Classification of inherited von Willebrand disease and implications in clinical practice

Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is caused by quantitative or qualitative deficiencies in von Willebrand factor (VWF). Diagnosis relies on clinical characteristics, such as bleeding symptoms and a family history of bleeding symptoms, and laboratory tests confirming reduced levels or activity of VWF. Several types of VWD have been identified that have distinct pathology, phenotype, and response to therapy. No single test provides sufficient information to classify the disorder, and multiple assays are needed. These assays can determine whether bleeding is caused by quantitative (types 1 and 3) or qualitative (type 2) deficiency in VWF activity. The presence or absence of high-molecular weight multimers of VWF can distinguish between types 2M and 2A VWD, respectively. Higher affinity for platelet glycoprotein Ibα receptors suggests type 2B, and poor affinity for factor VIII indicates type 2N VWD. Other tests, including molecular diagnostic techniques, may be used to confirm the diagnosis. Despite the apparent complexity surrounding the classification of VWD, accurate classification is achievable using the appropriate combination of laboratory assessments. Correct classification is essential to the management of patients with VWD because therapeutic decisions often depend on the specific type of disease.