Enhancement of the Haemostatic Effect of Platelets in the Presence of High Normal Concentrations of Von Willebrand Factor

Von Willebrand Factor (vWF) is a key protein mediating platelet adhesion on the surface of damaged endothelia, initiating platelet-platelet aggregation and supporting platelet activation. It plays also an important role in protecting FVIII from early activation and clearance . The product's included coagulation factor VIII acts in in the activated form like the regular factor VIIIa. It takes part in the coagulation amplification by activating factor X to Xa together with factor IVa. Activation of factor X results in generating thrombin out of prothrombin. Wilate® is approved in Switzerland for prophylaxis and treatment of bleeding in patients suffering from von Willebrand disease and Haemophilia A.

VWF is produced by the endothelial cells as a heterogeneous mixture of low and high molecular weight units. VWF is a ligand for receptors on the platelet surface and endothelial cells (GP1b-V-IX, αIIbβ3, αvβ3) mediating adhesion of platelets to each other or to the endothelium. Initial platelet adhesion is a crucial step in haemostatic functioning. Loss of platelets, vWF or blocking of these integrins due to the wide use of platelet aggregation inhibitors can cause bleeding. In case of severe blood loss, these conditions often result in mass transfusion.

There is suggestive evidence from an in-vitro flow chamber model and from treatment of patients with severe vWF deficiency that increasing the concentration of vWF onto normal or high normal levels can enhance platelet adhesion independent from platelet count. This might translate into a better haemostatic effect of administered platelet concentrates in the bleeding patient and less need for transfusion of blood products (platelet concentrates), especially in clinical conditions with a high probability of low platelet count and low vWF activities (e.g., heart surgery with extracorporeal circulation, ECMO).

To the best of our knowledge, no trial exists that investigated the effect of platelet transfusion in combination with the administration of balanced vWF in severe blood loss. The investigators hypothesize that simultaneous transfusion of platelets and balanced (1:1 vWF and FVIII) vWF compared to placebo reduces the overall need of transfusion of blood products.