What initial laboratory tests should be ordered for a patient with a suspected bleeding disorder?

Initial Laboratory Tests for Suspected Bleeding Disorders

For patients with suspected bleeding disorders, the initial laboratory evaluation 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

First-Line Laboratory Tests

The initial laboratory evaluation should include:

1. Basic Coagulation Tests:

   • Complete Blood Count (CBC) with platelet count 2, 1
   • Prothrombin Time (PT) 2, 1
   • Activated Partial Thromboplastin Time (aPTT) 2, 1

2. Von Willebrand Disease (VWD) Tests:

   • VWF antigen (VWF:Ag) 2, 1
   • VWF ristocetin cofactor activity (VWF:RCo) 2, 1
   • Factor VIII coagulant activity (FVIII) 2, 1

Interpretation of Initial Tests

• CBC: Evaluates for thrombocytopenia or other hematologic abnormalities
• PT: Assesses the extrinsic and common pathways (factors II, V, VII, X, fibrinogen)
• aPTT: Evaluates the intrinsic and common pathways (factors II, V, VIII, IX, X, XI, XII, fibrinogen)
• VWF:Ag, VWF:RCo, FVIII: These three tests are recommended for initial VWD evaluation and can help establish diagnosis and suggest the type and severity if VWD is present 2

Important Considerations for Testing

• Proper sample collection is critical:

  • Atraumatic blood draw to minimize tissue factor exposure
  • Transport samples at room temperature
  • Separate plasma from blood cells quickly
  • If not tested within 2 hours, freeze samples at or below -40°C 1

• Patient factors that may affect results:

  • Stress, exercise, inflammation, pregnancy, or estrogen use can elevate VWF and FVIII levels
  • ABO blood type (Type O individuals have ~25% lower VWF levels)
  • Ethnicity (African-Americans have higher baseline VWF levels) 1
  • Medications affecting platelet function should be discontinued 7-10 days before testing 1

Follow-Up Testing Based on Initial Results

If initial tests are abnormal or clinical suspicion remains high despite normal initial tests:

• Abnormal VWF tests: Consider VWF multimer analysis if VWF:RCo/VWF:Ag ratio is abnormally low (below 0.5-0.7) 2

• Normal first-line tests with high clinical suspicion: Consider second-line tests:

  • Light Transmission Aggregometry (LTA) with agonists
  • Platelet Function Analyzer (PFA-100/200)
  • Platelet flow cytometry 1

Common Pitfalls to Avoid

1. Relying on bleeding time or PFA-100 alone for screening - These tests lack sensitivity and specificity for VWD 1

2. Single testing - VWD testing should be repeated if initial results are borderline or inconclusive 1

3. Ignoring patient context - Laboratory results must be interpreted in the context of the patient's bleeding history 1

4. Poor sample handling - Improper collection or handling can lead to false results 1

5. Not considering physiologic factors - Stress, pregnancy, or medications can mask underlying disorders 1

The diagnostic approach should be guided by both laboratory findings and clinical presentation, with recognition that up to 60-70% of patients investigated for mild-moderate bleeding disorders may have a bleeding disorder of unknown cause even after initial testing 1.