Antibody-dependent drug

In contrast to a-methyldopa-induced hemolytic anemia, most drug-induced hemolytic anemia, especially for penicillins [34] and cephalosporins [35], involves drug-dependent antibodies, presumably because the drug acts as a hapten to directly modify erythrocytes or form immune complexes [36], However, there are many examples where a drug, such as nomifensine, induces both drug- (or metabolite)-dependent and drug-... 

Many drugs, especially quinidine and heparin, induce antibodies leading to thrombocytopenia. In most cases the antibodies are drug-dependent however, there are many examples in which the antibodies are autoimmune in nature [42], even for drugs, such as quinidine that are classically associated with drug-dependent antibodies [43], Gold therapy, in particular, is associated with autoimmune-thrombocytopenia [44],... 

Salama, A. et al., Diclofenac-induced immune haemolytic anaemia Simultaneous occurrence of red blood cell autoantibodies and drug-dependent antibodies, Br. J. Haematol., 95, 640, 1996. 

Lemer, W. et al, Drug-dependent and non-drug-dependent antiplatelet antibody in drug-induced immunologic thrombocytopenic purpura, Blood, 66, 306, 1985. 

Immune hemolytic anemia has been reported in a 67-year-old man taking mercaptopurine for chronic myelomonocytic leukemia (17). Serology showed a positive direct antiglobuhn test and confirmed the presence of mercaptopurine drug-dependent antibodies. He improved and the direct antiglobulin test was no longer positive 20 days after mercaptopurine withdrawal. 

Chambers LA, Donovan LM, Kruskall MS. Ceftazidime-induced hemolysis iu a patient with drug-dependent antibodies reactive by immune complex and drug adsorptiou mechanisms. Am J Chn Pathol 1991 95(3) 393-6. 

Thrombocytopenia has rarely been reported, always associated with cefalotin (83-85). In one case there were drug-dependent antibodies. In two other cases the role of drug-dependent antibodies was further evaluated. In one case the antibodies only reacted with platelets in the presence of exogenons cefotetan, but not with cefotetan-coated platelets (86). In another case associated with cefamandole, antibodies cross-reacted with two cephalosporins that had a thiomethyltetrazole gronp at position 3 but not with other cephalosporins (87). In an additional case, cefuroxime has been implicated (88). In abont one-third of cases with cephalosporin-indnced nentropenia, slight concomitant thrombocjdopenia has been found (73). 

Thrombocytopenia with penicillins has very rarely been reported (57-61). In two cases with mezlocillin (62) and piperacillin + azobactam (63) antibodies became attached to the platelets in the presence of the incriminated drug. The second of these cases is of particular interest, since drug-dependent antibodies were found in the presence of piperacillin but not tazobactam. 

Immune thrombocytopenia during rifampicin therapy has been attributed to drug-dependent binding of an IgG antibody to platelets the binding epitope of the antibody was found in the glycoprotein Ib/IX complex (38). 

Cines DB. Glycoprotein Ilb/IIIa antagonists Potential induction and detection of drug-dependent antiplatelet antibodies. Am Heart J 1998 135 S152-S159. 

The drug most commonly used in clinical practice that can produce immune thrombocytopenic purpura is heparin. Other examples are sulfonamides, thiazide diuretics, chlorpropamide, quinidine, and gold. These types of immune thrombocytopenic purpura are reversed when the drug is withdrawn. Molecular mechanisms for the formation of specific drug-dependent antibodies appear to be very similar. The glycoproteins on the platelet surface interact with the drugs to form neo-epitopes. Subsequent... 

Drug-dependent antibodies causing IMHA have been found in AIDS patients (Gonzalez et al, 2003). Other cases of IMHA after the administration of tei-coplanin, a glycopeptide antibiotic (Coluccio et al., 2004) and by a metabolite of etodolac, a nonsteroidal anti-inflammatory drug (Cunha et al., 2000), have also been reported. Hemolytic anemia associated with antibodies to older drugs like tolbutamide and phenacetin have been known for decades (Bird et al.,1972). 

Gonzalez CA, Guzman L, Nocetti G Drug-dependent antibodies with immune hemolytic anemia in AIDS patients. Immunohematology 2003 19(1) 10-15. 

In the absence of a convenient and sensitive way to document that a particular drug is actually the cause of neutropenia, a high index of suspicion is particularly important. Drug-dependent antibodies can sometimes be identified using methods comparable to those described above for platelet-dependent antibodies. Whether the paucity of... 

Christie DJ, Mullen PC, Aster RH (1985) Fab-mediated binding of drug-dependent antibodies to platelets in quinidine- and quinine-induced thrombocytopenia. J Clin Invest 75 310-314 Cunha PD, Lord RS, Johnson ST, Wilker PR, Aster RH, Bougie DW (2000) Immune hemolytic anemia caused by sensitivity to a metabolite of etodolac, a nonsteroidal anti-inflammatory drag. Transfusion 40 663-668... 

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