Effect kinetics of desmopressin‐induced platelet retention in healthy volunteers treated with aspirin or placebo

Abstract

Desmopressin is often used for haemostatic treatment in platelet dysfunction, but the effect kinetics of platelet responses and the mechanism of action are poorly known. This study aimed to determine the kinetics of platelet function responses induced by desmopressin in healthy volunteers treated with aspirin or placebo. Another aim was to correlate platelet responses to changes of von Willebrand factor (vWF) in plasma. We measured platelet function with a glass bead retention test, Ivy bleeding time, vWF:Ag and multimeric structure in plasma. Median baseline platelet retention was 12% (normal reference range 16-27%) during aspirin treatment and 18% during placebo. Median peak platelet retention after desmopressin was 33% during aspirin treatment and 34% during placebo. After about 3 h platelet function had returned to baseline. A second desmopressin dose after 3 h stimulated platelet retention to a similar extent as the first dose. There was no correlation between platelet responses and quantitative or qualitative changes of vWF in plasma. Platelet count did not change significantly. Thus, desmopressin's effect on platelet function lasts for about 3 h, but may be prolonged by a second dose immediately thereafter. These findings may have important clinical implications for patients with aspirin-induced platelet dysfunction undergoing surgery.

NXY‐059 Does Not Affect Bleeding Time in Healthy Volunteers: A Randomized, Double‐Blind, Placebo‐Controlled, 3‐Period Crossover Phase I Study

“…There was no significant difference for desmopressin in the ED 50 values induced by collagen, compared with either NXY‐059 or placebo. Desmopressin significantly increased platelet adhesion compared with placebo and NXY‐059, which was expected, based on published observations 18 …”

“…With 30 subjects, the power of a 1‐sided level of 10% t test in the appropriate linear model to detect the 35% reduction in bleeding time (desmopressin compared with placebo) reported by Lethagen et al 18 is at least 90%.…”

“…NXY‐059 (or placebo) was administered as a 1‐hour loading dose, followed by a 7‐hour maintenance dose, and the appropriate dose was calculated using individual creatinine clearance (CL crea ) estimated from the formula developed for males 17 . Desmopressin (or placebo) was administered as a single 10‐minute intravenous injection 6 hours 45 minutes ± 5 minutes after the start of infusion with NXY‐059 (or placebo), at a dose of 0.3 μg/kg body weight, based on previous observations 18 . If desmopressin did not have a significant shortening effect on bleeding time, the study would be considered inconclusive.…”

Intraleucocyte platelet‐activating factor levels in desmopressin‐treated patients with haemophilia A and von Willebrand disease

“…Mannucci showed that DDAVP has no direct effect on platelet count or aggregation, but enhances platelet adhesion to the vessel wall [1]. Lethagen et al [24] also showed that the effect of DDAVP on platelet adhesion may not be secondary to the vWF increase. It has been known that another relevant mechanism that accounts for the haemostatic effect of DDAVP is mediated by the release of high-molecular-weight multimers of vWF in endothelial cells [3,4].…”

The use of haemostatic drugs in haemophilia: desmopressin and antifibrinolytic agents

“…This effect lasts approximately 3 hours, although the platelets can be stimulated again. The effect on platelet adhesion seems to be independent of the increase in the plasma vWF levels [10]. Desmopressin also shortens the activated partial thromboplastin time (APTT) and the bleeding time [11].…”