Lack of effect of 1-desamino-8-D-arginine vasopressin on direct adhesion of platelets to collagen

Abstract

Administration of 1-desamino-8-D-arginine vasopressin (DDAVP), a synthetic vasopressin derivative, causes an increase in plasma factor VIII and von Willebrand factor (vWF). Recently, evidence has become available that intravenous infusion of DDAVP shortens the prolonged bleeding times in some patients with primary platelet defects even though their plasma levels of vWF and FVIII are normal prior to drug administration. The mechanism of this effect of DDAVP has not been well defined and it has been generally considered that the beneficial effect on the bleeding time is related to the rise in plasma vWF and its impact on platelet adhesion to subendothelial components including collagen, an important step in hemostasis. Thus, studies aimed at understanding the effect of DDAVP have focused on vWF-mediated adhesion of platelets to the subendothelium. For example, Sakariassen et al studied the platelet adherence to human arterial subendothelium and concluded that DDAVP improves hemostasis by causing enhanced vWF-mediated platelet adherence. This mechanism would explain the shortening of the bleeding time in patients with milder forms of vWD with subnormal levels of vWF. But patients with congenital platelets defects have normal plasma vWF raising the possibility that there may be other mechanisms contributing to the beneficial effect of DDAVP. It is clear that platelets can interact directly with collagen, mediated by specific platelet binding sites. Further, DDAVP binds to platelets even though by itself does not activate them. The present investigation was designed to elucidate whether DDAVP had any effect on the direct adhesion of platelets to collagen in the absence of mediation by vWF. Hashemi et al have suggested that the effect of DDAVP on endothelial cell release of vWF is mediated by an as yet uncharacterized intermediate factor(s) released from peripheral mononuclear cells. Therefore, we studied the effect also of plasma samples obtained from patients treated with DDAVP on adhesion of platelets to collagen.