Artificial microvascular graft thrombosis: the consequences of platelet membrane glycoprotein Ib inhibition and thrombin inhibition

Abstract

Early thrombosis of artificial microvascular grafts (AMG, grafts < or = 2 mm internal diameter) prevents their reliable clinical use. The present studies were undertaken to examine the effect of hirudin, a thrombin-specific inhibitor, and of the F(ab')2 fragment of PG-1, a monoclonal antibody (MoAb) directed against guinea pig platelet membrane glycoprotein Ib (GPIb), on AMG patency in an animal model. One-centimeter long segments of expanded polytetrafluoroethylene (ePTFE), 0.88 mm internal diameter, were serially implanted as interposition grafts in the guinea pig femoral arterial systems bilaterally. A control group was treated with 0.5 mL saline intravenously (IV) 30 minutes before limb 1 and limb 2 graft implantation. Three experimental groups were treated with 0.5 mL saline IV before limb 1 graft implantation as an animal control and with either 0.5 mL saline containing 1.25 mg/kg IV PG-1 F(ab')2, (which inhibits ristocetin-induced platelet agglutination and von Willebrand factor binding), hirudin 1 mg/kg IV, or a combination of both agents before limb 2 graft implantation. GPIb inhibition, thrombin inhibition, and the combination resulted in a significant prolongation of AMG patency (P < .005). Whereas thrombin inhibition with hirudin prolonged AMG patency similar to that observed with GPIb inhibition, the combination of GPIb and thrombin inhibition provided the overall longest prolongation of AMG patency. These results indicate that both platelet membrane GPIb and thrombin play a role in AMG thrombosis.