What is the treatment for von Willebrand disease?

Treatment for von Willebrand Disease

The treatment of von Willebrand disease should be tailored based on disease type, with desmopressin (DDAVP) at 0.3 μg/kg being the first-line therapy for type 1 and some type 2 variants, while VWF/FVIII concentrates are recommended for type 2B, type 3, and cases unresponsive to desmopressin. 1, 2

Disease Classification and Treatment Selection

• Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting approximately 1 in 100 people 3
• Treatment approach depends on disease type and severity:
  • Type 1 (80% of cases): Characterized by mild to moderate quantitative deficiency of VWF 3
  • Type 2 (various subtypes): Qualitative defects in VWF function 2
  • Type 3: Severe quantitative deficiency with very low or undetectable VWF levels 3

First-Line Treatment Options

Desmopressin (DDAVP)

• Standard dosing: 0.3 μg/kg diluted in 50 ml saline and infused over 30 minutes 1

• Mechanism: Increases endogenous release of VWF and Factor VIII from cellular compartments 2, 4

• Indications:

  • First-line therapy for type 1 VWD 1, 3
  • Some patients with type 2A VWD 1, 2
  • Mild hemophilia A with FVIII levels at least 5% of normal 5

• Administration routes:

  • Intravenous infusion (most common in hospital settings) 6
  • Subcutaneous injection (suitable for home treatment) 6

• Contraindications:

  • Type 2B VWD (can induce platelet aggregation and thrombocytopenia) 7, 4
  • Type 3 VWD (typically unresponsive) 3, 4

VWF/FVIII Concentrates

• Indications:

  • First-line therapy for type 2B, 2M, 2N, and type 3 VWD 1, 8
  • Patients unresponsive to desmopressin 9, 3
  • Cases requiring higher or sustained VWF levels 9

• Administration considerations:

  • Dosing should achieve a minimum of 30% of plasma factor concentration 1
  • Human-derived medium-purity FVIII concentrates complexed to VWF (e.g., Humate-P) are preferred for type 2B VWD 8

Treatment Protocol

1. Initial Assessment:

   • Perform desmopressin trial at diagnosis to establish individual response patterns 4
   • Target VWF activity of ≥50 IU/dL for most procedures 1

2. For Type 1 VWD:

   • Administer desmopressin 0.3 μg/kg IV over 30 minutes 1, 2
   • For home treatment of minor bleeding episodes, subcutaneous desmopressin can be used 6
   • Monitor for response (correction of bleeding time and FVIII levels) 5

3. For Type 2 VWD:

   • Type 2A: Trial desmopressin; use if responsive 1, 2
   • Type 2B, 2M, 2N: Use VWF/FVIII concentrates 1, 8
   • Monitor clinical response and laboratory parameters 5

4. For Type 3 VWD:

   • VWF/FVIII concentrates are required 3
   • Desmopressin is ineffective 3, 4

5. For Unresponsive Cases or Major Bleeding:

   • Switch to VWF/FVIII concentrates if desmopressin is inadequate 9
   • Consider adjunctive treatments like tranexamic acid 2

Safety Considerations

• Desmopressin adverse effects:

  • Fluid retention and hyponatremia (requires fluid restriction) 7
  • Facial flushing, headache, and tachycardia in about 30% of treatments 6
  • Risk of seizures with extreme decrease in plasma osmolality 7
  • Rare thromboembolic events 2

• VWF/FVIII concentrates:

  • Modern virally-attenuated products have excellent safety profiles 9, 3
  • May not always correct bleeding time defects completely 3

Special Considerations

• For pregnant patients with VWD requiring neuraxial anesthesia, target VWF activity ≥50 IU/dL for spinal anesthesia or epidural catheter removal in patients with mild bleeding history 1
• For patients with severe bleeding history, target VWF activity ≥80 IU/dL 1
• Cryoprecipitate may be used if VWF/FVIII concentrates are unavailable, but carries higher infectious risk 9, 3
• Home therapy with subcutaneous desmopressin has shown 94% excellent/good response rates for appropriate candidates 6