Drug-Antibody-Platelet Interaction in Quinine- and Quinidine-induced Thrombocytopenia

AUTOR(ES)

Christie, Douglas J.

RESUMO

Binding of quinine- and quinidine-dependent antibodies to platelets was studied using an electroimmunoassay to measure platelet-bound IgG. Antibodies from four patients with drug-induced thrombocytopenia differed significantly in their interaction with platelets: association constants for binding to platelets at high drug concentrations ranged from 0.29 to 2.6 × 107 M−1, the maximum number of antibody molecules bound ranged from 36,000 to 161,000/platelet, the amount of drug necessary to achieve half-maximum binding of antibodies to platelets ranged from 2 to 60 μM, and only one of the antibodies cross-reacted with the stereoisomer of the drug to which the patient was sensitized. Binding of the antibodies to platelets was enhanced at the highest achievable molar ratio of drug:antibody, 10,000:1, rather than being inhibited, as would be expected in a conventional, hapten-dependent reaction. The drug-antibody-platelet reaction was unaffected by Factor VIII/von Willebrand protein, nonspecifically aggregated IgG, or heat-labile complement components. After pretreatment with tritiated quinine, platelets retained several hundred thousand molecules of drug each, but failed to bind detectable amounts of antibody. However, platelets treated simultaneously with quinine-dependent antibody and tritiated quinine retained significantly more drug after repeated washes than platelets treated with drug and normal serum.

Documentos Relacionados

• Study of the factors that cause specific transformation in cultures of lymphocytes from patients with quinine- and quinidine-induced immune thrombocytopenia.
• Fatal Quinidine-Induced Thrombocytopenia following Open-Heart Surgery
• Quinine- and Quinidine-dependent Antiplatelet Antibodies: REQUIREMENT OF FACTOR VIII-RELATED ANTIGEN FOR PLATELET DAMAGE AND FOR IN VITRO TRANSFORMATION OF LYMPHOCYTES FROM PATIENTS WITH DRUG-INDUCED THROMBOCYTOPENIA
• Fab-mediated binding of drug-dependent antibodies to platelets in quinidine- and quinine-induced thrombocytopenia.
• Direct quantification of apparent binding indices from quinidine-induced in vivo conduction delay in canine myocardium.