How we make an accurate diagnosis of von Willebrand disease

摘要

von Willebrand disease (VWD) is a common autosomally inherited hemorrhagic disorder mainly associated with mucocutaneous bleeding. VWD is due to quantitative (type 1 and 3) or qualitative (type 2) defects of von Willebrand factor (VWF), a large multimeric plasma glycoprotein that plays a relevant role in hemostasis. VWF is essential to mediate platelet adhesion and aggregation at the sites of vascular injury under high shear stress conditions. VWF also carries coagulation factor VIII (FVIII), prolonging its half-life and concentrating it at the site of the damaged endothelium. The diagnosis of VWD, in agreement with the International Society for Thrombosis and Hemostasis guidelines, requires several assays that are necessary to evaluate the capacity of VWF to interact with several ligands, e.g. platelet glycoprotein Ib alpha, collagen and FVIII. Therefore, the differential diagnosis of VWD patients as type 1, 2A, 2B, 2M, 2N or 3 is a prerogative of specialized laboratories, where specific tests, like multimer analysis or ristocetin-induced platelet agglutination, are performed routinely. On the other hand, the basic identification of patients with VWD is nowadays possible in many hemostasis laboratories thanks to the availability of automated tests that measure in patient plasma VWF antigen levels and its plateletdependent activity. Nevertheless the laboratory investigation for VWD of a subject referred for a hemorrhagic tendency should start only after the attending physician, after evaluation of his/her personal and family bleeding history, confirmed the suspicion for VWD. The purpose of this manuscript is to give an overview of the complex process that leads to the diagnosis of the VWD.