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(Circulation. 2001;103:643.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Prognostic Significance of Thrombocytopenia During Hirudin and Heparin Therapy in Acute Coronary Syndrome Without ST Elevation

Organization to Assess Strategies for Ischemic Syndromes (OASIS-2) Study

John W. Eikelboom, MBBS, MSc, FRACP, RCPA; Sonia S. Anand, MD, MSc, FRCPC; Shamir R. Mehta, MD, FRCPC; Jeffrey I. Weitz, MD, FRCPC; Cheelong Yi, BSc, MSc, PhD; Salim Yusuf, MBBS, DPhil, FRCPC, FRCP(UK)

From the Preventive Cardiology and Therapeutics Program (J.W.E., S.S.A., S.R.M., C.Y., S.Y.), Department of Medicine (S.S.A., S.R.M., J.I.W., S.Y.), and Hamilton Civic Hospital Research Centre (J.I.W.), McMaster University, Hamilton, Canada.

Background—The development of thrombocytopenia in acute coronary syndromes (ACS) appears to be associated with adverse clinical outcomes. Unfractionated heparin is a recognized cause of thrombocytopenia, but the incidence, predictors, and prognostic significance of thrombocytopenia during hirudin therapy in ACS have not been reported.

Methods and Results—Patients with ACS without ST elevation were randomized in a double-blind manner to receive a 72-hour intravenous infusion of unfractionated heparin or hirudin. Platelet counts were measured at baseline and within 24 hours of completion of study drug. The overall incidence of thrombocytopenia (<100x10⁹/L) was 1% and was similar in unfractionated heparin– and hirudin-treated patients (P=0.42). Thrombocytopenia during study drug infusion was an independent predictor of 7-day outcomes, including death (OR, 6.7; 95% CI, 1.9 to 25); the composite of death, myocardial infarction, and recurrent ischemia (OR, 2.0; 95% CI, 1.0 to 1.5); revascularization (OR, 4.0; 95% CI, 2.2 to 7.1); and major bleeding (OR, 8.3; 95% CI, 3.4 to 17.7). Among patients who developed thrombocytopenia, hirudin (OR, 5.4; 95% CI, 2.6 to 11.3) but not unfractionated heparin (OR, 2.0; 95% CI, 0.3 to 14.4) therapy was associated with a significantly increased risk of major bleeding.

Conclusions—Early-onset thrombocytopenia in patients with ACS without ST elevation is strongly associated with adverse clinical outcomes, including death, ischemic events, and bleeding. The excess of major bleeding in hirudin-treated patients who develop thrombocytopenia suggests that thrombocytopenia may contribute to the increased risk of bleeding observed with hirudin.

Key Words: platelets • heparin • hirudin • angina • myocardial infarction

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