What is the diagnostic approach and management for acquired von Willebrand disease?

Diagnostic Approach and Management for Acquired von Willebrand Disease

The diagnosis of acquired von Willebrand disease (AVWS) requires comprehensive laboratory testing including VWF antigen (VWF:Ag), VWF activity assays (VWF:RCo and VWF:CB), factor VIII levels, and VWF multimer analysis, with treatment focused on addressing the underlying disorder while managing bleeding risk with desmopressin or VWF-containing concentrates. 1, 2

Diagnostic Algorithm

Initial Evaluation

• Clinical Assessment:

  • Evaluate for new-onset bleeding symptoms without prior personal/family history
  • Screen for AVWS-associated conditions:
    • Lymphoproliferative disorders
    • Myeloproliferative disorders
    • Cardiovascular conditions (especially aortic stenosis)
    • Autoimmune diseases
    • Certain malignancies

• Initial Laboratory Tests 3, 1:

  • Complete blood count with platelet count
  • Prothrombin time (PT)
  • Activated partial thromboplastin time (aPTT)
  • Fibrinogen (optional)
  • Thrombin time (optional)

Specific VWD Testing

• Core VWF Panel 1:

  • 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)

• Advanced Testing 3, 1, 2:

  • VWF multimer analysis (crucial for AVWS diagnosis - often shows loss of high molecular weight multimers)
  • VWF collagen binding assay (VWF:CB)
  • Ristocetin-induced platelet aggregation (RIPA)
  • Tests for VWF inhibitors/autoantibodies

Diagnostic Pitfalls

• AVWS should be considered in all patients with new-onset bleeding and laboratory findings suggesting VWD, particularly with an AVWS-associated disorder 2
• Repeat testing may be necessary as VWF is an acute phase reactant with levels that can fluctuate 1
• Bleeding time and platelet function analyzer (PFA-100) tests have conflicting data regarding sensitivity/specificity and are not recommended as routine screening tests 3

Management Strategy

Treatment of Underlying Condition

• Primary Approach: Treating the underlying disorder should always be considered as it can lead to remission of AVWS 2
  • Immunosuppressants for autoimmune disorders
  • Surgery for structural cardiovascular issues
  • Chemotherapy for lymphoproliferative/myeloproliferative disorders

Acute Bleeding Management

• First-line therapy 4, 2, 5:

  • Desmopressin (DDAVP):
    • Effective in many AVWS cases
    • Dosing: 0.3 μg/kg IV
    • Monitor response with VWF:RCo and FVIII:C levels
    • Use with caution in patients with cardiovascular disease or thrombotic risk

• Second-line options 2, 5:

  • VWF-containing factor VIII concentrates:
    • For patients unresponsive to desmopressin
    • For major bleeding episodes or surgical procedures
    • Target VWF:RCo levels:
      • Minor procedures: ≥50 IU/dL
      • Major procedures: ≥80-100 IU/dL

• Adjunctive therapies 1, 2:

  • Tranexamic acid: Useful for mucosal bleeding
  • High-dose intravenous immunoglobulin: May be effective in autoantibody-mediated AVWS

Perioperative Management

• AVWS testing is recommended prior to surgery with high bleeding risk in any patient with an AVWS-associated disorder 2
• Have blood products (FFP, platelets, cryoprecipitate) readily available 1
• Consider antifibrinolytic therapy at induction of anesthesia 1
• Regular assessment of coagulation parameters and close monitoring for bleeding postoperatively 1

Special Considerations

Thrombotic Risk

• Many underlying conditions associated with AVWS (e.g., myeloproliferative disorders) also carry thrombotic risk
• Desmopressin should be used with caution in patients with coronary artery disease or hypertension 4
• There have been rare reports of thrombotic events following desmopressin administration 4

Monitoring Response

• Laboratory monitoring should include VWF:RCo, VWF:Ag, and FVIII:C levels 3, 1
• Regular hematology follow-up is recommended to monitor bleeding symptoms and periodic VWF testing 1

AVWS remains a diagnostic challenge due to its heterogeneity and association with various underlying disorders. A systematic approach to diagnosis and individualized treatment strategy based on the underlying pathophysiology is essential for optimal management.