Glycoprotein V-deficient platelets have undiminished thrombin responsiveness and do not exhibit a Bernard-Soulier phenotype

Adhesion of platelets to extracellular matrix via von Willebrand factor (vW F) and activation of platelets by thrombin are critical steps in hemostasis . Glycoprotein (GP) V is a component of the GPIb-V-IX complex, the platelet receptor for vWF. GPV is also cleaved by thrombin. Deficiency of GPIb or G PIX results in Bernard-Soulier syndrome (BSS), a bleeding disorder in which platelets are giant and have multiple functional defects. Whether GPV-defi ciency might also cause BSS is unknown as are the roles of GPV in platelet- vWF interaction and thrombin signaling. We report that GPV-deficient mice d eveloped normally, had no evidence of spontaneous bleeding, and had tail bl eeding times that were not prolonged compared with wild-type mice. GPV-defi cient platelets were normal in size and structure as assessed by flow cytom etry and electron microscopy. GPV-deficient and wild-type platelets were in distinguishable in botrocetin-mediated platelet agglutination and in their ability to adhere to mouse vWF Al domain. Platelet aggregation and ATP secr etion in response to low and high concentrations of thrombin were not decre ased in GPV-deficient platelets compared with wild-type. Our results show t hat (1) GPV is not necessary for GPIb expression and function in platelets and that GPV deficiency is not likely to be a cause of human BSS and (2) GP V is not necessary for robust thrombin signaling. Whether redundancy accoun ts for the lack of phenotype of GPV-deficiency or whether GPV serves subtle or as yet unprobed functions in platelets or other cells remains to be det ermined. (C) 1999 by The American Society of Hematology.