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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:323.)
© 2002 American Heart Association, Inc.

Thrombosis

Inhibition of Platelet Glycoprotein Ib, Glycoprotein IIb/IIIa, or Both by Monoclonal Antibodies Prevents Arterial Thrombosis in Baboons

Dongmei Wu; Muriel Meiring; Harry F. Kotze; Hans Deckmyn; Nancy Cauwenberghs

From the Laboratory for Thrombosis Research (D.W., H.D., N.C.), Interdisciplinary Research Center, KU Leuven Campus Kortrijk, Kortrijk, Belgium, and the Department of Haematology and Cell Biology (M.M., H.F.K.), University of the Orange Free State, Bloemfontein, South Africa.

Correspondence to Prof Dr Hans Deckmyn, Laboratory for Thrombosis Research-IRC, K U Leuven Campus Kortrijk, E. Sabbelaan 53, B-8500 Kortrijk, Belgium. E-mail Hans.Deckmyn{at}kulak.ac.be

The antithrombotic efficacy of the monoclonal antibodies 6B4-Fab and MA-16N7C2 against platelet glycoprotein (GP) Ib and GP IIb/IIIa, respectively, on acute platelet-mediated thrombosis was evaluated in a baboon model of femoral artery stenosis, which is a modification of the original Folts model: platelet thrombi form on the injured stenosed artery, producing cyclic flow reductions (CFRs). A dose of 0.6 mg/kg 6B4-Fab significantly reduced the CFRs by 59±15%, whereas 2 mg/kg 6B4-Fab completely abolished the CFRs without prolongation of the bleeding time. MA-16N7C2 inhibited CFRs by 43±8% at a dose of 0.1 mg/kg and abolished the CFRs at a dose of 0.3 mg/kg but with a significant prolongation of the bleeding time. Finally, the combination of 0.6 mg/kg 6B4-Fab and 0.1 mg/kg MA-16N7C2 fully prevented the CFRs without prolongation of the bleeding time. The present study demonstrates that the inhibition of platelet GP Ib function by 6B4-Fab is a powerful intervention to prevent platelet thrombus formation in injured arteries without prolongation of the bleeding time; the latter is in contrast to the result after the inhibition of GP IIb/IIIa. Moreover, we demonstrate that combining a GP Ib blocker with a GP IIb/IIIa blocker can achieve a strong antithrombotic effect without increasing the bleeding time. This provides new information that will be beneficial in designing clinical therapeutic approaches.

Key Words: platelet glycoprotein Ib • platelet glycoprotein IIb/IIIa • cyclic flow reductions • antithrombotic agents • bleeding time

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