What is the management approach for Von Willebrand disease?

Management of Von Willebrand Disease

The management of Von Willebrand Disease (VWD) should primarily focus on desmopressin for type 1 VWD and VWF-containing factor concentrates for types 2 and 3 VWD, with treatment targets of VWF:RCo levels ≥50 IU/dL for minor procedures and ≥80-100 IU/dL for major procedures. 1, 2

Diagnosis and Classification

Before initiating treatment, proper classification of VWD is essential:

• Type 1 VWD (80% of cases): Partial quantitative deficiency of VWF
• Type 2 VWD: Qualitative defects in VWF
  • Type 2A: Decreased platelet-dependent function with loss of high and intermediate MW multimers
  • Type 2B: Enhanced binding to platelets with loss of high MW multimers
  • Type 2M: Decreased platelet-dependent function without loss of high MW multimers
  • Type 2N: Decreased binding affinity for FVIII
• Type 3 VWD: Complete deficiency of VWF

Laboratory evaluation should include:

• Complete blood count with platelet count
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT)
• 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

1. Desmopressin (DDAVP)

First-line therapy for Type 1 VWD with factor VIII and VWF levels >10 IU/dL who demonstrate responsiveness to a test dose 2, 3:

• Dosage: 0.3 μg/kg intravenously, diluted in 50 ml saline and infused over 30 minutes 4
• Timing: Administer 30 minutes prior to scheduled procedures 2
• Mechanism: Releases VWF from endothelial cell Weibel-Palade bodies
• Monitoring: Check VWF:RCo, VWF:Ag, and FVIII:C levels to ensure adequate response
• Limitations:
  • Tachyphylaxis may occur after 3-5 doses due to depletion of VWF stores 4
  • Not effective in Type 3 VWD and most Type 2 variants 3, 5
  • Contraindicated in Type 2B VWD as it may worsen thrombocytopenia 1

2. VWF-Containing Factor Concentrates

First-line therapy for:

• Type 2 and Type 3 VWD
• Type 1 patients unresponsive to desmopressin
• Major surgical procedures requiring sustained hemostasis 1, 3

Target levels:

• ≥50 IU/dL for minor procedures or bleeding
• ≥80-100 IU/dL for major procedures 4, 1

Administration:

• Maintain target levels for the duration of bleeding risk
• For surgical procedures, continue therapy until adequate wound healing 1

3. Adjunctive Therapies

• Antifibrinolytic agents (tranexamic acid):

  • Useful for mucosal bleeding
  • Can be used in conjunction with desmopressin or factor concentrates
  • Consider at induction of anesthesia for surgical procedures 1

• Hormonal therapies for menorrhagia:

  • Combined oral contraceptives
  • Levonorgestrel-releasing intrauterine device

Special Clinical Scenarios

Pregnancy Management

• VWF levels typically increase during pregnancy, especially in the third trimester
• Target VWF:RCo ≥50 IU/dL for vaginal delivery and ≥80 IU/dL for cesarean section 1
• Monitor closely during postpartum period as VWF levels rapidly decrease after delivery

Neuraxial Anesthesia

• Ensure VWF activity level is ≥50 IU/dL before neuraxial procedures 4
• For patients with history of severe bleeding, target VWF activity level ≥80 IU/dL 4
• For Type 2B VWD, additional monitoring of platelet count is necessary 4, 1

Management of Acute Bleeding

1. Assess severity and location of bleeding
2. For mild-moderate Type 1 VWD:
   • Administer desmopressin if previously responsive
   • Consider antifibrinolytic agents for mucosal bleeding
3. For Type 2, Type 3, or severe Type 1 VWD:
   • Administer VWF-containing factor concentrates
   • Target VWF:RCo levels based on bleeding severity
4. For Type 2B VWD with bleeding:
   • Use VWF-containing factor concentrates
   • Monitor platelet count
   • Consider platelet transfusion if severe thrombocytopenia is present 1

Common Pitfalls and Considerations

1. Misdiagnosis risk: VWD is often misdiagnosed, overdiagnosed, or underdiagnosed due to variable bleeding symptoms and external modifiers 6

2. Desmopressin limitations:

   • Not effective in Type 3 VWD
   • Contraindicated in Type 2B VWD
   • May cause fluid retention, hyponatremia, or tachyphylaxis with repeated doses 4

3. VWF concentrate selection:

   • Choose products containing intact VWF multimers
   • Virally attenuated commercial concentrates are preferred over cryoprecipitate 7

4. Monitoring considerations:

   • Regular assessment of VWF:RCo, VWF:Ag, and FVIII:C levels during treatment
   • For Type 2B VWD, monitor platelet count closely 1

5. Family screening:

   • Screen first-degree relatives due to the hereditary nature of VWD 1

By following this algorithmic approach and understanding the specific characteristics of each VWD subtype, clinicians can effectively manage bleeding episodes and prevent complications in patients with VWD.