Increased thrombogenesis and embolus formation in mice lacking glycoprotein V

The glycoprotein (GP) Ib-V-IX complex plays a critical role in initiating p latelet adhesion to von Willebrand factor (VWF) at the site of vascular inj ury. The complex also forms a high-affinity binding site for thrombin, Usin g an intravital microscopy mouse model, it was previously established that vWF plays a critical role in mediating platelet adhesion and thrombus forma tion following mesenteric arteriolar injury induced by ferric chloride. Fur ther characterization of this model showed that these thrombotic events wer e also thrombin dependent. Using this vWF-and thrombin-dependent model, thi s study shows that GP V gene deficiency significantly accelerates both plat elet adhesion and thrombus formation in mice following arteriolar injury. T he time required for vessel occlusion in GP V-deficient (GP V-/-) mice was significantly shorter than that in wild-type mice. Interestingly, large emb oli were also produced in GP V-/- mice, but not in wild-type mice, causing frequent downstream occlusion. However, when the 2 genotypes were compared in the in vitro perfusion chamber where thrombin was inhibited by heparin, no significant differences were found in either initial single-platelet adh esion or thrombus volume. These results demonstrate that GP V-/- mice have accelerated thrombus growth in response to vascular injury and suggest that this is caused by enhanced thrombin-induced platelet activation rather tha n enhanced binding of GPIb-V-IX to vWF, Absence of GP V also compromises th rombus stability. (C) 2001 by The American Society of Hematology.