Von Willebrand disease type 2

Von Willebrand disease type 2 (VWD type 2) is a group of qualitative defects of von Willebrand factor (VWF), a large glycoprotein essential for platelet adhesion and as a carrier for coagulation factor VIII. Unlike type 1 VWD, which involves a partial quantitative deficiency, type 2 VWD is characterized by dysfunctional VWF protein. It is further subdivided into four subtypes: type 2A (decreased VWF-dependent platelet adhesion with selective deficiency of high-molecular-weight VWF multimers), type 2B (increased affinity of VWF for platelet glycoprotein Ib, often causing thrombocytopenia), type 2M (decreased VWF-dependent platelet adhesion without selective loss of high-molecular-weight multimers), and type 2N (markedly decreased binding affinity of VWF for factor VIII, sometimes called autosomal hemophilia). The disease primarily affects the hemostatic system. Clinical manifestations typically include mucocutaneous bleeding such as easy bruising, prolonged bleeding from cuts, epistaxis (nosebleeds), menorrhagia (heavy menstrual bleeding), and excessive bleeding after dental procedures or surgery. Gastrointestinal bleeding may also occur, particularly in type 2A. In type 2B, mild thrombocytopenia may be present and can worsen during physiological stress such as pregnancy or surgery. Type 2N patients may present with symptoms resembling mild hemophilia A, including joint and soft tissue bleeding, due to reduced circulating factor VIII levels. Diagnosis involves specialized laboratory testing including VWF antigen levels, VWF ristocetin cofactor activity, VWF multimer analysis, VWF-factor VIII binding assays, and ristocetin-induced platelet aggregation studies. Genetic testing of the VWF gene on chromosome 12 can confirm the specific subtype. Treatment depends on the subtype and clinical situation. Desmopressin (DDAVP) may be effective in some type 2A and 2M patients but is generally contraindicated in type 2B due to the risk of worsening thrombocytopenia. VWF-containing factor VIII concentrates (such as plasma-derived VWF/FVIII concentrates) are the mainstay of treatment for bleeding episodes and surgical prophylaxis across most type 2 subtypes. Antifibrinolytic agents such as tranexamic acid may be used as adjunctive therapy, particularly for mucosal bleeding.

Common questions about Von Willebrand disease type 2