Inhibition of platelet glycoprotein Ib, glycoprotein IIb/IIIa, or both by monoclonal antibodies prevents arterial thrombosis in baboons.

Abstract

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.

• Authors: Dongmei Wu, Muriel Meiring, Harry F Kotze, Hans Deckmyn, Nancy Cauwenberghs
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 22 Issue 2 Pg. 323-8 (Feb 01 2002) ISSN: 1524-4636 [Electronic] United States
• PMID: 11834536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Blood Proteins
• Platelet Glycoprotein GPIIb-IIIa Complex
• Platelet Glycoprotein GPIb-IX Complex
• platelet adhesion inhibitor

Topics

• Animals
• Antibodies, Monoclonal (blood, pharmacology)
• Blood Proteins (pharmacology)
• Dose-Response Relationship, Drug
• Female
• Femoral Artery
• Male
• Papio
• Platelet Aggregation (drug effects)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)
• Platelet Glycoprotein GPIb-IX Complex (antagonists & inhibitors)
• Thrombosis (drug therapy)