with the offending drug or one of its metabolites. Some drugs or drug metabolites have a strong affinity for certain blood cells to which they become attached. If a patient develops antibodies to these drugs, an antibody interaction with the drug-coated cells can lead to the destruction of the cells. This mechanism may be operative not only in the periphery but also within the bone marrow. In the serological testing, preincubation of the serum with the offending drug will inhibit the reaction of the antibody to drug-coated cells. This mechanism may coexist with the immune complex type of blood cell damage. Today it appears established that patients may develop antibodies the specificity of which depends on a drug as well as on a membrane component of blood cells. The haematological specificity of the immune reaction would then be explained by the autoantigenic constituent of the drug-autoantigen complex.(ABSTRACT TRUNCATED AT 400 WORDS)
D000380:Agranulocytosis / Q000139:chemically induced; D000740:Anemia / Q000139:chemically induced*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis; D004342:Drug Hypersensitivity / Q000209:etiology; D006384:Hemagglutination; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D006454:Hemoglobins