Past, Present, and Future of von Willebrand Disease

von Willebrand disease (vWD) is the most common inherited bleeding disorder. Various subtypes of vWD exist as either quantitative deficiencies or qualitative defects of the von Willebrand factor (vWF) protein and lead to an array of bleeding manifestations. Individuals with vWD typically have increased mucocutaneous bleeding including oral mucosal bleeding, epistaxis, and heavy menstrual bleeding. Other common bleeding manifestations including petechiae, easy bruising, surgical-related bleeding, postpartum hemorrhage, and trauma-induced bleeding. In more severe subtypes gastrointestinal bleeding, hemarthrosis, and intramuscular bleeding can occur. Given the spectrum of bleeding phenotypes, management can differ greatly from one individual to the next with the majority of individuals receiving on-demand treatment while more severely affected individuals may receive long-term prophylaxis. Common on-demand therapeutics include oral, intravenous, topical, and/or intranasal antifibrinolytics, intravenous, subcutaneous and/or intranasal desmopressin, and intravenous plasma-derived and recombinant-vWF replacement therapy. Long-term prophylactic regimens include hormonal therapies and regularly scheduled infusions of plasma-derived and recombinant-vWF concentrates. Over the past 100 years the therapeutic landscape for individuals with vWD has changed significantly and continues to evolve. There are numerous studies currently underway to evaluate new treatments including several drugs administered via subcutaneous injection, and vagal nerve stimulation. Historically individuals with vWD have poorer health-related quality of life and higher healthcare resource utilization compared to the general population, emphasizing the ongoing need for improved therapeutics.