von Willebrand disease: a laboratory approach.

ABSTRACT

von Willebrand disease (VWD) is a common inherited bleeding disorder. Accurate diagnosis and classification of VWD is crucial for clinical management. A detailed clinical history, including that of bleeding, is required. A family and drug history are also important. Genetic factors such as blood group, and environmental factors such as stress, trauma, pregnancy and inflammation should also be considered. The age, ethnic group and hormonal status could also affect the von Willebrand factor (VWF) levels. No single test is robust enough to detect all variants of VWD. In view of the heterogeneity of the disease and limitations in assays, a battery of tests should be performed before a final diagnosis can be reached. These include the screening coagulation tests, factor VIIIC assay, VWF antigen assay, assessment of functional VWF which includes VWF ristocetin cofactor assays, VWF collagen binding assay, ristocetin-induced platelet aggregation and VWF multimer analysis. The newer ELISA techniques based on VWF binding with factor VIII glycoprotein (Gp) 1b and cerebrosides have also helped in determining certain unusual forms of VWD. The advent of new systems such as platelet function analysers (PFA), thromboelastography (TEG) and clot signature analysers (CSA), which are designed to assess either the primary platelet function or as a global haemostasis screen, have facilitated and simplified the diagnosis. However, few centres all over the world can perform all these expensive tests to provide a final diagnosis of VWD. We reviewed the laboratory investigations required for a diagnosis of VWD. Apart from congenital VWD, the possibility of acquired VWD should be considered in those with a negative past history of bleeding or in the presence of an underlying disease.