In Vitro Efficacy of Platelet Glycoprotein IIb/IIIa Antagonist in Blocking Platelet Function in Plasma of Patients with Heparin-induced Thrombocytopenia

Koon-Hou Mak; Kandice Kottke-Marchant; Linda M. Brooks; Eric J. Topol

doi:10.1055/s-0037-1615399

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1998; 80(06): 989-993
DOI: 10.1055/s-0037-1615399

Letters to the Editor

Schattauer GmbH

In Vitro Efficacy of Platelet Glycoprotein IIb/IIIa Antagonist in Blocking Platelet Function in Plasma of Patients with Heparin-induced Thrombocytopenia

Authors

Koon-Hou Mak

¹Department of Cardiology and Joseph J. Jacobs Center for Vascular Biology
Kandice Kottke-Marchant

²Dept. of Clinical Pathology, The Cleveland Clinic Foundation, Cleveland, OH, USA
Linda M. Brooks

²Dept. of Clinical Pathology, The Cleveland Clinic Foundation, Cleveland, OH, USA
Eric J. Topol

¹Department of Cardiology and Joseph J. Jacobs Center for Vascular Biology

Abstract

Summary

Heparin-induced thrombocytopenia (HIT) is an important complication following administration of heparin. Platelet activation and aggregation induced by heparin/platelet factor 4/immunoglobulin complexes are thought to be the underlying mechanism for this condition, so it was hypothesized that abciximab (a humanized murine monoclonal antibody directed against the glycoprotein IIb/IIIa receptor) would prevent heparin-induced platelet aggregation and activation in plasma from patients with HIT. Platelet aggregation was tested in vitro with platelet-poor plasma (obtained from 23 patients with HIT), platelet-rich plasma (from normal donors with known reactivity), heparin (0.5 U/ml), and ascending doses of abciximab (0.07-0.56 μg/ml). The ability of abciximab to prevent platelet activation was also evaluated using flow cytometry (P selectin expression, mepacrine release, microparticle formation) and platelet factor 4 immunoassay. In vitro, abciximab inhibited heparin-induced platelet aggregation in a dose-dependent fashion (IC₅₀ 0.103 μg/ml) and inhibited microparticle formation, the expression of P-selectin, release of mepacrine and platelet factor 4. These findings suggest that abciximab may be useful in treatment of patients with HIT and warrants further clinical evaluation.

Full Text

References

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