Desmopressin (DDAVP) improves recruitment of activated platelets to collagen but simultaneously increases platelet endothelial interactionsin vitro

Abstract

Platelet dysfunction can cause clinically relevant bleeding. Treatment with DDAVP is advocated for this condition. DDAVP increases von Willebrand factor (VWF) on endothelial cells (ECs) and in plasma. VWF could facilitate platelet deposition on subendothelial collagen. VWF also facilitates platelet/EC interactions. Therefore DDAVP could precipitate thromboembolic events. We used a flow chamber model to study in vitro and ex vivo if DDAVP alters recruitment of platelets to EC and collagen. Resting or TRAP-activated platelets and EC were treated individually or simultaneously with 0.4 ng/ml DDAVP. Fluorophor-labeled platelets (10(6)/ml) were resuspended in reconstituted blood and superfused across EC and collagen in an in vitro flow chamber model at arterial shear (320 s(-1)). Adhesion of platelets to the respective surface was recorded fluorescence microscopically and platelet covered area was assessed. TRAP significantly induced adhesiveness of platelets for collagen and EC. DDAVP pretreatment of platelets did not affect adhesiveness of resting or TRAP-activated platelets for collagen or EC. Adhesiveness of resting but not TRAP-activated platelets was induced on DDAVP-treated EC. DDAVP-conditioned EC supernatant contained vWF and significantly increased platelet deposition on collagen. Platelets from patients with clinically suspected platelet dysfunction undergoing aortic valve replacement exhibited decreased platelet deposition on collagen surfaces. In summary, our data confirm that DDAVP can induce release of platelet adhesion promoting factors from EC, which is most likely vWF. DDAVP has no direct effect on platelets. Blood samples from DDAVP-treated patients do not exhibit significantly augmented platelet deposition on collagen ex vivo. This influence of released promoting factors might cause an increase of undesirable interactions of platelets with EC.

Collagen‐mediated hemostasis

“…For instance, desmopressin (1‐deamino‐8‐ d ‐arginine vasopressin) has been successfully used as a hemostatic agent in collagen vascular disorders such as Ehlers–Danlos syndrome (EDS) and Marfan syndrome . Desmopressin is an endothelial activating agent that improves recruitment of activated platelets to collagen, thereby improving platelet–endothelial interaction . It exerts its hemostatic effect by increasing the plasma levels of von Willebrand factor (VWF), factor VIII, and tissue‐type plasminogen activator.…”

Administration of the vasopressin analog desmopressin for the management of bleeding in rectal cancer patients: results of a phase I/II trial

“…In addition, a marked increase of platelet adhesiveness has been described as part of the hemostatic mechanisms exerted by dDAVP. Since the compound has no direct effects on platelets, it seems that dDAVP can induce the release of a platelet adhesion factor from endothelial cells, which is presumably VWF [25].…”

Assessment and management of coagulopathy in neurocritical care

“…DDAVP use has also been demonstrated to improve platelet function in patients on COX-1 and ADP receptor inhibitors in several tests of platelet function compared to those who had not received reversal agents [3,50,51,[65][66][67][68]. Clinically, it has been shown to reduce blood loss and improve hemostasis in patients with aspirin exposure undergoing cardiac surgery [49,69,70].…”