title: Desmopressin (DDAVP) improves recruitment of activated platelets to collagen but simultaneously increases platelet endothelial interactions in 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.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Hannover Medical School , Hannover , Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Calmer
authors.forename: Annika
authors.initials: A
authors.lastname: Ferkau
authors.forename: Jan
authors.initials: J
authors.lastname: Larmann
authors.forename: Kai
authors.initials: K
authors.lastname: Johanning
authors.forename: Eliana
authors.initials: E
authors.lastname: Czaja
authors.forename: Christian
authors.initials: C
authors.lastname: Hagl
authors.forename: Frank
authors.initials: F
authors.lastname: Echtermeyer
authors.forename: Lilia
authors.initials: L
authors.lastname: Goudeva
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Heuft
authors.forename: Gregor
authors.initials: G
authors.lastname: Theilmeier
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor; D003094:Collagen; D003894:Deamino Arginine Vasopressin