Laboratory Studies
Screening laboratory studies
Several screening laboratory studies are useful for evaluating the possibility of associated systemic risk factors and contributing problems.
Perform a complete blood count (CBC) to screen for hematologic diseases such as thrombocytopenia, thrombocytosis, polycythemia, and leukemia. Obtain a fasting blood glucose level to screen for diabetes. Creatinine and blood urea nitrogen (BUN) determinations help screen for renal insufficiency. A fasting and lipid profile helps screen for hyperlipidemia. Perform a urinalysis to screen for glycosuria or proteinuria.
Perform a coagulation workup to assess the prothrombin time (PT) and the activated partial thromboplastin time (aPTT). In some cases (eg, patients with a personal or family history of thrombotic problems, particularly a history of failed vascular interventions), the workup should include a fibrinogen level, a euglobulin lysis time, a protein C assay, a protein S assay, antiphospholipid antibody titers, and an anticardiolipin antibody assay.
Consider obtaining a serum homocysteine level to screen for hyperhomocysteinemia in patients with an atypical history, early onset, or a family history. This problem, which is associated with both arterial and venous disease, can be treated by dietary supplementation with folate and vitamin B12. However, no conclusive data indicate that such treatment lowers long-term vascular risks.
Consider determining the erythrocyte sedimentation rate (ESR). Although elevation of the ESR is a nonspecific finding, the test screens patients with vascular disease for two potential risk factors that are somewhat difficult to measure directly—namely, hyperfibrinogenemia and hyperviscosity syndromes.
Noninvasive vascular laboratory evaluation
Pulse-volume recording (PVR), or plethysmography, uses pneumatic cuffs encircling the thighs, calves, ankles, feet, and sometimes toes to sense segmental volume changes with each pulse beat. The resulting tracings provide useful information about the hemodynamic effects of the arterial disease at each level.
In patients with severe disease, tracings at the transmetatarsal level may become nearly flat. In patients with mild disease, particularly disease involving the aortoiliac segment, PVR tracings may appear normal at rest and may become abnormal only after the patient walks until symptoms occur. PVR is noninvasive and rapid; therefore, it may be repeated frequently to help assess the overall hemodynamic response to medical or surgical treatment.
A handheld Doppler scanner may be used to assess arterial signals, to localize arteries to facilitate palpation of pulses, or to determine loss of the Doppler signal as a proximal blood pressure cuff is inflated. The latter pressure divided by the upper-extremity systolic pressure is called the ankle-brachial index (ABI) and can help indicate the severity of arterial compromise. [32]
A normal ABI averages 1. An ABI less than 0.9 suggests atherosclerotic disease with a sensitivity of approximately 95% and a specificity of 99%. [5] In general, an ABI below 0.3 suggests a poor chance for healing of distal ischemic ulcerations. Unfortunately, the ABI is often falsely elevated if the underlying arteries are heavily calcified, a finding common in patients with diabetes.
Skin perfusion pressure (SPP) is defined as the pressure at which skin perfusion returns as an inflated blood pressure cuff is slowly deflated. This point can be measured by using washout of a radioisotope, the reappearance of pulsatile flux on photoplethysmography, or the motion of erythrocytes on laser Doppler. An SPP higher than 40 mm Hg correlates with the likelihood of the healing of ischemic wounds. [33]
Duplex scanning can provide images of arterial segments that help localize the extent of disease, and simultaneous Doppler measurement of flow velocity can help estimate the degree of stenosis. Duplex scanning is quite useful in visualizing aneurysms, particularly of the aorta or popliteal segments. Unfortunately, Doppler techniques are not accurate for assessing the hemodynamic consequences of atherosclerotic peripheral arterial disease involving the extremities.
Angiography
Conventional angiography
If surgical treatment is contemplated, angiography is needed to delineate the extent and significance of atherosclerotic disease. (See the image below.) Major risks associated with conventional contrast-injection angiography are related to the puncture and to the use of contrast agents.
