ABSENCE OF EFFECT OF DDAVP INFUSION ON PLATELET GLYCOPROTEIN-IB IX AND GLYCOPROTEIN-IIB/IIIA COMPLEXES, AND THEIR INTERACTION WITH NEWLY RELEASED VON-WILLEBRAND-FACTOR/

Several possibilities have been raised to explain the beneficial effec t of 1-deamino-8-D-arginine vasopressin (DDAVP) in several hemostatic disorders but, so far, its exact mechanism(s) of action is still unkno wn. Aiming to throw new light on the problem, we have investigated: (a ) whether DDAVP induces platelet activation or quantitative/qualitativ e modifications of GPs Ib/IX and IIb/IIIa, and (b) the binding to thes e glycoprotein receptors of von Willebrand factor (vWF) purified from blood obtained before and after administration of DDAVP.Analysis of th e expression of GMP 140 and thrombospondin demonstrated no platelet ac tivation following administration of DDAVP. Binding assays and flow cy tometry with antibodies against GPs Ib/IX and IIb/IIIa, the study of t he ristocetin-dependent vWF binding, and immunoblotting with an anti-G PIb/IX antibody, demonstrated no quantitative or functional changes of these complexes after the infusion of DDAVP. Finally, native vWF puri fied from cryoprecipitate, and vWF purified from plasma of one DDAVP-i nfused volunteer, showed similar binding properties to GPIb/IX and GPI Ib/IIIa. These results suggest that DDAVP is quite inert on platelet g lycoproteins, and the drug-induced appearance of 'supranormal' high mo lecular weight vWF multimers seems not to modify the interaction of vW F with its main platelet receptors.