von Willebrand factor

vWF is produced by vascular endothelial cells and megakaryocytes, stored in Weibel-Palade bodies and platelet alpha-granules, and released upon vascular injury or stimulation (e.g., by desmopressin/DDAVP, epinephrine, or thrombin). It performs two critical functions: (1) it binds exposed subendothelial collagen at sites of vascular injury and links to platelet GpIb receptors, mediating platelet adhesion (primary hemostasis) independent of platelet activation; (2) it binds and stabilizes Factor VIII in plasma, protecting it from proteolytic degradation, thus indirectly supporting the coagulation cascade (secondary hemostasis).

vWF multimers vary in size, with larger multimers being hemostatically most active. ADAMTS13 cleaves ultra-large vWF multimers into smaller, less thrombogenic forms; deficiency of ADAMTS13 (genetic or acquired via autoantibodies) causes thrombotic thrombocytopenic purpura (TTP), characterized by microvascular thrombi from uncleaved ultra-large vWF multimers.

Von Willebrand disease (vWD) is the most common inherited bleeding disorder (autosomal dominant in most types), resulting from quantitative (Type 1 partial deficiency, Type 3 severe/complete deficiency) or qualitative (Type 2, various subtypes with dysfunctional multimers) defects in vWF. Clinically, it presents with mucocutaneous bleeding (epistaxis, gingival bleeding, menorrhagia, easy bruising) rather than deep tissue hematomas typical of hemophilia, since vWF's primary role is platelet adhesion. Laboratory findings include prolonged bleeding time/PFA-100, normal platelet count, possibly prolonged PTT (due to low Factor VIII), and decreased vWF antigen/activity (ristocetin cofactor assay). Ristocetin induces vWF binding to platelet GpIb, and the ristocetin cofactor assay measures functional vWF activity.

Treatment includes desmopressin (DDAVP), which stimulates release of stored vWF from endothelial cells (useful in Type 1), or vWF-containing Factor VIII concentrates for more severe disease or Type 3.

Clinically important associations include: vWF is also relevant in Bernard-Soulier syndrome (defective GpIb receptor, so vWF cannot bind platelets despite normal vWF) and Glanzmann thrombasthenia (defective GpIIb/IIIa, affecting platelet aggregation but not vWF-mediated adhesion).