Management of Von Willebrand Disease
The management of Von Willebrand Disease (VWD) requires a targeted approach based on disease type, with desmopressin being first-line therapy for Type 1 VWD and VWF-containing concentrates for Type 2 and Type 3 VWD to prevent and treat bleeding episodes. 1
Disease Classification and Diagnosis
VWD is the most common inherited bleeding disorder, affecting approximately 1% of the population, with clinically significant bleeding in about 1:10,000 individuals. The disease is classified into three main types:
- Type 1 (75% of cases): Partial quantitative deficiency of VWF
- Type 2 (most remaining cases): Qualitative deficiency with four subtypes (2A, 2B, 2M, 2N)
- Type 3 (rare, ~1:1,000): Virtually complete quantitative deficiency 1
Additionally, Acquired Von Willebrand Syndrome (AVWS) can develop in association with certain medical conditions or treatments, such as ECMO support 1.
Treatment Algorithm
1. Type 1 VWD (VWF levels >5%)
- First-line therapy: Desmopressin (DDAVP) 0.3 μg/kg IV 2
2. Type 2 VWD
- Type 2A, 2M, 2N: VWF-containing concentrates (plasma-derived or recombinant)
- Type 2B: VWF-containing concentrates (desmopressin contraindicated in most cases due to risk of thrombocytopenia)
- Selected Type 2 variants: Desmopressin may be effective in some subtypes and should be tested 4
3. Type 3 VWD (VWF levels <5%)
- Primary therapy: VWF-containing concentrates only
- Desmopressin ineffective due to absence of VWF stores 3
4. Acquired VWD Syndrome (AVWS)
- Treat underlying condition when possible
- For bleeding management: Similar approach as hereditary VWD based on severity
- In ECMO patients: Multidisciplinary approach with minimizing anticoagulation and blood product replacement 1
Adjunctive Therapies
Antifibrinolytic agents (e.g., tranexamic acid):
- Particularly effective for mucosal bleeding
- Used as prophylaxis for minor (71%) and major (59%) surgeries 1
- Can be used alone or in combination with other treatments
Topical hemostatic agents for accessible bleeding sites
Hormonal therapies for menorrhagia in women 5
Treatment Based on Clinical Scenario
Minor Bleeding or Procedures
- Type 1 VWD: Desmopressin 0.3 μg/kg IV 30 minutes prior to procedure 2
- Type 2/3 VWD: VWF-containing concentrates
- All types: Consider antifibrinolytics as adjunctive therapy
Major Surgery or Severe Bleeding
Type 1 VWD:
- First attempt: Desmopressin if previously responsive
- If inadequate: Add VWF-containing concentrates
Type 2/3 VWD: VWF-containing concentrates with monitoring of VWF:RCo, FVIII levels
Heavy Menstrual Bleeding
- First-line: Combined oral contraceptives
- If persistent: Consider tranexamic acid, desmopressin, or VWF concentrates based on VWD type
- Refractory cases: Consider hormonal IUD or surgical options 1
Special Considerations
Pregnancy and childbirth: VWF levels often increase during pregnancy but fall rapidly postpartum. Close monitoring and prophylactic treatment may be needed, especially postpartum 1
Pediatric patients: Similar management approach as adults, with dose adjustments
Elderly patients: May have higher baseline VWF levels due to age but still require treatment based on clinical bleeding
Monitoring Treatment
- Laboratory monitoring: VWF:RCo activity, FVIII levels, bleeding time
- Clinical response: Cessation of bleeding, prevention of surgical bleeding
Common Pitfalls to Avoid
- Failure to test desmopressin responsiveness before therapeutic use
- Overuse of desmopressin leading to tachyphylaxis or hyponatremia
- Inadequate dosing of VWF concentrates for major procedures
- Neglecting adjunctive therapies like antifibrinolytics
- Misdiagnosis of VWD type leading to inappropriate treatment selection
By following this structured approach to VWD management based on disease type, severity, and clinical scenario, clinicians can effectively prevent and treat bleeding episodes while minimizing complications and improving patient quality of life.