title: Immune heparin-induced thrombocytopenia can occur in patients receiving clopidogrel and aspirin.
abstract: Platelet adenosine diphosphate (ADP) receptors may play a role in potentiating platelet activation induced by IgG from patients with immune heparin-induced thrombocytopenia (HIT), as shown by previous studies using the ADP receptor antagonists AR-C66096 and ticlopidine. Consistent with these observations, we found that platelet activation by HIT sera is also significantly reduced in patients receiving clopidogrel, an ADP receptor antagonist prodrug now in wide clinical use. Despite these in vitro and ex vivo findings, we observed two patients develop acute HIT while receiving both clopidogrel and aspirin: both patients' sera tested strongly positive in a heparin-dependent washed platelet activation assay (100% serotonin release) and PF4/heparin-enzyme-immunoassay (2.594 and 2.190 absorbance units). Both patients also developed HIT-associated clinical sequelae (acute systemic reaction postintravenous heparin bolus; thrombotic stroke) in association with their episode of HIT. We conclude that combined therapy with aspirin and clopidogrel does not necessarily protect against clinical HIT, at least in patients with HIT antibodies that have strong platelet-activating characteristics.
authors.affiliation: Institute of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Selleng
authors.forename: Sixten
authors.initials: S
authors.lastname: Selleng
authors.forename: Ricarda
authors.initials: R
authors.lastname: Raschke
authors.forename: Carsten O
authors.initials: CO
authors.lastname: Schmidt
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Rosenblood
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Warkentin
mesh_terms: D000244:Adenosine Diphosphate / Q000276:immunology; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000276:immunology; D000925:Anticoagulants / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D000077144:Clopidogrel; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D010978:Platelet Factor 4 / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D013988:Ticlopidine / Q000009:adverse effects* / Q000031:analogs & derivatives*
chemical_list: D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D010978:Platelet Factor 4; D000244:Adenosine Diphosphate; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin