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.