Von Willebrand disease type 2M

Von Willebrand disease type 2M (VWD type 2M) is a qualitative variant of von Willebrand disease characterized by decreased platelet-dependent function of von Willebrand factor (VWF) that is not caused by the loss of high-molecular-weight VWF multimers. In this subtype, the VWF protein is produced in normal amounts and retains its full multimer distribution, but carries mutations that impair its ability to bind to platelet glycoprotein Ib (GPIb) or to collagen in the subendothelium. This results in defective primary hemostasis — the process by which platelets adhere to injured blood vessel walls to form an initial plug. VWD type 2M is caused by mutations in the VWF gene located on chromosome 12. Patients with VWD type 2M typically present with mucocutaneous bleeding symptoms, including easy bruising, prolonged bleeding from cuts or dental procedures, epistaxis (nosebleeds), menorrhagia (heavy menstrual bleeding) in women, and excessive bleeding after surgery or trauma. The severity of bleeding can vary considerably among affected individuals, even within the same family. Laboratory findings characteristically show a disproportionately low ristocetin cofactor activity (VWF:RCo) relative to VWF antigen levels, with a normal multimer pattern — a key distinguishing feature from VWD type 2A, which shows loss of high-molecular-weight multimers. Treatment of VWD type 2M depends on the severity of bleeding and the clinical context. Desmopressin (DDAVP) may be trialed, as some patients show a partial response with increased VWF release from endothelial stores, though the released VWF remains functionally impaired. For patients who do not respond adequately to DDAVP or who require major surgical coverage, VWF-containing plasma-derived factor concentrates are the mainstay of treatment. Antifibrinolytic agents such as tranexamic acid may be used as adjunctive therapy, particularly for mucosal bleeding or dental procedures. Hormonal therapies may help manage menorrhagia in affected women. Genetic counseling is recommended for affected families.

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