What blood work is recommended for diagnosing and managing von Willebrand disease?

Laboratory Evaluation for von Willebrand Disease

The initial laboratory evaluation for diagnosing von Willebrand disease (VWD) should include 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 Testing Algorithm

First-Line Tests:

• Complete Blood Count (CBC) - to evaluate for anemia and platelet count
• Prothrombin Time (PT) - to assess extrinsic pathway
• Activated Partial Thromboplastin Time (aPTT) - may be prolonged in VWD
• VWF Antigen (VWF:Ag) - measures the amount of VWF protein
• VWF Ristocetin Cofactor Activity (VWF:RCo) - measures VWF function
• Factor VIII Coagulant Activity (FVIII) - often reduced in VWD

The initial three VWD-specific tests (VWF:Ag, VWF:RCo, and FVIII) are considered grade B recommendations by the National Heart, Lung, and Blood Institute (NHLBI) guidelines and are essential for establishing both the diagnosis and potential type of VWD 1.

Second-Line Tests (if initial tests are abnormal):

• VWF Multimer Analysis - to determine distribution of VWF multimers
• Ratio of VWF:RCo to VWF:Ag - ratio below 0.5-0.7 suggests qualitative VWD
• Collagen Binding Assay
• Ristocetin-Induced Platelet Aggregation (RIPA)
• FVIII Binding Capacity of VWF
• Platelet VWF Studies
• DNA Sequencing of VWF Gene (in selected cases)

Critical Sample Collection Considerations

Proper sample collection and handling are crucial for accurate VWD testing:

1. Atraumatic Blood Draw - To minimize tissue factor exposure and activation of clotting factors 1
2. Room Temperature Transport - Blood samples must be transported at room temperature to prevent cryoprecipitation 1, 2
3. Prompt Processing - Plasma should be separated from blood cells quickly at room temperature 1
4. Thorough Centrifugation - To remove platelets completely 1
5. Proper Storage - If not tested within 2 hours, samples should be frozen at or below -40°C 1

Factors Affecting Test Results

Several factors can influence VWF levels and must be considered when interpreting results:

• ABO Blood Type - Type O individuals have VWF levels approximately 25% lower than other blood types 1, 2
• Stress Level - Anxiety, crying in children, or recent exercise can falsely elevate VWF levels 1
• Inflammatory Conditions - Acute or chronic inflammation can elevate VWF levels 1
• Hormonal Status - Pregnancy or estrogen/oral contraceptives can increase VWF levels 1
• Ethnicity - African-Americans typically have higher VWF levels than Caucasians 1

Diagnostic Interpretation

The interpretation of test results should consider:

1. Type 1 VWD (70% of cases): Partial quantitative deficiency with proportional decreases in VWF:Ag and VWF:RCo 3, 4
2. Type 2 VWD (20-30% of cases): Qualitative defects with disproportionate reduction in VWF function
   • Type 2A: Decreased high-molecular-weight multimers
   • Type 2B: Increased affinity for platelets
   • Type 2M: Decreased platelet-dependent function
   • Type 2N: Decreased FVIII binding capacity
3. Type 3 VWD (rare): Complete absence of VWF 4, 5

Common Pitfalls to Avoid

• Relying on Bleeding Time or PFA-100 - These tests lack sensitivity and specificity for VWD and are not recommended for routine screening 1
• Testing During Acute Phase Reactions - Can mask underlying bleeding disorders 2
• Ignoring ABO Blood Type - Failure to consider blood type can lead to misinterpretation of results 2
• Improper Sample Handling - Can lead to falsely abnormal results 1, 2
• Single Testing - VWD testing should be repeated if initial results are borderline or inconclusive 1

By following this systematic approach to laboratory testing for VWD, clinicians can accurately diagnose this common bleeding disorder and appropriately classify its type, which is essential for proper management and treatment.