What labs are used to diagnose clotting disorders or pulmonary embolism (PE)?

Laboratory Tests for Diagnosing Clotting Disorders and Pulmonary Embolism

D-dimer measurement is the primary initial laboratory test for diagnosing pulmonary embolism in patients with low to intermediate clinical probability, while patients with high clinical probability should proceed directly to imaging studies. 1

Clinical Assessment First

Before ordering laboratory tests, assess the clinical probability of PE using:

• Validated clinical prediction rules (Wells score or Geneva score)
• Pulmonary Embolism Rule-Out Criteria (PERC) for low-risk patients 1, 2

Laboratory Tests for PE Diagnosis

First-Line Laboratory Test

• D-dimer:
  • High sensitivity test for ruling out PE in low to intermediate risk patients
  • Normal D-dimer (<500 ng/mL) in low-risk patients has >99% negative predictive value 1, 3
  • Age-adjusted D-dimer thresholds should be used for patients >50 years (age × 10 ng/mL) 1

Important Considerations for D-dimer Testing

• Do not use D-dimer in high clinical probability patients due to low negative predictive value 1
• D-dimer specificity decreases with age, cancer, hospitalization, and pregnancy 1
• Highly sensitive ELISA D-dimer assays are preferred over latex agglutination tests 1

Laboratory Tests for Clotting Disorders

Routine Coagulation Tests

• Prothrombin Time (PT)/International Normalized Ratio (INR):

  • Evaluates extrinsic and common coagulation pathways
  • Abnormal in vitamin K deficiency, liver disease, and factor VII deficiency 4

• Activated Partial Thromboplastin Time (aPTT):

  • Evaluates intrinsic and common coagulation pathways
  • Used for monitoring unfractionated heparin therapy 5, 4

Additional Tests for Hypercoagulable States

• Complete Blood Count (CBC):

  • Platelet count may decrease in PE compared to baseline 6
  • Elevated hematocrit may indicate polycythemia, a risk factor for thrombosis

• Thrombophilia Testing (consider in selected cases):

  • Factor V Leiden mutation
  • Prothrombin gene mutation
  • Protein C, S, and antithrombin III deficiency
  • Antiphospholipid antibodies
  • Homocysteine levels

Diagnostic Algorithm

1. Low Clinical Probability:

   • If PERC negative: No further testing needed 1, 2
   • If PERC positive: Order D-dimer test
     • If D-dimer negative: PE excluded
     • If D-dimer positive: Proceed to imaging (CTPA)

2. Intermediate Clinical Probability:

   • Order D-dimer test
     • If D-dimer negative: PE excluded
     • If D-dimer positive: Proceed to imaging (CTPA) 1

3. High Clinical Probability:

   • Proceed directly to imaging (CTPA) without D-dimer testing 1
   • Consider lower limb compression ultrasonography if CTPA contraindicated

Common Pitfalls to Avoid

• Using D-dimer in high-probability patients (high false negative rate) 1
• Relying on non-ELISA D-dimer assays (lower sensitivity) 1
• Failing to use age-adjusted D-dimer cutoffs in older patients 1
• Ordering D-dimer in hospitalized patients with low specificity due to comorbidities 1
• Interpreting isolated abnormal coagulation tests without clinical context 4

Special Considerations

• In patients with shock or hypotension, bedside echocardiography may be the initial test of choice before laboratory testing 1
• For monitoring unfractionated heparin therapy, aPTT should be checked regularly, though many patients fail to achieve therapeutic levels within 24-48 hours 5
• Consider alternative imaging (V/Q scan) in patients with contraindications to CTPA 1

Remember that while laboratory tests are valuable, the diagnosis of PE ultimately requires integration with clinical assessment and appropriate imaging studies.