The effect of desmopressin on platelet function: a selective enhancement of procoagulant COAT platelets in patients with primary platelet function defects.
1-deamino-8-d-arginine vasopressin (desmopressin [DDAVP]) is clinically efficacious in patients with mild platelet function disorders but it is not known which mechanisms mediate this effect. Our aim was to evaluate the impact of in vivo DDAVP administration in these patients. We assessed von Willebrand factor (VWF), factor VIII, platelet activation and aggregation, platelet-dependent thrombin generation, and platelet intracellular Na(+)/Ca(2+) fluxes, before and 2 and 4 hours after DDAVP (0.3 µg/kg). We found (1) no significant changes for P-selectin expression, PAC-1 binding, δ-granule content and secretion, and platelet-aggregation; (2) significant decreases of secretion of α-granules and GPIIb-IIIa activation induced by adenosine 5'-diphosphate, convulxin, and thrombin; (3) significant increases of procoagulant platelets induced by convulxin/thrombin and platelet-dependent thrombin generation; and (4) significant increases of intracellular Na(+)/Ca(2+) concentrations. We show that in vivo DDAVP selectively and markedly enhances the ability to form procoagulant platelets and increases platelet-dependent thrombin generation by enhancing Na(+)/Ca(2+) mobilization. This report indicates that the beneficial hemostatic effect of DDAVP is not limited to an increase in large VWF multimers. An enhancement of platelet procoagulant activity appears to be an additional and (at least in platelet disorders) -possibly clinically relevant mechanism of DDAVP's action.
Department of Haematology and Central Haematology Laboratory, Inselspital, Bern University Hospital and University of Bern, Switzerland.
Giuseppe
G
Colucci
Monika
M
Stutz
Sophie
S
Rochat
Tiziana
T
Conte
Marko
M
Pavicic
Marianne
M
Reusser
Evelyne
E
Giabbani
Anh
A
Huynh
Charles
C
Thürlemann
Peter
P
Keller
Lorenzo
L
Alberio
D000293:Adolescent; D000328:Adult; D000368:Aged; D001791:Blood Platelet Disorders / Q000097:blood* / Q000188:drug therapy*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D003594:Cytoplasmic Granules / Q000187:drug effects; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D012964:Sodium / Q000097:blood; D013917:Thrombin / Q000096:biosynthesis; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism
D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D005169:Factor VIII; D012964:Sodium; D013917:Thrombin; D003894:Deamino Arginine Vasopressin; D002118:Calcium