What is the management of Von Willebrand disease?

Management of Von Willebrand Disease

Desmopressin (0.3 μg/kg IV) is the first-line treatment for Type 1 VWD patients with VWF and factor VIII levels ≥10 U/dL who demonstrate responsiveness on test infusion, while VWF/factor VIII concentrates are required for Type 3 and most Type 2 patients where desmopressin is ineffective. 1, 2, 3

Treatment Selection by VWD Type

Type 1 VWD (75% of cases)

• Desmopressin is the treatment of choice for Type 1 patients with factor VIII coagulant activity levels >5% 2, 4, 3
• Administer 0.3 μg/kg IV (maximum 28 μg) 30 minutes prior to procedures or for acute bleeding 1, 2
• Desmopressin stimulates endogenous VWF release from endothelial cells, increasing circulating VWF and factor VIII levels 3-6 fold within 30-90 minutes 1
• A test infusion must be performed first to confirm adequate response before relying on desmopressin for surgical coverage 4, 3
• Doses may be repeated at 12-24 hour intervals, but tachyphylaxis occurs after 3-5 doses due to depletion of endothelial VWF stores 1

Type 2 VWD (Qualitative Defects)

• VWF/factor VIII concentrates are the mainstay of treatment as desmopressin is ineffective in most Type 2 variants 4, 3
• Plasma-derived, virally inactivated concentrates containing both VWF and factor VIII should be used 4, 5
• Dosage should maintain factor VIII levels between 50-150 U/dL to balance efficacy against thrombotic risk 4

Type 3 VWD (Severe Deficiency)

• VWF/factor VIII concentrates are mandatory as these patients have virtually complete VWF deficiency 4, 5, 3
• Desmopressin is contraindicated in Type 3 VWD as there are no endothelial VWF stores to release 2, 5
• Patients with VWF antigen levels <1% are least likely to respond to any therapy except replacement 2

Perioperative and Procedural Management

Target Levels

• Maintain VWF activity ≥50 IU/dL throughout surgical procedures and the postoperative period 1
• For neuraxial anesthesia, VWF activity must be maintained at ≥50 IU/dL using desmopressin, VWF/factor VIII concentrates, or cryoprecipitate combined with tranexamic acid 1

Timing

• Administer desmopressin or concentrates 30 minutes prior to scheduled procedures 2, 4
• Continue replacement therapy for appropriate duration postoperatively based on procedure type and bleeding risk 4

Adjunctive Therapies

Antifibrinolytics

• Tranexamic acid should be used as appropriate in combination with primary therapy, particularly for mucosal bleeding and dental procedures 1

Specific Bleeding Scenarios

• For epistaxis: Apply firm sustained compression to lower third of nose for ≥5 minutes, followed by topical vasoconstrictors if needed 6
• Critical pitfall: Use only resorbable nasal packing in VWD patients; non-resorbable packing triggers rebleeding upon removal 1, 6

Monitoring and Dose Adjustment

• Check bleeding time, factor VIII coagulant activity, ristocetin cofactor activity, and VWF antigen during desmopressin administration to ensure adequate levels 2
• When using concentrates, monitor factor VIII levels to avoid sustained elevations >150 U/dL, which may increase postoperative venous thromboembolism risk 4
• Appropriate dosing intervals are critical for patients on secondary long-term prophylaxis for recurrent bleeding 4

Special Populations and Scenarios

Acquired von Willebrand Syndrome

• Requires multidisciplinary approach including minimizing anticoagulation and blood product replacement 1
• For refractory bleeding, restore high molecular weight VWF multimers using desmopressin, VWF-containing concentrates, or drugs preventing VWF proteolysis 1
• Treatment of underlying disorder may resolve acquired VWF deficiency 1

Patients on Antiplatelet Agents

• Desmopressin (0.3 μg/kg) is recommended for trauma patients with VWD who are treated with platelet-inhibiting drugs 7

Contraindications and Limitations

• Do not use desmopressin in patients with factor VIII levels ≤5%, hemophilia B, or factor VIII antibodies 2
• Desmopressin is ineffective in severe homozygous VWD with factor VIII and VWF antigen <1% 2
• Patients with abnormal molecular forms of factor VIII antigen should not receive desmopressin 2
• Factor VIII levels between 2-5% represent a gray zone requiring careful monitoring if desmopressin is attempted 2