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Acute thrombocytopenia in patients treated with amiodarone is caused by antibodies specific for platelet membrane glycoproteins
Author(s) -
Sahud Mervyn A.,
Caulfield Michael,
Clarke Nigel,
Koch Robert,
Bougie Daniel,
Aster Richard
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12521
Subject(s) - amiodarone , antibody , platelet , glycoprotein , chemistry , platelet membrane glycoprotein , medicine , immunology , pharmacology , biochemistry , atrial fibrillation
Summary 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 I g G antibodies in patient serum to platelets. Solid phase assays identified drug‐dependent antibodies specific for platelet glycoproteins ( GP )Ia/ II a (integrin α 2 β 1 ) in each patient and a second antibody specific for GPII b/ III a (α II b β 3 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 GPI a/ II a and/or GPII b/ III a. 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.