Clinical and laboratory diagnosis of von Willebrand disease

von Willebrand disease (VWD) is a hereditary bleeding disorder first described by Erik von Willebrand in 1926. The disease is characterized by frequent bruising, bleeding from minor wounds, nosebleeds, heavy menstrual bleeding, bleeding after tooth extraction, gastrointestinal bleeding, and joint bleeds. The underlying cause of VWD was identified 45 years later as a deficiency of von Willebrand factor (VWF), a high-molecular-weight protein that circulates with factor VIII in plasma. The clinical diagnosis of VWD involves the presence of bleeding symptoms, detection of at least one abnormality of VWF function in laboratory tests, and demonstration of familial inheritance. VWD presents a broad spectrum of clinical and laboratory abnormalities, making the diagnostic process complex. Integrating clinical and laboratory data into the diagnostic pathway using a Bayesian approach can help build evidence for a diagnosis. Over the years, several diagnostic assays have been developed to measure the quantitative and qualitative properties of VWF. Automated laboratory assays for measuring VWF have been implemented in recent decades, and assessment tools for clinical evaluation of bleeding severity have been developed. Laboratory diagnosis involves screening and first-level diagnostic tests to measure VWF antigen, VWF-platelet binding activity, and factor VIII coagulant activity. Second-level subtyping tests are required to characterize the phenotypic defects of the type 2 variants and classify the patients. Proper diagnosis and classification of VWD are essential in order to recognize patients who may benefit from treatment, determine the optimal treatment modality, and prevent overdiagnosis.