Management of Von Willebrand Disease
Desmopressin (DDAVP) at a dose of 0.3 μg/kg is the first-line treatment for patients with mild to moderate Type 1 von Willebrand disease, while VWF-containing factor concentrates are recommended for Type 2B, Type 3, and severe forms of Type 1 and 2 VWD. 1, 2
Classification and Diagnosis
Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting approximately 1% of the general population, though clinically significant cases are less common.
Initial laboratory evaluation should include:
- Complete blood count with platelet count
- Prothrombin time (PT)
- Activated partial thromboplastin time (aPTT)
- Fibrinogen
- VWF screening panel including:
- VWF antigen (VWF:Ag)
- VWF ristocetin cofactor activity (VWF:RCo)
- Factor VIII coagulant activity (FVIII:C)
- VWF:RCo/VWF:Ag ratio (typically <0.5-0.7 in qualitative defects) 1
Treatment Approach by VWD Type
Type 1 VWD (Partial Quantitative Deficiency)
- First-line therapy: Desmopressin (DDAVP) 0.3 μg/kg IV diluted in 50 ml saline and infused over 30 minutes 2
- After administration, VWF and FVIII levels typically increase 3-6 fold within 30-90 minutes 2
- Doses may be repeated at 12-24 hour intervals, but tachyphylaxis may occur after 3-5 doses 2
- For patients unresponsive to DDAVP or with severe Type 1, use VWF-containing factor concentrates 3, 4
Type 2 VWD (Qualitative Defects)
- Type 2A, 2M: Trial of DDAVP first; many will require VWF-containing factor concentrates 4
- Type 2B: VWF-containing factor concentrates are the treatment of choice 1
- DDAVP is contraindicated as it may worsen thrombocytopenia 1
- Type 2N: Treat similarly to mild hemophilia A 1
Type 3 VWD (Complete Deficiency)
Specific Clinical Scenarios
Surgery and Invasive Procedures
- Target VWF:RCo levels:
- Major procedures: ≥80-100 IU/dL 1
- Minor procedures: ≥50 IU/dL
- For Type 1 responsive to DDAVP: Administer 30 minutes prior to procedure 6
- For Types 2B, 3, and severe Type 1 or 2: Use VWF-containing factor concentrates 1
- Consider antifibrinolytic therapy (tranexamic acid) at induction of anesthesia 1
- Continue VWF replacement until adequate hemostasis is achieved 1
Neuraxial Anesthesia
- Minimum VWF activity level of 50 IU/dL is required 2
- For patients with history of severe bleeding, target ≥80 IU/dL 2
- Do not replace VWF if levels are already endogenously within normal range (>50 IU/dL) 2
Pregnancy and Childbirth
- Close monitoring during pregnancy 1
- Target VWF:RCo levels:
- Vaginal delivery: ≥50 IU/dL
- Cesarean section: ≥80 IU/dL 1
Bleeding Episodes
- For mucosal bleeding, hemarthroses, intramuscular hematomas in Type 1: DDAVP is usually effective 6
- For severe bleeding in Type 2B, Type 3, or severe Type 1: VWF-containing factor concentrates 4
- Consider adjunctive antifibrinolytic agents (tranexamic acid) 1, 7
Special Considerations
Acquired von Willebrand Syndrome (AVWS)
- May occur during extracorporeal membrane oxygenation (ECMO) support 2
- Management requires a multidisciplinary approach involving intensivists, hematologists, and perfusionists 2
- Treatment options include minimizing anticoagulation, blood product replacement, desmopressin, and VWF-containing concentrates 2
Monitoring Treatment
- Monitor VWF:RCo, VWF:Ag, and FVIII:C levels to ensure adequate response 6
- For Type 2B, monitor platelet count as thrombocytopenia may worsen with treatment 1
- In cases of bleeding with adequate VWF levels, consider platelet transfusion, though results may be suboptimal as transfused platelets may be aggregated by abnormal VWF 1
Prophylaxis
Long-term prophylaxis with VWF-containing concentrates may benefit patients with recurrent bleeding episodes, particularly those with nose/mouth bleeds and joint bleeds 8. This approach has shown substantial reduction in bleeding episodes and prevention of arthropathy when started before age 5 8.
Family Screening
Screen all first-degree relatives of patients with VWD, including detailed bleeding history and laboratory testing with VWF:Ag, VWF:RCo, and FVIII 1.