Heparin cofactor II inhibits thrombus formation in a rat thrombosis model

Heparin cofactor II is postulated to be an extravascular thrombin inhibitor that is physiologically stimulated by dermatan sulfate. However, the role of heparin cofactor II has not yet been clearly demonstrated in vivo. In th is study, we estimated the antithrombotic effect of heparin cofactor II adm inistered exogenously in a rat model of thrombosis. Thrombus was induced in the rat femoral artery by endothelial damage due to the photochemical reac tion between systemically injected rose bengal and transillumination with g reen light. Pretreatment with heparin cofactor II significantly prolonged t he time required to occlude the femoral artery (occlusion time) in a dose-d ependent manner. At an effective dose in this thrombosis model, heparin cof actor II did not prolong the activated partial thromboplastin time and the prothrombin time in normal rats. Argatroban, a selective synthetic thrombin inhibitor, significantly prolonged the occlusion time. However, argatroban also prolonged the activated partial thromboplastin time and prothrombin t ime at an effective dose. These results suggest that the administration of heparin cofactor II in vivo effectively inhibited thrombus formation on the vessel walls whose endothelium is damaged without a prolongation of the co agulation time while heparin cofactor II may also inhibit the thrombin acti vity in the subendothelial tissue in vivo. (C) 2000 Elsevier Science Ltd. A ll rights reserved.