Why use DDAVP in von Willebrand dz?
to reverse platelet dysfunction
VWF is a complex multimeric glycoprotein with two important roles in haemostasis: it binds to platelet receptors, bridging them to other platelets and subendothelial tissue that is exposed after vascular injury, and also acts as a carrier protein for the coagulation factor VIII (FVIII), thus preventing its proteolytic inactivation in the plasma.
VWF is released into plasma as a large multimer, which is instantaneously broken down by a protease into several molecules of varying molecular sizes: multimers with high, intermediate and low molecular weight.
The high‐molecular‐weight multimers, by virtue of their strong affinity to platelet receptors, are considered more potent than the other multimers. The absence of these multimers leads to a defect in platelet adhesion, prolonging the bleeding time. Ristocetin is an antibiotic that enhances the interaction between the VWF and the platelet receptors. On the basis of this effect, ristocetin cofactor activity test is used as a surrogate marker of the functional activity of the VWF
Vasopressin is a secretagogue of VWF. This hormone functions through two receptors, termed V1 and V2, which activate different intracellular second messengers.7 Agonist activity at V2 receptors leads to a rise in intracellular concentrations of cyclic adenosine monophosphate, which in turn induces exocytosis of VWF from its storage sites.
Desmopressin (1‐desamino‐8‐d‐arginine vasopressin, also abbreviated DDAVP) is a synthetic analogue of vasopressin, which activates only V2 receptors and thus lacks its vasoconstrictor and uterotonic properties. Intravenous or intranasal administration of desmopressin to healthy individuals is followed by a rise in levels of both VWF and its precious cargo, FVIII.2 Individuals who lack V2 receptors—that is, patients with nephrogenic diabetes insipidus—expectedly do not show this increase in VWF and FVIII levels.