What is the management of Von Willebrand disease?

Management of Von Willebrand Disease

Desmopressin (0.3 μg/kg) is the first-line treatment for patients with Type 1 von Willebrand disease and some Type 2 variants, while VWF-containing concentrates are recommended for Type 3 and severe forms of Types 1 and 2 that are unresponsive to desmopressin. 1

Diagnosis and Classification

Before initiating treatment, proper diagnosis and classification of VWD is essential:

Initial Laboratory Evaluation

• Complete blood count (CBC)
• Prothrombin time (PT) and activated partial thromboplastin time (PTT)
• VWF antigen (VWF:Ag)
• VWF ristocetin cofactor activity (VWF:RCo)
• Factor VIII coagulant activity (FVIII) 1

VWD Classification

• Type 1 (75% of cases): Partial quantitative deficiency of VWF
• Type 2 (qualitative deficiency) with subtypes:
  • 2A: Decreased high-molecular-weight multimers
  • 2B: Increased affinity for platelets
  • 2M: Decreased platelet-dependent function
  • 2N: Decreased FVIII binding
• Type 3 (rare): Complete absence of VWF 1, 2

Treatment Algorithm

1. For Type 1 VWD (VWF levels >5%)

• First-line therapy: Desmopressin 0.3 μg/kg IV 1, 3
  • Administer 30 minutes before scheduled procedures
  • Can be used for spontaneous bleeding episodes
  • Test dose recommended at diagnosis to establish individual response pattern 4
  • Effective for most minor bleeding and surgical prophylaxis
  • May be repeated at 12-24 hour intervals, but tachyphylaxis can occur after 3-5 doses 1

2. For Type 2 VWD

• Type 2A, 2M: Generally unresponsive to desmopressin; use VWF concentrates 5, 6
• Type 2B: Desmopressin contraindicated due to risk of transient thrombocytopenia 4
• Type 2N: May respond to desmopressin if FVIII levels are adequate 6

3. For Type 3 VWD (VWF levels <5%)

• First-line therapy: VWF/FVIII concentrates 5, 6
• Desmopressin is ineffective 1, 3

4. For Acquired von Willebrand Syndrome (AVWS)

• Treat underlying condition when possible
• Desmopressin may be effective in some cases
• VWF concentrates for refractory bleeding 1

Adjunctive Therapies

• Antifibrinolytic agents (e.g., tranexamic acid)
• Topical hemostatic agents
• Hormonal therapies for menorrhagia 2

Special Considerations

Surgery and Invasive Procedures

• Administer desmopressin 30 minutes before scheduled procedures in responsive patients
• For major surgery in Type 3 or severe Types 1 and 2, use VWF/FVIII concentrates 3, 6
• Monitor VWF:RCo, VWF:Ag, and FVIII levels to ensure adequate hemostasis 3

Pregnancy and Childbirth

• VWF levels typically increase during pregnancy but fall rapidly after delivery
• Prophylactic treatment may be needed for delivery, particularly in Types 2 and 3 6

Pediatric Patients

• Same principles apply as for adults
• Careful dosing based on weight is essential 7

Pitfalls and Caveats

1. Desmopressin limitations:

   • Ineffective in Type 3 VWD and severe forms of Types 1 and 2
   • Risk of tachyphylaxis with repeated doses
   • Potential hyponatremia with fluid retention; monitor fluid intake 1

2. Diagnostic challenges:

   • VWF levels fluctuate with stress, exercise, pregnancy, and other conditions
   • Blood type affects VWF levels (lower in type O)
   • Repeat testing may be necessary for accurate diagnosis 1, 2

3. Treatment in resource-limited settings:

   • Fresh frozen plasma and cryoprecipitate are viable options when VWF concentrates are unavailable 7

4. Monitoring:

   • For major procedures, monitor VWF:RCo, VWF:Ag, and FVIII levels to ensure adequate hemostasis
   • Target levels of >50 IU/dL for minor procedures and >100 IU/dL for major surgery 3

By following this structured approach to VWD management based on disease type and severity, clinicians can effectively control bleeding and prevent complications in patients with this common inherited bleeding disorder.