Von Willebrand disease type 3

Von Willebrand disease type 3 (VWD type 3) is the most severe form of von Willebrand disease, a hereditary bleeding disorder caused by a virtually complete deficiency of von Willebrand factor (VWF). VWF is a large glycoprotein that plays two critical roles in hemostasis: it mediates platelet adhesion to damaged blood vessel walls and serves as a carrier protein for coagulation factor VIII (FVIII), protecting it from premature degradation. In type 3 VWD, VWF levels are undetectable or extremely low (typically less than 1–3% of normal), and FVIII levels are also markedly reduced (usually 1–10% of normal), resulting in a combined defect in both primary and secondary hemostasis. Patients with VWD type 3 typically present in early childhood with severe mucocutaneous bleeding, including frequent and prolonged nosebleeds (epistaxis), gum bleeding, heavy menstrual bleeding (menorrhagia) in women, and prolonged bleeding from cuts or after dental procedures and surgery. Unlike milder forms of VWD, type 3 patients may also experience joint bleeding (hemarthrosis) and muscle hematomas similar to those seen in severe hemophilia A, due to the significantly reduced FVIII levels. Gastrointestinal bleeding can also occur and may be particularly challenging to manage. Life-threatening bleeding episodes, including intracranial hemorrhage, have been reported. Treatment of VWD type 3 centers on replacement therapy with plasma-derived concentrates containing both VWF and FVIII (VWF/FVIII concentrates), which are used for the prevention and treatment of bleeding episodes and for surgical prophylaxis. Desmopressin (DDAVP), which is effective in milder forms of VWD, is generally ineffective in type 3 because there are no endogenous VWF stores to release. Some patients benefit from regular prophylactic infusions of VWF/FVIII concentrates, particularly those with recurrent joint or gastrointestinal bleeding. Antifibrinolytic agents such as tranexamic acid may be used as adjunctive therapy. Notably, some patients with type 3 VWD may develop alloantibodies (inhibitors) against VWF after repeated exposure to replacement products, which can complicate treatment and, in rare cases, lead to anaphylactic reactions.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Von Willebrand disease type 3