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Blood ; 123(12): 1905-16, 2014 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-24443440

RESUMO

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.


Assuntos
Transtornos Plaquetários/sangue , Transtornos Plaquetários/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Desamino Arginina Vasopressina/farmacologia , Adolescente , Adulto , Idoso , Cálcio/sangue , Grânulos Citoplasmáticos/efeitos dos fármacos , Fator VIII/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas/metabolismo , Sódio/sangue , Trombina/biossíntese , Adulto Jovem , Fator de von Willebrand/metabolismo
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