Laboratory Tests for Diagnosing Arterial Thromboembolic Disease
For diagnosing arterial thromboembolic disease, a combination of D-dimer testing and appropriate imaging studies is recommended as the primary diagnostic approach, with additional thrombophilia testing in selected cases of unprovoked events, especially in younger patients. 1
Initial Laboratory Evaluation
Basic Laboratory Tests
- Complete blood count (CBC) with platelet count
- Basic coagulation tests:
- Prothrombin time (PT)/International Normalized Ratio (INR)
- Activated partial thromboplastin time (aPTT)
- Fibrinogen level
- D-dimer measurement (highly sensitive assay preferred)
- Comprehensive metabolic panel
- Thyroid function tests 1, 2
D-dimer Testing
- Highly sensitive quantitative D-dimer assays are recommended as first-line testing for patients with low-to-moderate pretest likelihood of disease (Grade 2B)
- Moderate sensitivity qualitative assays are appropriate only for patients with low pretest likelihood (Grade 2C)
- Negative D-dimer with low clinical suspicion effectively excludes thromboembolic disease with 99% negative predictive value 1
- Note: D-dimer has limited utility in patients with conditions that elevate levels (recent surgery, trauma, pregnancy, advanced age) 1, 2
Imaging Studies Based on Clinical Presentation
For Suspected Deep Vein Thrombosis (DVT)
- Initial evaluation with combined modality ultrasound (compression with either Doppler or color Doppler) is recommended over other initial tests 1
- For negative initial ultrasound with high clinical suspicion:
- Further testing with moderate or highly sensitive D-dimer
- Serial ultrasound
- Venographic-based imaging (traditional, CT scan, or MRI) 1
For Suspected Pulmonary Embolism (PE)
- CT pulmonary angiography is recommended for patients with "PE likely" clinical probability or abnormal D-dimer
- Ventilation-perfusion scan is an alternative for patients with contraindications to contrast (renal disease, contrast allergy) 1
For Suspected Cerebral Arterial Thrombosis
- MRI with diffusion-weighted imaging
- CT angiography or MR angiography 1
Additional Testing for Specific Scenarios
Thrombophilia Testing (for unprovoked events, especially in younger patients)
- Factor V Leiden G1691A mutation
- Prothrombin G20210A mutation
- Antithrombin III levels
- Protein C and Protein S levels
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, anti-β2-glycoprotein I) 3, 4, 5
For Suspected Hypercoagulable States
- Homocysteine levels
- Platelet aggregation studies (for suspected platelet hyperreactivity)
- MTHFR C677T polymorphism testing (particularly for arterial events) 2, 4
Special Considerations
Pregnancy
- In pregnant patients with suspected DVT:
- Initial evaluation with proximal compression ultrasound
- For negative initial test: serial proximal ultrasound (day 3 and day 7) or sensitive D-dimer
- For suspected isolated iliac vein thrombosis: Doppler ultrasound of iliac vein, venography, or direct MRI 1
Upper Extremity DVT
- Initial evaluation with combined modality ultrasound
- For negative initial test with high clinical suspicion: D-dimer, serial ultrasound, or venographic-based imaging 1
Common Pitfalls to Avoid
- Relying solely on clinical assessment without objective testing (clinical assessment alone is unreliable) 1
- Using D-dimer as the sole parameter to guide anticoagulation decisions 2
- Failure to consider arterial thrombosis in thrombophilia evaluation (Factor V Leiden may be associated with both venous and arterial thrombosis) 4
- Overlooking the need for thrombophilia testing in young patients with unprovoked arterial events 4
- Not considering the limitations of D-dimer (decreased levels over time since symptom onset, correlation with clot burden, and variable assay characteristics) 2
By following this structured approach to laboratory testing for arterial thromboembolic disease, clinicians can effectively diagnose these conditions while minimizing unnecessary testing and ensuring appropriate management to reduce morbidity and mortality.