What is the initial workup for a patient suspected of having Von Willebrand disease (VWD)?

Initial Workup for Von Willebrand Disease (VWD)

The initial laboratory workup for suspected Von Willebrand Disease should include three specific tests: VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII). 1

Clinical Evaluation

• Begin with a structured bleeding history assessment using specific screening questions to identify patients who would benefit from laboratory testing 2:

  • Initial three screening questions to identify potential bleeding disorders
  • If positive, proceed to nine additional questions focused on VWD symptoms 2
  • Increasing number of positive responses increases likelihood of VWD 2

• Physical examination should focus on:

  • Evidence of bleeding: ecchymoses, hematomas, petechiae 2
  • Signs suggesting other causes: liver disease, splenomegaly, joint/skin laxity, telangiectasia 2
  • Gynecologic examination in females to identify anatomic lesions 2

Laboratory Testing Algorithm

Initial Hemostasis Tests

• Complete blood count (CBC) 2, 1
• Prothrombin time (PT) 2, 1
• Activated partial thromboplastin time (PTT) 2, 1
• These tests do not evaluate for VWD but can suggest other coagulation disorders 2

VWD-Specific Tests

• If mucocutaneous bleeding history is strong, proceed directly to the three core VWD assays 2, 1:
  • VWF antigen (VWF:Ag) - measures quantity of VWF protein 1
  • VWF ristocetin cofactor activity (VWF:RCo) - assesses functional ability of VWF to bind platelets 1
  • Factor VIII coagulant activity (FVIII) - evaluates level of factor VIII 1

Interpretation of Initial Results

• All three tests are necessary to establish diagnosis and suggest VWD type and severity 2
• Abnormal results may include:
  • Low VWF:Ag, VWF:RCo, and FVIII (quantitative defect - Type 1 or 3) 1, 3
  • Discrepant VWF:RCo to VWF:Ag ratio below 0.5-0.7 (qualitative defect - Type 2) 2, 3

Specialized Testing

• If initial VWD testing identifies abnormalities, consider reflexive testing 2:
  • VWF multimer analysis - visualizes distribution of plasma VWF multimers 2, 1
  • Collagen binding assay (VWF:CB) - helps differentiate VWD subtypes 3
  • Ristocetin-induced platelet aggregation (RIPA) - particularly useful for Type 2B VWD 3

Important Considerations

• VWF multimer analysis should NOT be part of initial screening 2, 1

• Bleeding time and platelet function analyzer (PFA-100) tests have conflicting data regarding sensitivity and specificity and are not recommended for routine screening 2, 1

• Patient conditions affecting test results 2:

  • Stress, exercise, inflammation can falsely elevate VWF levels 2
  • ABO blood group affects VWF levels (group O has 25% lower levels) 2
  • Pregnancy or estrogen therapy increases VWF levels 2

• Sample handling considerations 2:

  • Transport blood samples at room temperature 2
  • Separate plasma promptly at room temperature 2
  • Freeze samples at or below -40°C if not tested within 2 hours 2

Common Pitfalls to Avoid

• Relying on a single test for VWD diagnosis - no single test can screen for all forms 1, 4

• Ordering VWF multimer analysis as part of initial screening 2, 1

• Testing during conditions that elevate baseline VWF (pregnancy, inflammation, stress) 2, 1

• Improper sample handling leading to false results 2

• For patients with abnormal initial test results, consultation with a hemostasis specialist is recommended for further evaluation and management 1, 4