Controlled trial of desmopressin in liver cirrhosis and other conditions associated with a prolonged bleeding time

Abstract

The synthetic vasopressin derivative desmopressin (DDAVP) shortens a prolonged bleeding time (BT) in patients with uremia, congenital platelet dysfunction, and von Willebrand disease. To establish the limits of the clinical usefulness of DDAVP, a controlled randomized study was carried out in 53 patients and ten volunteers with different conditions that have in common a prolonged BT. DDAVP significantly shortened the BT in 21 cirrhotics (P less than .01), in eight patients with unclassified prolonged BT (P less than .05) and in ten volunteers taking the antiplatelet drugs aspirin (P less than .05) and ticlopidine. The BT changes were not statistically significant in 15 patients with severe thrombocytopenia nor in nine with congenital platelet dysfunction, even though a few patients with storage pool deficiency responded with a marked BT shortening. Our findings indicate that DDAVP might be given when biopsies or other surgical procedures must be carried out in patients with prolonged BT. However, the compound is often ineffective in patients with thrombocytopenia or congenital platelet dysfunction.

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

“…It is well known that desmopressin shortens the bleeding time in aspirin-treated individuals [4,5], but the duration of the effect of desmopressin on Fig. 2.…”

“…Ruggeri et al [7] postulated that large vWF multimers transiently released by desmopressin from cellular compartments might enhance platelet adhesion and potentiate primary haemostasis. Mannucci et al [5], however, found that additional factors must be invoked to explain the haemostatic effectiveness of desmopressin, because although large vWF multimers were found in all patients after desmopressin, the bleeding time was not shortened in all. Beck et al [8] found no direct stimulation of platelets by desmopressin, and believed the effect of desmopressin on the prolonged bleeding time in aspirin treated patients to be only secondary to the increased plasma concentration of vWF.…”

Randomized controlled trial of desmopressin plus terlipressin vs. terlipressin alone for the treatment of acute variceal hemorrhage in cirrhotic patients: A multicenter, double-blind study

“…In this study, we attempted to improve the performance of vasoactive drugs in controlling variceal hemorrhage in cirrhotic patients by improving the hemostasis abnormalities that are present in these patients and may contribute to initiation or maintenance of variceal hemorrhage. Therefore we compared a standard treatment with terlipressin with a combination of terlipressin plus DDAVP, which is an effective nonspecific hemostatic agent (15,16) that has been shown to improve the bleeding and partial thromboplastin times in cirrhotics for 4 to 6 hr after intravenous infusion (13,14).…”

“…Of the current medical alternatives to endoscopic variceal sclerotherapy, vasopressin induces transient increases of some clotting factors (10, 111, and terlipressin (12) and somatostatin have no effect. On the other hand, 1-deamino-8-D-arginine vasopressin (DDAW, desmopressin), a synthetic analog of the antidiuretic hormone L-argmine vasopressin, shortens bleeding time (a measure of primary hemostasis) and partial thromboplastin time (a measure of intrinsic coagulation) and increases levels of factor VIII and von Willebrand factor in cirrhotic patients for 4 to 6 hr after its intravenous infusion (13)(14). In addition, DDAW has been successfully used as a nonspecific hemostatic agent to reduce blood loss during surgery in patients with normal hemostatic function (15, 16).…”

Desmopressin (DDAVP) in the treatment of bleeding disorders: the first twenty years

“…There is usually mild or moderate thrombocytopenia, but platelet counts do not correlate negatively with the bleeding time. Factor VIII and vWF are in the high normal range, or even higher, yet intravenous desmopressin shortens the bleeding time of cirrhotic patients [45,46]. However, a controlled clinical trial has shown that desmopressin is not useful in the management of acute variceal bleeding in cirrhotic patients [47].…”