Von Willebrand Disease: Diagnosis and Management
Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting up to 1% of the general population, characterized by deficiencies or dysfunction of von Willebrand factor (VWF) resulting in excessive mucocutaneous bleeding. 1, 2
Types and Classification
VWD is classified into several types based on the nature of the VWF defect:
- Type 1: Partial quantitative deficiency of VWF (most common)
- Type 2: Qualitative defects in VWF function
- Type 2A: Decreased VWF-dependent platelet adhesion with selective deficiency of high-molecular-weight multimers
- Type 2B: Increased affinity for platelet glycoprotein Ib
- Type 2M: Decreased VWF-dependent platelet adhesion without selective deficiency of high-molecular-weight multimers
- Type 2N: Markedly decreased binding affinity for factor VIII
- Type 3: Complete or near-complete absence of VWF (most severe)
- Platelet-type VWD: Enhanced binding of normal VWF to platelets 1
Clinical Manifestations
The hallmark of VWD is mucocutaneous bleeding, with severity varying based on VWD type and degree of VWF deficiency:
- Epistaxis (nosebleeds)
- Easy bruising
- Prolonged bleeding from minor wounds
- Heavy menstrual bleeding (menorrhagia)
- Postpartum hemorrhage
- Bleeding after dental procedures or surgery
- Gastrointestinal bleeding (less common)
- Joint bleeding/hemarthrosis (rare, except in Type 3) 1, 2
Diagnostic Approach
Diagnosis requires specialized laboratory testing:
Initial laboratory evaluation:
- Complete blood count
- Coagulation profile (PT, aPTT)
- VWF antigen (VWF:Ag)
- VWF activity (VWF:RCo)
- Factor VIII levels 1
Key diagnostic findings:
- PT is typically normal in VWD
- aPTT may be prolonged in severe cases due to decreased factor VIII
- VWF:RCo/VWF:Ag ratio <0.7 suggests qualitative defects
- VWF multimer analysis shows characteristic patterns based on VWD type 1
Additional testing:
Treatment Approaches
Treatment is tailored to VWD type, severity, and clinical situation:
1. Desmopressin (DDAVP)
- First-line therapy for Type 1 VWD
- Stimulates release of VWF from endothelial cells
- Not effective in Type 3 and some Type 2 variants 1, 4
2. VWF/Factor VIII Concentrates
- Indicated for:
- Type 3 VWD
- Most Type 2 variants
- Type 1 patients unresponsive to desmopressin
- Severe bleeding episodes
- Typical dosing: 40 IU/kg of VWF-containing concentrates
- Target VWF activity level ≥50 IU/dL for acute bleeding 1
3. Adjunctive Therapies
- Antifibrinolytic agents (e.g., tranexamic acid)
- Hormonal therapy for menorrhagia
- Topical hemostatic agents 1, 4, 2
4. Long-term Prophylaxis
- Recommended for patients with severe bleeding phenotypes
- Typical dosing: 24 units FVIII/kg body weight, 1-3 times weekly 1
Special Considerations
Women with VWD
- Heavy menstrual bleeding is a common symptom
- Management options include:
- Hormonal contraceptives
- Tranexamic acid
- VWF replacement therapy
- Pregnancy typically increases VWF levels, but postpartum hemorrhage risk remains high
- Interdisciplinary management during childbirth is essential 1, 3, 5
Acquired von Willebrand Syndrome (AVWS)
- Can occur in association with:
- Myeloproliferative disorders
- Continuous-flow mechanical circulatory support devices
- Severe aortic stenosis
- Treatment includes addressing underlying condition and VWF replacement as needed 1
Clinical Pitfalls and Caveats
- VWD is frequently underdiagnosed, especially in women with menorrhagia (5-20% of women with menorrhagia have undiagnosed VWD)
- Bruising in children with VWD must be carefully distinguished from child abuse
- VWF levels fluctuate with stress, exercise, pregnancy, and hormonal changes, which can complicate diagnosis
- Monitoring for thrombotic risk is necessary during treatment with VWF-containing concentrates 1, 5