Desmopressin treatment improves platelet function under flow in patients with postoperative bleeding

Abstract

Summary. Background: Patients undergoing major cardiothoracic surgery are subjected to dilution, owing to massive fluid infusion and blood component transfusion. These patients may experience bleeding perioperatively, and are frequently treated with the endothelium-activating agent desmopressin. Objectives: To investigate the effect of desmopressin administration on von Willebrand factor (VWF)-dependent coagulant and platelet functions under flow conditions. Patients/methods: Blood from 16 patients with postoperative bleeding was obtained before and after desmopressin treatment (0.3 lg kg À1 body weight), and assessed for coagulant properties and platelet function. Furthermore, VWF antigen levels and multimer composition were determined in both samples. Results: Desmopressin treatment did not change thrombin generation in plasma or whole blood thromboelasticity. Also coagulation factor levels (other than factor VIII) and coagulation times were unchanged, suggesting that desmopressin treatment did not have a major effect on the coagulant activity. On the other hand, desmopressin treatment raised the already high plasma levels of VWF from a median of 116 IU mL À1 (interquartile range [IQR] 102-154 IU mL À1 ) to a median of 160 IU mL À1 (IQR 126-187 IU mL À1 ) (P = 0.007), owing to accumulation of the high molecular weight VWF multimers. Furthermore, desmopressin treatment caused an increase in collagendependent thrombus formation and platelet phosphatidylserine exposure. Markers of thrombus formation correlated with the plasma levels of VWF. In vitro control experiments confirmed a major contribution of VWF to thrombus formation and procoagulant activity under conditions of blood dilution. Conclusions: Desmopressin treatment of patients with bleeding complications after cardiothoracic surgery induces the release of high molecular weight VWF multimers, which enhance platelet activation and thrombus formation under flow conditions.

Low COAT platelets are frequent in patients with bleeding disorders of unknown cause (BDUC) and can be enhanced by DDAVP

“…23 In patients with primary platelet function defects, we have demonstrated that desmopressin (1-deamino-8-D-arginine vasopressin [DDAVP]) is able to selectively increase procoagulant COAT platelets. 23 This observation has been replicated in patients in whom DDAVP was given because of increased bleeding during cardiac surgery 24 and is confirmed by our current experience. In the period from January 2015 to August 2021, we have electively tested DDAVP in 53 adult patients, including primary platelet function defects, von Willebrand disease, or BDUC, finding a relative increase of ≥5% COAT platelets in 83% (n = 44) of them, as observed in our previous cohort.…”

“…Confirming our previous results, we observed a decreased ability to generate COAT platelets (<25%) in 27% (n = 10): in four of 14 with nondiagnostic LTA and LA, and in six of 23 with a normal workup. Overall, in our three cohorts we found 36 patients with decreased procoagulant COAT platelets among 157 patients provisionally classified as having BDUC, suggesting a prevalence of 23% (95% confidence interval [20][21][22][23][24][25][26][27].…”

Desmopressin for treatment of platelet dysfunction and reversal of antiplatelet agents: a systematic review and meta‐analysis of randomized controlled trials

“…Desmopressin (also known as DDAVP or 1‐deamino‐8‐D‐arginine vasopressin) has been used for the treatment of congenital bleeding disorders for almost four decades. It acts by increasing plasma von Willebrand factor, factor VIII and intracellular platelet calcium/sodium ion concentrations, and by increasing formation of procoagulant platelets and platelet adhesion to collagen under flow . Desmopressin is also recommended in a number of guidelines for treatment of bleeding in patients with platelet dysfunction or on antiplatelet agents , but there has been no formal/systematic review of the size of the benefit and the risks of desmopressin in the context of antiplatelet therapy.…”

The effect of desmopressin and tranexamic acid on blood product use and postoperative bleeding after emergent isolated coronary artery bypass grafting (CABG) surgery

“…[16,17] Intracellular platelet calcium/ sodium ion concentrations are increased by desmopressin by increasing the procoagulant platelet formation and platelet adhesion to collagen under flow. [17][18][19] It also increases the platelet functions [20], and used especially in von Willebrand insufficiency and hemophilia patients. [6] Platelet dysfunction because of antiplatelet drugs increases the risk of bleeding.…”