Bioequivalence of von Willebrand factor-containing concentrates: implications for the choice in patients with von Willebrand disease. A position paper from the Italian Association of Hemophilia Centers

Von Willebrand disease (VWD) is a bleeding disorder caused by quantitative and/or qualitative defects of von Willebrand factor (VWF), a multimeric glycoprotein synthesized by endothelial cells and megakaryocytes. VWF plays a crucial role in hemostasis by mediating platelet adhesion to the sub-endothelium, platelet-platelet aggregation, and by acting as the carrier protein for circulating factor VIII (FVIII) in plasma, protecting it from early proteolytic degradation. The treatment and prevention of bleeding episodes in VWD patients requires the administration of either VWF/FVIII or purified VWF-containing concentrates when desmopressin (DDAVP) is contraindicated or ineffective. Many VWF/FVIII-containing concentrates, one purified plasma-derived VWF (pd-VWF) and one recombinant VWF (rVWF) product are available. These products are characterized by different manufacturing methods, variable VWF/FVIII ratio and multimers composition and content, which could influence their hemostatic efficacy. With this as background, the Italian Association of Hemophilia Centers (AICE) established a multidisciplinary expert panel to analyze the available literature evidences about the bioequivalence of the different licensed VWF-containing products. The data retrieved and their implications for therapeutic choices are discussed in this manuscript, which AICE endorsed as a position paper.