Von Willebrand disease (VWD) is caused by quantitative and/or qualitative defects of the von Willebrand factor (VWF), a multimeric high molecular glycoprotein. Typically, it affects the primary haemostatic system, which is reflected by a mucocutaneous bleeding tendency simulating a functional platelet defect. The VWF promotes its function in two ways: It promotes platelet adhesion to the injured vessel wall under conditions of high shear forces and it functions as carrier for factor VIII in plasma. Due to its complexity diagnosis of VWD is one of the most challenging of coagulation disorders. The stepwise diagnosis of VWD includes patient's and family history, orientating procedures (bleeding time, filter tests, platelet count, aPTT), confirmatory tests (VWF:Ag, VWF:RCo, VIII:C) and tests for final classification (VWF:CB, RIPA, multimeric analysis, bWF:FVIIIB, platelet VWF). Accumulating knowledge of the different clinical phenotypes and their pathophysiological basis was translated into a classification scheme that differentiated between quantitative and qualitative defects by means of quantitative and functional parameters and by analyzing the electrophoretic pattern of VWF multimers. The advent of molecular techniques provided the opportunity for genotype/phenotype studies which recently helped not only to elucidate or confirm important functions of VWF and the steps of its posttranslational processing but also many disease causing defects.
