The effect of DDAVP infusion on thrombin generation in platelet-rich plasma of von Willebrand type 1 and in mild haemophilia A patients

In von Willebrand disease (VWD) type 1 and mild haemophilia A patients we s tudied the effect of an infusion of DDAVP (0.3 mu g/kg body weight) on thro mbin generation in platelet-rich plasma (PRP) and platelet-poor plasma (PPP ). Baseline thrombin generation in PRP was diminished both in the haemophil ia A and vWD patients. It was normal in vWD plasma when sufficient procoagu lant phospholipids were present, tither via adding phospholipid vesicles to PPP or via scrambling of the platelet membrane with ionomycin in PRP. In h aemophilia A plasma, thrombin generation did not normalize by providing pro coagulant phospholipids. Treatment with DDAVP temporarily restored thrombin generation in PRP to normal in both diseases. To investigate the individual roles of von Willebrand factor (VWF) and fact or VIII. we also studied the effect of factor VIII infusion on thrombin gen eration in a severe haemophilia patient. It appears that tit a fixed normal VWF concentration, <25% factor VIII is sufficient for normal thrombin gene ration in PRP. At a sufficient factor VIII concentration, however, thrombin generation is still lower than normal in VWD patients: similar to 40% of V WF is required for half-normal thrombin generation in PRP. It thus appears that VWF is also a clotting factor, in the sense that it is required for normal thrombin generation. This underlines the importance of the interaction between coagulation and thr platelets in normal haemostasi s. Thrombin generation in PRP appears to be a suitable test to reflect the combined function.