Glycoprotein IIb/IIIa antagonists: potential induction and detection of drug-dependent antiplatelet antibodies.
Development of acute, severe thrombocytopenia has been reported in several patients treated with a chimeric monoclonal antibody fragment to the platelet glycoprotein IIb/IIIa (GPIIb/IIIa) complex. However, the propensity of oral GPIIb/IIIa antagonists to induce antibody-mediated thrombocytopenia or platelet dysfunction with chronic exposure is unknown. There is evidence to suggest that a small percentage of otherwise healthy individuals have preexisting serum antibodies to conformation-dependent epitopes in the GPIIb/IIIa complex that are induced by certain members of this class of compounds that function as mixed agonists/antagonists. Additional studies are needed to identify the epitopes recognized by these antibodies and the requirement for the drug or a drug-metabolite to be present for antibody binding and detection. Detailed immunologic studies of antibodies from patients in whom immune thrombocytopenia develops after receiving oral GPIIb/IIIa antagonists may also provide insight into the mechanism by which activated platelets are normally cleared from the circulation.
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The Department of Pathology and Laboratory Medicine of the University of Pennsylvania, Philadelphia, USA.
D000818:Animals; D000906:Antibodies / Q000032:analysis* / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D000917:Antibody Formation / Q000187:drug effects; D000918:Antibody Specificity / Q000502:physiology; D001792:Blood Platelets / Q000276:immunology*; D006801:Humans; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013921:Thrombocytopenia / Q000139:chemically induced
D000906:Antibodies; D000911:Antibodies, Monoclonal; D019039:Platelet Glycoprotein GPIIb-IIIa Complex