Absence of Effect of DDAVP Infusion on Platelet Glycoprotein Ib/IX and IIb/IIIa Complexes, and their Interaction with Newly Released von Willebrand Factor

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Abstract
Several possibilities have been raised to explain the beneficial effect of l-deamino-8-D-arginine vasopressin (DDAVP) in several hemostatic disorders but, so far, its exact mechanism(s) of action is still unknown. Aiming to throw new light on the problem, we have investigated: (a) whether DDAVP induces platelet activation or quantitative/qualitative modifications of GPs Ib/IX and IIb/IIIa, and (b) the binding to these glycoprotein receptors of von Willebrand factor (vWF) purified from blood obtained before and after administration of DDAVP. Analysis of the expression of GMP 140 and thrombospondin demonstrated no platelet activation following administration of DDAVP. Binding assays and flow cytometry with antibodies against GPs Ib/IX and IIb/IIIa, the study of the ristocetin-dependent vWF binding, and immunoblotting with an anti-GPIb/IX antibody, demonstrated no quantitative or functional changes of these complexes after the infusion of DDAVP. Finally, native vWF purified from cryoprecipitate, and vWF purified from plasma of one DDAVP-infused volunteer, showed similar binding properties to GPIb/IX and GPIIb/IIIa. These results suggest that DDAVP is quite inert on platelet glycoproteins, and the drug-induced appearance of 'supranormal' high molecular weight vWF multimers seems not to modify the interaction of vWF with its main platelet receptors.