What is the primary treatment for Von Willebrand disease?

From the Guidelines

The primary treatment for Von Willebrand disease is desmopressin (DDAVP), which can be administered as a nasal spray or intravenously at doses of 0.3 mcg/kg, as it stimulates the release of von Willebrand factor (VWF) and factor VIII from endothelial cell storage sites, temporarily increasing their levels in the bloodstream. This approach is based on the understanding of VWD as outlined in the 2008 NHLBI/NIH guidelines 1, which describes VWD as a condition characterized by a deficiency or dysfunction of von Willebrand factor (VWF), a multimeric plasma glycoprotein crucial for platelet adhesion and aggregation at sites of vascular injury.

Treatment Approaches

• For minor bleeding episodes or before minor procedures, a single dose of DDAVP is often sufficient.
• More significant bleeding may require doses every 12-24 hours for 2-3 days.
• However, DDAVP is not effective for all types of Von Willebrand disease, particularly Type 3 and some variants of Type 2, as noted in the guidelines 1.
• In these cases, or for severe bleeding episodes, VWF replacement therapy using VWF concentrates is necessary, with dosing typically ranging from 40-60 IU/kg depending on the severity of bleeding.

Adjunctive Therapy

• For long-term management, antifibrinolytic medications like tranexamic acid may be used, especially for mucosal bleeding, at doses of 1-1.5 g orally three times daily.
• Patients should avoid aspirin and NSAIDs as these can worsen bleeding tendencies, a consideration that is crucial for managing the quality of life and reducing morbidity in patients with VWD.

Disease Types and Management

• The three main types of VWD are Type 1 (partial quantitative deficiency), Type 2 (qualitative deficiency) with four subtypes, and Type 3 (virtually complete quantitative deficiency) 1.
• Type 1 VWD accounts for ~75% of symptomatic persons, and nearly all the remaining affected persons have Type 2 variants, with Type 2A more common than types 2B, 2M, or 2N.
• Type 3 VWD is rare, affecting only ~1 person in 1,000, and requires more aggressive management strategies, including VWF replacement therapy.

From the FDA Drug Label

Desmopressin acetate injection 4 mcg/mL is indicated for patients with mild to moderate classic von Willebrand’s disease (Type I) with factor VIII levels greater than 5% Desmopressin acetate injection will often maintain hemostasis in patients with mild to moderate von Willebrand’s disease during surgical procedures and postoperatively when administered 30 minutes prior to the scheduled procedure Desmopressin acetate injection will usually stop bleeding in mild to moderate von Willebrand’s patients with episodes of spontaneous or trauma-induced injuries such as hemarthroses, intramuscular hematomas or mucosal bleeding

The primary treatment for Von Willebrand disease (Type I), specifically mild to moderate cases with factor VIII levels greater than 5%, is desmopressin acetate injection. This treatment can help maintain hemostasis during surgical procedures and postoperatively, as well as stop bleeding in cases of spontaneous or trauma-induced injuries 2.

• Key points:
  • Desmopressin acetate injection is indicated for mild to moderate von Willebrand’s disease (Type I)
  • Factor VIII levels should be greater than 5% for effective treatment
  • Treatment can help with hemostasis and bleeding control in various situations

From the Research

Overview of Von Willebrand Disease Treatment

• Von Willebrand disease (vWD) is the most common hereditary bleeding disorder, characterized by a dual hemostatic defect due to defective platelet adhesion-aggregation and abnormal coagulation due to Factor VIII (FVIII) deficiency 3.
• The primary goal of treatment is to correct this dual defect and restore hemostatic function.

Treatment Options

• Desmopressin (DDAVP) is the treatment of choice for type 1 vWD, as it increases endogenous release of FVIII and von Willebrand factor (vWF) 3, 4.
• In patients unresponsive to DDAVP, plasma-derived VWF-containing FVIII concentrates are the preferred treatment 5.
• VWF/FVIII concentrates can be used to restore hemostatic function in patients with type 3 vWD and in some cases of type 2 vWD 5, 6.

Considerations for Treatment

• The choice of treatment depends on several factors, including the severity of the bleed, the procedure planned, the subtype and severity of the disease, and the age and morbidity of the patient 3.
• Dosing and timing of VWF:FVIII concentrates are important and depend on the nature of the surgical procedure 3, 5.
• Antifibrinolytic treatment can be used as an adjunct to replacement therapy during minor or major surgery involving mucosal surfaces 3.
• Laboratory monitoring of efficacy and safety issues, such as thrombosis risk and thromboprophylaxis, are important considerations for the use of VWF-containing concentrates 5.