What is the treatment for Von Willebrand Disease (VWD)?

Treatment of Von Willebrand Disease (VWD)

The treatment of Von Willebrand Disease should be tailored based on disease type, with desmopressin being effective for most Type 1 VWD patients, while VWF-containing factor concentrates are required for Type 2 and Type 3 VWD patients. 1, 2

Disease Classification and Treatment Approach

• VWD is classified into three main types with varying severity: Type 1 (~75% of cases with mild bleeding), Type 2 (variable bleeding severity), and Type 3 (severe, potentially life-threatening bleeding) 3
• Treatment strategies depend on accurate identification of these subtypes 1

Type 1 VWD (Mild Disease)

• Desmopressin (DDAVP) is the first-line treatment for most patients with Type 1 VWD 1, 4
• Desmopressin works by stimulating the release of stored VWF from endothelial cells, increasing circulating VWF and factor VIII levels 3-6 fold within 30-90 minutes 5
• Standard intravenous dosing is 0.3 μg/kg (maximum 28 μg) 5
• Doses may be repeated at 12-24 hour intervals, but tachyphylaxis may occur after 3-5 doses due to depletion of endothelial VWF stores 5

Type 2 and Type 3 VWD (Moderate to Severe Disease)

• VWF-containing factor VIII concentrates are the mainstay of treatment for Type 2 and Type 3 VWD patients 1, 2
• Humate-P (a factor VIII/VWF concentrate) has been FDA-approved specifically for VWD treatment 1, 6
• Dosing should be based on VWF:ristocetin cofactor (VWF:RCo) activity rather than factor VIII levels 6
• For urgent bleeding episodes, a median loading dose of 67.0 IU/kg VWF:RCo (range 25.7-143.2 IU/kg) followed by maintenance doses of approximately 74.0 IU/kg (range 16.4-182.9 IU/kg) has shown excellent/good efficacy in 98% of cases 6

Special Clinical Scenarios

Surgical Management

• For neuraxial anesthesia in VWD patients, VWF activity levels should be maintained at ≥50 IU/dL 5
• VWF activity levels can be achieved through desmopressin, VWF/FVIII concentrates, or cryoprecipitate, combined with tranexamic acid as appropriate 5
• For patients undergoing surgery, VWF activity should be maintained above 50 IU/dL for the duration of the procedure and postoperative period 5

Acquired Von Willebrand Syndrome (AVWS)

• AVWS, particularly in ECMO patients, requires a multidisciplinary approach 5
• Management includes minimizing anticoagulation and using blood product replacement 5
• For refractory bleeding, targeted treatments to restore high molecular weight VWF multimers include desmopressin, VWF-containing concentrates, or drugs that prevent VWF proteolysis 5

Important Precautions

• Desmopressin should NOT be used in Type 2B VWD as it may induce platelet aggregation 7
• Fluid restriction is recommended with desmopressin to prevent hyponatremia, which can be fatal if not properly managed 7
• Patients receiving desmopressin should be monitored for signs of hyponatremia: headache, nausea/vomiting, decreased serum sodium, weight gain, restlessness, fatigue, lethargy, disorientation, depressed reflexes, loss of appetite, irritability, muscle weakness, and abnormal mental status 7
• Antifibrinolytic therapy (e.g., tranexamic acid) is an important adjunct to replacement therapy during surgeries involving mucosal surfaces 4

Mechanism of Action and Rationale

• VWF serves two critical hemostatic functions: mediating platelet adhesion at sites of vessel injury and carrying/stabilizing factor VIII in circulation 8
• Treatment aims to correct both the platelet adhesion defect (causing mucosal bleeding and bruising) and the secondary factor VIII deficiency 8, 4
• The severity of bleeding correlates with the degree of VWF deficiency, explaining why different treatment approaches are needed based on disease type 3