What is the management and treatment for Von Willebrand (VWD) disease?

Management and Treatment for Von Willebrand Disease (VWD)

The management of Von Willebrand Disease requires a targeted approach based on disease type, with desmopressin being first-line therapy for Type 1 VWD and VWF-containing concentrates being essential for Type 3 and most Type 2 variants. 1, 2

Disease Classification and Clinical Presentation

• VWD is the most common inherited bleeding disorder, affecting males and females equally, with prevalence up to 1% of the general population 3
• Clinical manifestations include easy bruising, nosebleeds, mucosal bleeding, heavy menstrual bleeding, gastrointestinal bleeding, and increased bleeding risk with surgery or trauma 3, 1
• Three main types of VWD exist:
  • Type 1: Partial quantitative deficiency (~75% of cases) 3
  • Type 2: Qualitative deficiency with four subtypes (2A, 2B, 2M, 2N) 3
  • Type 3: Complete quantitative deficiency (rare, ~1 in 1,000) 3
• Acquired von Willebrand Syndrome (AVWS) can occur in association with various medical conditions and requires different management approaches 3

Treatment Strategies

Desmopressin (DDAVP)

• First-line treatment for Type 1 VWD patients with factor VIII levels >5% 4, 2
• Mechanism: Stimulates release of stored VWF from endothelial cells 3
• Dosing: 0.3 μg/kg intravenously 3, 4
• Administration timing: 30 minutes prior to scheduled procedures 4
• Clinical effects:
  • Increases circulating VWF and factor VIII levels 3-6 fold within 30-90 minutes 3
  • Can maintain hemostasis during surgical procedures 4
  • Effective for spontaneous bleeding episodes in responsive patients 4, 2
• Limitations:
  • Tachyphylaxis may occur after 3-5 doses due to depletion of VWF stores 3
  • Not effective in Type 3 VWD and most Type 2 variants 4, 2
  • Not recommended for severe VWD with factor VIII and VWF antigen levels <1% 4

VWF-Containing Concentrates

• Essential for Type 3 VWD and most Type 2 variants where desmopressin is ineffective 2
• Available as plasma-derived or recombinant products 1, 2
• For major surgeries, maintain FVIII or VWF levels >0.50 IU/mL for at least 3 consecutive days 5
• Current virucidal-treated concentrates are effective and safe 2
• May not always correct bleeding time defect completely 2

Adjunctive Therapies

• Tranexamic acid:
  • Antifibrinolytic agent that can reduce bleeding complications 5
  • Particularly effective when combined with VWF replacement 5
• Topical hemostatic agents: Useful for accessible bleeding sites 1
• Hormonal therapies: Can help manage menorrhagia in women with VWD 1
• For nosebleeds:
  • Apply firm sustained compression to lower third of nose for ≥5 minutes 6
  • Consider topical vasoconstrictors if bleeding continues 6
  • Use resorbable nasal packing if necessary (avoid non-resorbable packing) 6

Perioperative Management

• For major surgeries:
  • Maintain FVIII/VWF levels >0.50 IU/mL for at least 3 days 5
  • Hemostatic efficacy is excellent in 74-100% of cases with this approach 5
• For minor procedures:
  • Combination of tranexamic acid with VWF level increase to 0.50 IU/mL is more effective than VWF increase alone 5
• Product selection depends on:
  • VWD type and subtype 7
  • Nature and invasiveness of procedure 7
  • Patient's previous response to treatment 7

Special Considerations

• Acquired VWD requires treatment of underlying condition when possible 3
• Low VWF (30-50 IU/dL) patients may have significant bleeding despite mild reduction:
  • Tranexamic acid and desmopressin are both effective options 8
  • Bleeding phenotype correlates poorly with VWF levels in these patients 8
• Patients with blood group O have VWF levels 25% lower than other blood groups 3
• Pregnancy, estrogen, and inflammatory conditions can elevate VWF levels 3

Common Pitfalls to Avoid

• Misdiagnosis due to variable bleeding symptoms and external modifiers 1
• Using non-resorbable nasal packing in VWD patients (removal may trigger additional bleeding) 6
• Failing to account for blood group when interpreting VWF levels 3
• Attempting desmopressin in patients unlikely to respond (Type 3, severe Type 1) 4, 2
• Not monitoring VWF and FVIII levels during treatment to ensure adequate response 4