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Drug-induced thrombocytopenia and thrombosis: Evidence from patients receiving an oral glycoprotein IIb/IIIa inhibitor in the Orbofiban in Patients with Unstable coronary Syndromes- (OPUS-TIMI 16) trial

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Abstract

Objective: To assess etiology and impact of thrombocytopenia in a large oral glycoprotein (GP) IIb/IIIa inhibitor trial.

Background: Heparin is known to cause thrombocytopenia, and in some of these patients thrombosis. GP IIb/IIIa inhibitors are also associated with thrombocytopenia.

Methods: The Orbofiban in Patients with Unstable Coronary Syndromes (OPUS-TIMI 16) Trial randomized 10,392 patients with ACS to the oral GP IIb/IIIa inhibitor orbofiban or placebo. Patients were followed for a minimum of ten months. Thrombocytopenia was defined prospectively as a platelet count < 80,000.

Results: Thrombocytopenia was rare in the OPUS-TIMI 16 trial (0.68% at Day 30 and 0.80% at 1 year), but more common in patients treated with orbofiban (0.92%) compared with those treated with placebo (0.2%), p < 0.001. Patients who developed thrombocytopenia had higher rates of death (11.6% vs. 1.7%, p < 0.001), recurrent MI (12.1% vs. 2.8%, p < 0.001), intracranial hemorrhage (2.9% vs. 0.0%, p < 0.001), and major or severe bleeding (19.0% vs. 2.0%, p < 0.001) at 30 days (with similar results at one year).

Conclusion: Thrombocytopenia, though uncommon, was associated with orbofiban use and an increased risk of bleeding, but also death and MI. This study provides further evidence that drugs that lead to thrombocytopenia are, in a significant proportion of patients associated with thrombotic events.

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Authors and Affiliations

  1. TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis st., Boston, MA, 02115

    Benjamin M. Scirica, Christopher P. Cannon, Carolyn H. McCabe & Eugene Braunwald

  2. Health Policy Institute, Medical College of Wisconsin, Wisconsin

    Richard Cooper

  3. Blood Research Institute, The Blood Center of Southeast Wisconsin, Wisconsin

    Richard H. Aster

  4. Pharmacia, Skokie, IL

    Jacqueline Brassard

  5. Nottingham Clinical Research Group, Nottingham, England

    Andrew Charlesworth & Allan M. Skene

Authors
  1. Benjamin M. Scirica
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  2. Christopher P. Cannon
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  3. Richard Cooper
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  4. Richard H. Aster
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  5. Jacqueline Brassard
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  6. Carolyn H. McCabe
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  7. Andrew Charlesworth
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  8. Allan M. Skene
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  9. Eugene Braunwald
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Correspondence to Benjamin M. Scirica.

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Scirica, B.M., Cannon, C.P., Cooper, R. et al. Drug-induced thrombocytopenia and thrombosis: Evidence from patients receiving an oral glycoprotein IIb/IIIa inhibitor in the Orbofiban in Patients with Unstable coronary Syndromes- (OPUS-TIMI 16) trial. J Thromb Thrombolysis 22, 95–102 (2006). https://doi.org/10.1007/s11239-006-8669-4

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  • DOI: https://doi.org/10.1007/s11239-006-8669-4

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