Diagnosis and Treatment of von Willebrand Disease

Von Willebrand disease (vWD) is one of the most common, yet most complex, inherited bleeding disorders. A recent review identified advances in vWD diagnosis and treatment, including the following:

• 85% of patients have type 1 vWD, a partial deficiency of von Willebrand factor (vWF); the rare type 3 has complete deficiency of vWF.
• Patients with type 2 have a qualitative defect in vWF; type 2A patients have defective multimerization, type 2B patients have spontaneous platelet binding, type 2M patients have defective ligand binding, and type 2N patients have defective binding of factor VIII.
• Type 2A is often complicated by bleeding from gastrointestinal angiodysplasia.
• Bleeding assessment tools, available on the Web, can identify individuals who require evaluation for vWD or prophylaxis for bleeding.
• Common tests are measurements of vWF antigen and ristocetin cofactor; the latter is gradually being replaced by assaying the binding of vWF to modified glycoprotein Ib.
• Genotyping is most valuable for type 1 patients with vWF ≤30 IU/dL and for those with type 2 or 3; genotyping also detects a benign variant, D1472H, which affects ristocetin binding but not vWF function.
• Desmopressin is used to treat patients with mild to moderately severe type 1 vWD. A test dose is given by nasal spray (1.5 mg/mL) or intravenously or subcutaneously (0.3 µg/kg). Fluids are to be restricted for 24 hours following the dose to avoid hyponatremia.
• For severe bleeding or major surgery, plasma-derived or recombinant vWF is given in doses of 50 to 60 ristocetin cofactor units/kg, repeated every 12 to 24 hours as necessary; recombinant factor VIII is infused with the initial dose of recombinant vWF.
• Antifibrinolytics and hormonal therapy are also options for heavy menstrual bleeding.