von Willebrand Disease
GENERAL PRINCIPLES
Classification
• vWD has three main types42:
î Type 1 vWD, due to a quantitative deficiency of vWF (70%-80% of cases)
î Type 2 vWD, due to a qualitative defect of vWF, includes four subtypes (2A, 2B, 2M, 2N):
#9632; Type 2A: reduced vWF high molecular weight multimer
#9632; Type 2B: pathologically enhanced platelet affinity to vWF
#9632; Type 2M: reduced platelet affinity to vWF
#9632; Type 2N: defective FVIII binding to vWF
î Type 3 vWD, due to a near complete lack of vWF.
Epidemiology
vWD, the most common inherited bleeding disorder, affects around 0.1%-1% of the population.
Etiology
Most forms of vWD have an autosomal dominant inheritance with variable penetrance, although autosomal recessive forms (types 2N and 3) exist. vWF circulates as multimers of variable size and facilitate adherence of platelets to injured vessel walls and stabilize FVIII in plasma.
DIAGNOSIS
Clinical Presentation
Clinical findings consist of mucocutaneous bleeding (epistaxis, menorrhagia, gastrointestinal bleeding), easy bruising, and bleeding from trauma or surgery.
Diagnostic Testing
Testing for suspected vWD should include vWF:Ag, vWF:RCo and FVIII activity. See American Society of Hematology pocket guide on vWD.
TREATMENT
• Goal of therapy is to raise vWF:RCo and factor VIII activity to ensure adequate hemostasis. vWF:RCo activities gt;50% control most hemorrhages.43
• DDAVP 0.3 #956;g#8725;kg IV can be used to treat type 1 vWD. Because only two-thirds of patients will respond, a test dose should assess for a response. For responders undergoing minor invasive procedures, infuse 1 hour before, followed by q12-24h for three more doses postoperatively as needed, with or without oral antifibrinolytic drugs (i.e., aminocaproic acid or tranexamic acid).
î DDAVP does not effectively treat most type 2 or type 3 vWD patients.
î DDAVP is contraindicated in type 2B vWD because of the risk of thrombocytopenia.
î Common side effects of DDAVP include hyponatremia, nausea, and flushing. Patients should limit fluid intake to 1200 mL/d within 24 hours of any dose.
• vWF plasma-derived concentrate transfusions (Alphanate, Humate-P, and Wilate) and recombinant vWF (Vbnvendi) should aim to raise vWF:RCo activity to ~100% and maintain it between 50% and 100% until sufficient hemostasis occurs (typically 5-10 days).
• Recombinant vWF (Vdnvendi) is now FDA-approved for control of bleeding episodes and perioperative management of bleeding in adults with von Willebrand disease.
• Indications for concentrate transfusions
î Type 1 vWD-DDAVP nonresponders î Type 1 vWD-major bleeding or surgery î All other vWD types requiring hemostasis treatment