Non-Invasive Laboratory Investigations for Critical Limb Ischemia
In patients with critical limb ischemia, obtain ankle or toe pressure measurements as the essential first-line non-invasive test, followed by duplex ultrasound, CTA, or MRA when revascularization is being considered. 1
Essential Laboratory Tests
The ACC/AHA guidelines specify a comprehensive panel of hematologic and biochemical tests that must be obtained in all CLI patients 1:
- Complete blood count to assess for anemia and infection 1
- Platelet count to evaluate thrombotic risk 1
- Fasting blood glucose and hemoglobin A1c to identify and quantify diabetes 1
- Creatinine to assess renal function before contrast studies 1
- Fasting lipid profile for cardiovascular risk stratification 1
- Urinalysis specifically checking for glycosuria and proteinuria 1
- Resting electrocardiogram to evaluate cardiac status 1
Hemodynamic Assessment: The Critical First Step
Ankle-Brachial Index (ABI)
The resting ABI with or without segmental pressures and waveforms is the recommended initial diagnostic test to establish PAD diagnosis 1:
- Report results as: abnormal (≤0.90), borderline (0.91-0.99), normal (1.00-1.40), or noncompressible (>1.40) 1
- Measure blood pressure in both arms to identify the highest systolic pressure for accurate ABI calculation 1
Toe-Brachial Index (TBI): When ABI Fails
TBI should be measured when ABI is >1.40 (noncompressible arteries), which commonly occurs in diabetic patients and those with chronic kidney disease 1, 2:
- TBI is particularly valuable in CLI patients with nonhealing wounds or gangrene when ABI is unreliable 1
- Research demonstrates that post-exercise TBI has superior discriminant ability for severe limb ischemia compared to resting measurements 3
- A TBI ≤0.70 in the setting of noncompressible arteries (ABI >1.40) confirms CLI 1
Additional Perfusion Measures
In CLI patients with normal or borderline ABI but nonhealing wounds or gangrene, obtain TBI with waveforms, transcutaneous oxygen pressure (TcPO2), or skin perfusion pressure (SPP) 1:
- TcPO2 measurement provides valuable information when rest pain and foot ulcerations are present 4
- These measures help evaluate local tissue perfusion in established CLI 1
Anatomic Imaging: Planning Revascularization
Non-Invasive Angiography
Duplex ultrasound, CTA, or MRA of the lower extremities is useful to diagnose anatomic location and severity of stenosis when revascularization is considered 1:
- Duplex ultrasound is the most important non-invasive tool, combining hemodynamic evaluation with imaging 4
- Both CTA and MRA compare favorably with contrast angiography and can guide clinical management effectively 4, 5
- The choice between modalities depends on local availability, expertise, and patient factors (renal function for CTA, pacemakers for MRA) 4, 5
Critical Caveat
Invasive and non-invasive angiography should NOT be performed for anatomic assessment in asymptomatic PAD patients 1. This is a Class III (Harm) recommendation, as imaging should only guide revascularization decisions in symptomatic patients 1.
Segmental Pressures and Waveform Analysis
Segmental lower extremity blood pressures with Doppler or plethysmographic waveforms (pulse volume recordings) can localize anatomic segments of disease 1:
- These tests identify whether disease is aortoiliac, femoropopliteal, or infrapopliteal 1
- Pulse volume recording parameters, particularly upstroke time and percentage mean artery pressure, can predict CLI progression 6
Cardiovascular Risk Assessment
The ACC/AHA guidelines recommend additional screening in selected high-risk CLI patients 1:
- Duplex scan of carotid arteries should be considered in patients with cerebrovascular symptoms or when carotid revascularization risk is lower than short-term stroke risk 1
- Coronary assessment may be performed in patients with coronary ischemic symptoms, but should not delay CLI management 1
Common Pitfalls to Avoid
- Never rely solely on ABI in diabetic patients or those with chronic kidney disease—arterial calcification causes falsely elevated readings; always obtain TBI in these populations 1, 2
- Do not order anatomic imaging (CTA/MRA/angiography) before establishing hemodynamic severity with ABI or TBI 1
- Avoid attributing symptoms to deconditioning in older adults with vascular risk factors without measuring ABI to exclude PAD 2
- Physical examination findings alone are insufficient—always confirm with objective hemodynamic testing 2