title: Acute thrombocytopenia in patients treated with amiodarone is caused by antibodies specific for platelet membrane glycoproteins.
abstract: Amiodarone has been implicated as a cause of thrombocytopenia but the responsible mechanism is unknown. We performed studies in three patients to characterize the pathogenesis of this complication. No amiodarone-dependent, platelet-reactive antibodies were identified using conventional serological techniques. However, water-insoluble amiodarone solubilized in methanol and diluted to 1·0 mg/ml in aqueous buffer reproducibly promoted binding of IgG antibodies in patient serum to platelets. Solid phase assays identified drug-dependent antibodies specific for platelet glycoproteins (GP)Ia/IIa (integrin α2 β1 ) in each patient and a second antibody specific for GPIIb/IIIa (αII b β3 integrin) in one patient. When studied by ion mobility analysis and transmission electron microscopy, the serologically active amiodarone preparation, a milky suspension, was found to consist of particles 2-30 nm in diameter, typical of a coacervate, a state characteristic of amiodarone in aqueous medium. The findings provide evidence that thrombocytopenia in the three patients studied was caused by drug-dependent antibodies specific for platelet glycoproteins GPIa/IIa and/or GPIIb/IIIa. We postulate that, in vivo, amiodarone may become incorporated into occult lipophilic domains in platelet glycoproteins, producing structural modifications that are immunogenic in some individuals, and that the resulting antibodies can cause platelet destruction in a person taking this drug.
authors: Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA.
authors: Mervyn A
authors: MA
authors: Sahud
authors: Michael
authors: M
authors: Caulfield
authors: Nigel
authors: N
authors: Clarke
authors: Robert
authors: R
authors: Koch
authors: Daniel
authors: D
authors: Bougie
authors: Richard
authors: R
authors: Aster
mesh_terms: D000208:Acute Disease; D000368:Aged; D000638:Amiodarone / Q000009:adverse effects*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins / Q000276:immunology*; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology*
chemical_list: D000889:Anti-Arrhythmia Agents; D001323:Autoantibodies; D007074:Immunoglobulin G; D010980:Platelet Membrane Glycoproteins; D000638:Amiodarone
keywords: amiodarone (Cordarone®); drug-induced thrombocytopenia; immune thrombocytopenia
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