Effects of desmopressin on platelet membrane glycoproteins and platelet aggregation in volunteers on clopidogrel

Abstract

Purpose: The use of clopidogrel is standard in interventional cardiology. Haemorrhage occurs in some patients, which implies a need for a non-transfusional therapy. Desmopressin showed its efficacy as an antidote of acetylsalicylic acid. In this trial the effects of desmopressin on platelet glycoproteins and the platelet's ability to aggregate under the influence of clopidogrel are studied.Methods: The trial was conducted as an open, prospective, single-centre, randomised pilot study with n = 17 healthy volunteers in a parallel-group design. 1 h after an oral loading dose of 375 mg clopidogrel the effects of a single-dose of 300 µg of Octostim ® nasal spray (n = 9) on platelet aggregation, activity of platelets on the density of membrane-bound receptors are measured.Results: Ristocetin cofactor and platelet reactivity rose significantly after the administration of Octostim ® nasal spray with 31.9% and 5.3%, respectively (p = 0.0329; p = 0.0414). The ADP-induced platelet aggregation increased after the administration of Octostim ® nasal spray by approximately 20% (p = 0.0564). The fraction of CD62-and CD63-positive platelets did not change after clopidogrel nor after desmopressin (p = 0.4203; p = 0.6774). The density of GPIIb/IIIa receptors per platelet did not change after desmopressin (p = 0.9652). The density of GPIb/IX receptors per platelet rose after desmopressin without reaching the level of significance (p = 0.0802). In the desmopressin group alone the receptor density rose by 5.5% (p = 0.0783).Conclusion: The administration of desmopressin improved the primary haemostasis when given in addition to a clopidogrel therapy. Patients undergoing a heart catheter procedure with clopidogrel might benefit from the use of desmopressin when having a bleeding episode.

Guideline on the management of bleeding in patients on antithrombotic agents

“…Desmopressin shortened the bleeding time in healthy volunteers after exposure to clopidogrel (Mannucci et al, 1986;Leithauser et al, 2008) but safety concerns in patients with cardiovascular disease usually prevent use. Mixing platelets treated with P2Y12 antagonists ex vivo with untreated donor platelets restored abnormal platelet aggregation responses although a higher proportion of donor platelets was required than for correction of the aspirin effect (Vilahur et al, 2007;Li et al, 2012).…”

Desmopressin (DDAVP) in the management of patients with congenital bleeding disorders

“…DDAVP increases the expression of glycoprotein Ib/IX and CD62 (P‐selectin) on platelet surfaces, leading to increased platelet rolling, activation and adhesion . Collectively, these actions can shorten the bleeding time and normalize shear‐induced platelet aggregation .…”

Periprocedural Coagulation Status in Percutaneous Interventions

“…No specific reversal agent is available; however, both platelet infusion and desmopressin can be helpful. 38 Clopidogrel is withheld five days before any category interventions. Ticlopidine and prasugrel are withheld 5 days before category I interventions and 7 days before category II and III interventions.…”