What lab tests are used to diagnose and manage von Willebrand's disease?

Laboratory Tests for von Willebrand Disease (VWD)

The initial laboratory evaluation for von Willebrand disease should include a complete blood count (CBC), prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor antigen (VWF:Ag), von Willebrand factor ristocetin cofactor activity (VWF:RCo), and factor VIII coagulant activity (FVIII). 1, 2

Initial Laboratory Evaluation

First-Line Tests

• Complete Blood Count (CBC) - To evaluate for thrombocytopenia
• Prothrombin Time (PT) - To assess extrinsic pathway
• Activated Partial Thromboplastin Time (aPTT) - May be prolonged in VWD, especially with low FVIII
• VWF Antigen (VWF:Ag) - Measures the quantity of VWF protein
• VWF Ristocetin Cofactor Activity (VWF:RCo) - Assesses VWF function
• Factor VIII Coagulant Activity (FVIII) - Often decreased in VWD due to reduced VWF carrier function

These three VWD-specific tests (VWF:Ag, VWF:RCo, and FVIII) are essential for initial evaluation and can help establish both the diagnosis and suggest the type and severity of VWD if present 1.

Important Diagnostic Ratios

• VWF:RCo/VWF:Ag ratio - A ratio below 0.5-0.7 suggests qualitative VWF defects (Type 2 VWD) 1, 2

Specialized Testing for VWD Classification

If initial testing suggests VWD or if there is strong clinical suspicion despite normal initial tests, additional specialized tests may be required:

VWF Multimer Analysis

• Not recommended for initial screening
• Should only be performed when initial VWD testing identifies abnormal results
• Visualizes the distribution of plasma VWF multimers
• Helps determine VWD subtype 1

Additional Specialized Tests

• VWF Collagen Binding Assay (VWF:CB) - Provides additional functional assessment of VWF 3
• Ristocetin-Induced Platelet Aggregation (RIPA) - Particularly useful for diagnosing Type 2B VWD 4
• VWF:FVIII Binding Capacity - Helps identify Type 2N VWD 3, 4

Pre-Analytical Considerations

Several factors can affect test results and should be considered:

• Patient factors that can elevate VWF and FVIII levels:

  • Stress
  • Exercise
  • Inflammation
  • Pregnancy
  • Estrogen use
  • ABO blood type (type O has lower levels)
  • Ethnicity 2

• Medication interference:

  • Discontinue medications affecting platelet function 7-10 days before testing 2

Interpretation and Classification

Based on laboratory findings, VWD is classified into three main types:

1. Type 1 (~75% of cases)

   • Partial quantitative deficiency
   • Proportional decrease in VWF:Ag and VWF:RCo
   • Normal VWF:RCo/VWF:Ag ratio

2. Type 2

   • Qualitative deficiency
   • Abnormal VWF:RCo/VWF:Ag ratio (<0.5-0.7)
   • Subtypes include 2A, 2B, 2M, and 2N, distinguished by multimer analysis and specialized tests

3. Type 3 (rare)

   • Complete or near-complete absence of VWF
   • Very low VWF:Ag, VWF:RCo, and FVIII 2

Common Pitfalls and Caveats

1. Normal PT and aPTT do not exclude VWD - VWD often presents with normal PT and aPTT, highlighting the importance of specific VWF testing 2

2. Bleeding time or PFA-100 limitations - These tests have conflicting data regarding sensitivity and specificity for VWD and are not recommended as routine screening tests 1

3. Repeat testing may be necessary - Up to 60-70% of patients with mild-moderate bleeding may have a bleeding disorder of unknown cause despite normal initial testing 2

4. Consultation with hematology specialists is recommended when:

   • Initial testing is abnormal
   • High clinical suspicion exists despite normal testing
   • Test results are borderline or difficult to interpret 2

5. Treatment decisions depend on accurate diagnosis and classification:

   • Desmopressin (DDAVP) is first-line for most Type 1 and some Type 2 VWD
   • VWF-containing concentrates are used for Type 3, severe Type 1, and most Type 2 variants 2, 5

By following this systematic laboratory approach, clinicians can effectively diagnose, classify, and manage patients with von Willebrand disease.