What is the management approach for von Willebrand disease?

Management of von Willebrand Disease

The management of von Willebrand disease (VWD) should be tailored based on disease type and severity, with desmopressin (DDAVP) as first-line therapy for mild to moderate Type 1 VWD and VWF-containing factor concentrates for Type 2B, Type 3, and severe forms of Type 1 and 2 VWD. 1

Diagnosis and Classification

Proper management begins with accurate diagnosis and classification:

• Laboratory testing for VWD should include:

  • VWF antigen (VWF:Ag)
  • VWF ristocetin cofactor activity (VWF:RCo)
  • Factor VIII coagulant activity (FVIII:C) 1

• Important diagnostic considerations:

  • VWD is not reliably detected by PT/aPTT screening alone
  • Normal PT and aPTT may still be present in VWD patients who can experience significant bleeding
  • A bleeding assessment tool (BAT) should be used during clinical evaluation 1

• VWD classification impacts treatment selection:

  • Type 1: Quantitative deficiency of VWF
  • Type 2: Qualitative defects (subtypes 2A, 2B, 2M, 2N)
  • Type 3: Complete deficiency of VWF 1

Treatment Approach

First-Line Therapy: Desmopressin (DDAVP)

• For mild to moderate Type 1 VWD:

  • Dosage: 0.3 μg/kg IV diluted in 50 ml saline infused over 30 minutes
  • Can be repeated at 12-24 hour intervals
  • Tachyphylaxis may occur after 3-5 doses 1, 2
  • FDA approved for VWD Type I with factor VIII levels >5% 2

• Response monitoring:

  • Check bleeding time, factor VIII activity, ristocetin cofactor activity, and VWF antigen during administration 2
  • A minimum VWF activity level of 50 IU/dL is required for adequate hemostasis
  • For severe bleeding history, target VWF activity level of ≥80 IU/dL 1

Second-Line Therapy: VWF-Containing Factor Concentrates

• Indicated for:

  • Type 2B VWD
  • Type 3 VWD
  • Severe forms of Type 1 and 2 VWD
  • Patients unresponsive to desmopressin 1

• Target levels:

  • ≥80-100 IU/dL for major procedures
  • VWF replacement not necessary if levels are already >50 IU/dL 1

Special Clinical Situations

Surgical Management

• For patients undergoing major procedures:
  • VWF-containing factor concentrates are the preferred choice for Type 2B VWD
  • Have platelets, cryoprecipitate, and FFP readily available 1

Pregnancy and Delivery

• Close monitoring during pregnancy
• Target VWF:RCo levels:
  • ≥50 IU/dL for vaginal delivery
  • ≥80 IU/dL for cesarean section 1

Family Screening

• Screen all first-degree relatives due to hereditary nature
• Include detailed bleeding history and laboratory testing with VWF:Ag, VWF:RCo, and FVIII 1

Important Considerations and Pitfalls

• Desmopressin limitations:

  • Not effective for severe Type 1, most Type 2, and all Type 3 VWD patients
  • Contraindicated in Type 2B (can worsen thrombocytopenia) 1
  • Not indicated when factor VIII levels are ≤5% or when abnormal molecular forms of factor VIII antigen are present 2

• Monitoring considerations:

  • Patients least likely to respond to desmopressin are those with severe homozygous VWD with factor VIII and VWF antigen levels <1% 2
  • Response to treatment is variable depending on molecular defect 2

• Treatment selection pitfalls:

  • Failure to recognize desmopressin non-responders before procedures
  • Inadequate dosing for target VWF activity levels
  • Not accounting for tachyphylaxis with repeated desmopressin doses 1

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