Contrast angiogram showing severe atherosclerotic disease in distal superficial femoral artery.
Technique
Typically, a catheter is inserted retrograde via a femoral puncture, and contrast is power-injected into the infrarenal aorta. Films are taken as the contrast is followed down to both feet. In certain cases, as with aortic occlusion, a femoral approach to the aorta may not be possible. In this case, the radiologist may use an alternate entry such as via an axillary artery or even directly into the infrarenal aorta via a translumbar approach.
Puncture-related complications
The arterial catheter is usually passed through a 5-French sheath that is 1.6 mm in diameter. This is a sizable hole in the femoral artery, which may be only 6-10 mm in diameter. After the catheter is removed, gentle pressure must be applied to the puncture site for approximately 30 minutes, and the radiologist must balance the need for hemostasis against the possibility of arterial occlusion.
Risks include hemorrhage, pseudoaneurysm formation, and clotting or dislodgment of an intimal flap, which may acutely occlude the artery at or near the entry site. Current methods of percutaneous closure of the puncture sites have significantly reduced the site complication rates.
Contrast-related risks
Angiographic contrast material is nephrotoxic. The risk of precipitating acute renal failure is highest in patients with underlying renal insufficiency and those with diabetes; patients with both of these risk factors have a 30% rate of acute renal failure following contrast angiography. Hence, an acceptable serum creatinine level must be confirmed prior to elective angiography.
Avoid contrast angiography (if possible) for patients with any significant degree of renal impairment. If contrast angiography is absolutely required despite renal impairment, use a minimal volume of contrast material. In addition, providing adequate hydration prior to, during, and after the procedure is essential. Oral administration of the antioxidant acetylcysteine the night prior to and then just before angiography may be protective of renal function for patients at risk for contrast-induced nephropathy. [34]
Metformin warning
To prevent the possibility of fatal lactic acidosis, patients with diabetes who are taking metformin must not take this medication immediately following contrast angiography. Patients may resume taking the medication when normal renal function is confirmed 1-2 days after contrast exposure.
Alternatives to conventional angiography
Magnetic resonance angiography
Magnetic resonance angiography (MRA) is an alternative for patients who are allergic to iodinated contrast material. However, MRA is not innocuous. Gadolinium chelates, the contrast agents used in MRA, have been linked to three potentially serious side effects in patients with renal insufficiency: acute renal injury, pseudohypocalcemia, and nephrogenic systemic fibrosis. [35]
MRA is contraindicated in patients with implanted hardware, such as a hip prosthesis or pacemaker. The resolution may be inadequate for the vascular surgeon in planning reconstructive procedures, particularly in the smaller infrapopliteal arteries, though MRA technology and contrast agents continue to improve. [36]
Multidetector computed tomographic angiography
Multidetector CT (MDCT) angiography avoids arterial puncture. By using precisely timed intravenous contrast injection, 16- or 64-channel MDCT scanners can generate angiographic images of excellent resolution and at a relatively high acquisition speed. MDCT carries the contrast-related risks described above. [37]
Carbon dioxide angiography
Carbon dioxide angiography is an alternative for patients with renal insufficiency; however, it is not widely available and requires some iodinated contrast material in addition to the carbon dioxide gas in order to provide useful images.
Plain Radiography
Plain radiographs are not routinely obtained in the workup of peripheral arterial occlusive disease. This is because arterial calcification seen on plain radiography is not a specific indicator of severe atherosclerotic disease. Calcification of the arterial media is not diagnostic of atherosclerosis, and even calcification of the arterial intima, which is diagnostic of atherosclerotic disease, does not necessarily imply hemodynamically significant stenosis.
Histologic Findings
Atherosclerotic vessels demonstrate proliferation of smooth-muscle cells in the intima and invasion of the damaged intima by atherosclerotic plaque consisting of necrotic cells, lipids, cholesterol crystals, and connective tissue. These lesions typically occur in an eccentric location with respect to the arterial lumen. Soft thrombus may deposit on ulcerated atherosclerotic plaques.
Staging
Rutherford et al described a classification scheme for lower-extremity chronic limb ischemia (CLI; see Table 1 below). [38] The term chronic limb-threatening ischemia (CLTI) is increasingly preferred to CLI. [6]
Table 1. Staging for Chronic Limb Ischemia (Open Table in a new window)
Rutherford Category |
Fontaine Grade |
Clinical Description |
Objective Criteria |
0 |
0 |
Asymptomatic – No hemodynamically significant disease |
Normal treadmill or reactive hyperemia test |
1 |
|
Mild claudication |
Completes treadmill exercise (5 min at 2 mph on 12% incline) AP* after exercise >50 mm Hg but at least 20 mm Hg lower than resting value |
2 |
I |
Moderate claudication |
Between Rutherford categories 1 and 3 |
3 |
|
Severe claudication |
Cannot complete treadmill exercise and AP after exercise < 50 mm Hg |
4 |
II |
Ischemic rest pain |
Resting AP < 40 mm Hg, flat or barely pulsatile ankle or metatarsal PVR**; TP † < 30 mm Hg |
5 |
III |
Minor tissue loss (nonhealing ulcer, focal gangrene with diffuse pedal ischemia) |
Resting AP < 60 mm Hg, ankle or metatarsal PVR flat or barely pulsatile; TP < 40 mm Hg |
6 |
|
Major tissue loss (extending above transmetatarsal level, functional foot no longer salvageable) |
Same as Rutherford category 5 |
*AP = Ankle pressure. **PVR = Pulse-volume recording. † TP = Toe pressure. |
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The Society for Vascular Surgery (SVS) subsequently proposed a lower-extremity threatened limb classification system based on grading three major factors—wound, ischemia, and foot infection [WIfI])—on a scale of 0 to 3, where 0 represents none, 1 mild, 2 moderate, and 3 severe. [39] The wound component evaluates ulceration and gangrene. The ischemia component addresses hemodynamics and perfusion by measuring ABI, ankle systolic pressure, toe pressure, or transcustaneous oxygen tension. The foot infection component assesses clinical manifestations of infection, including extent, depth, and systemic inflammatory response.
-
Pressure ulcer of heel exacerbated by infrainguinal arterial occlusive disease.
-
Cyanosis of first toe and dependent rubor of foot, characteristic of arterial insufficiency.
-
Contrast angiogram showing severe atherosclerotic disease in distal superficial femoral artery.
Tables
Rutherford Category |
Fontaine Grade |
Clinical Description |
Objective Criteria |
0 |
0 |
Asymptomatic – No hemodynamically significant disease |
Normal treadmill or reactive hyperemia test |
1 |
|
Mild claudication |
Completes treadmill exercise (5 min at 2 mph on 12% incline) AP* after exercise >50 mm Hg but at least 20 mm Hg lower than resting value |
2 |
I |
Moderate claudication |
Between Rutherford categories 1 and 3 |
3 |
|
Severe claudication |
Cannot complete treadmill exercise and AP after exercise < 50 mm Hg |
4 |
II |
Ischemic rest pain |
Resting AP < 40 mm Hg, flat or barely pulsatile ankle or metatarsal PVR**; TP † < 30 mm Hg |
5 |
III |
Minor tissue loss (nonhealing ulcer, focal gangrene with diffuse pedal ischemia) |
Resting AP < 60 mm Hg, ankle or metatarsal PVR flat or barely pulsatile; TP < 40 mm Hg |
6 |
|
Major tissue loss (extending above transmetatarsal level, functional foot no longer salvageable) |
Same as Rutherford category 5 |
*AP = Ankle pressure. **PVR = Pulse-volume recording. † TP = Toe pressure. |
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Lesion Type |
Description |
A |
|
B |
|
C |
|
D |
|
