Acute Limb Ischemia: Pharmacomechanical and Thrombolytic Therapy
M. Fuad Jan
Mark W. Mewissen
Intra-arterial Catheter-Directed Thrombolytic Therapy
Pioneered by Dotter in the 1970s, intra-arterial (IA) thrombolysis has become a routine medical practice in the emergent treatment of an acutely ischemic limb with the goal of rapidly restoring blood flow to the endangered limb (Fig. 14.1). Prethrombolytic angiography also helps identify the underlying culprit lesion(s) for treatment by surgery and/or percutaneous endovascular methods.
Contraindications
1. Active or recent internal bleeding including gastrointestinal bleeding (within 10 days)
2. Irreversible limb ischemia with major tissue loss or permanent nerve damage (severe sensorimotor loss, paralysis/muscle rigor)
 FIGURE 14.1 • Algorithm for the evaluation and management of acute limb ischemia (ALI). Once diagnosed, anticoagulation is initiated with subsequent treatment depending on classification of the ALI. Initial options include catheter-directed thrombolysis (CDT) with or without percutaneous mechanical thrombectomy (PMT) or surgical revascularization. Clinical categories of ALI include limbs that are (a) viable, with no immediate threat of tissue loss, intact muscle power and sensations, and audible arterial/venous Doppler signals; (b) marginally threatened, with a threat of tissue loss, minimal or no sensory loss, intact muscle power weak, and often inaudible arterial Doppler signals but intact venous Doppler signals (treated promptly, these limbs are salvageable; these limbs afford time for vascular imaging); (c) immediately threatened and need prompt attention without delay and manifest as limbs with sensory (more than the toes) and motor loss (mild to moderate) with inaudible arterial Doppler signals but audible venous Doppler signals; these limbs are salvageable; and (d) irreversibly ischemic or nonviable, with major tissue loss, profound sensory and motor loss (paralysis), and inaudible arterial/venous Doppler signals. |
Table 14.1 Classification of Acute Limb Ischemia | ||||||||||||||||||||||||||||||||||||||||||
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3. Recent stroke (arbitrary guideline: transient ischemic attack [TIA] within 2 months or cerebrovascular accident [CVA] within 6 months; some prefer to wait up to 12 months)
4. Intracranial neoplasm or recent neurosurgery (within 3 months)
5. Protruding mobile left heart thrombus
Although thrombolysis is not usually considered in the following conditions, clinical decision making revolves around the anticipated benefit and attendant risks. Careful clinical evaluation and sound judgment in patient selection, especially elderly patients, are essential.
1. History of gastrointestinal bleeding
2. Recent major nonvascular surgery (10 days), including biopsy
3. Recent trauma
4. Recent (10 days) episode of cardiopulmonary resuscitation (CPR)
6. Emboli from cardiac source (obtain echocardiogram if suspected)
7. Subacute bacterial endocarditis
8. Coagulopathy
9. Pregnancy and postpartum period (<10 days)
10. Severe cerebrovascular disease
11. Diabetic hemorrhagic retinopathy
Preprocedure Preparation
1. Good-quality noninvasive imaging (color Doppler ultrasound, multidetector computerized tomography, or magnetic resonance angiography) “may” have an important role prior to the initiation of IA thrombolysis by defining the distribution of disease.
2. Standard laboratory evaluation includes hematocrit (Hct)/hemoglobin (Hgb) (>10 gm per dL and 30% by volume), platelet count (>100,000 per µL), baseline blood urea nitrogen (BUN)/creatinine (Cr), prothrombin time (PT) with international normalized ratio (INR), partial thromboplastin time (PTT) (alternatively, activated clotting time [ACT]), and fibrinogen levels (optional).
3. Access site selection: Review of previous angiograms is useful for planning the access site. Occlusive disease can be approached from either the contralateral or the ipsilateral side. An ipsilateral antegrade approach may avoid catheter manipulation, facilitating complementary techniques like aspiration thromboembolectomy and balloon dilation. Careful direct puncture of a graft is usually risk-free; an axillary artery puncture should be avoided when thrombolytic therapy is anticipated.
Procedure
1. After obtaining the desired IA access and placing an IA sheath, a baseline arteriogram is performed to document the extent of the thrombus and arterial disease (Fig. 14.2).
2. After identifying the occlusion and deciding on IA thrombolysis (Fig. 14.3), the 5 Fr. short sheath (typically used initially) is replaced with a 6 Fr. crossover sheath (when possible, place tip of sheath in the external iliac artery, in case of occlusion of all lower extremity branches).
3. Attempt is next made to traverse the occlusion (using an angled 0.035-in. hydrophilic wire with or without the help of a smaller-size angled catheter, e.g., Bernstein/glide/Quick-Cross Support Catheter [Spectranetics, Colorado Springs, CO]). Progress is monitored by periodic angiography, and catheter
position is adjusted appropriately. Oblique views may help find the entry orifice of the thrombus. Once through, the wire is advanced across the thrombus well distally, and the catheter is advanced over it in order to allow exchange for a more sturdy wire.
position is adjusted appropriately. Oblique views may help find the entry orifice of the thrombus. Once through, the wire is advanced across the thrombus well distally, and the catheter is advanced over it in order to allow exchange for a more sturdy wire.
 FIGURE 14.2 • Arteriographic patterns typically corresponding to clinical acute ischemia categories: (I) Viable limbs often show a single segmental occlusion with patent collaterals and reconstitution of calf runoff vessels; (II) threatened limbs can have tandem lesions in series or in parallel with patent collaterals and reconstitution of calf runoff vessels; and (III) irreversibly ischemic limbs have extensive parallel thrombotic occlusions, occluded collaterals, and no distal reconstitution of runoff vessels. (Borrowed from McNamara TO. Thrombolysis as an alternative initial therapy for the acutely ischemic limb. Semin Vasc Surg. 1992;5:89-98.) |
4. After estimating the length of the occlusion, a thrombolytic infusion catheter is placed over the guidewire. Typically, the infusion catheter should cover the length of the occlusion and leaving a 2- to 5-cm area at either end.
a. A thrombus that is resistant to passage of a standard guidewire (guidewire traversal test or GWTT) is probably chronic and may be difficult to dissolve (6,7). However, this should not discourage an attempt at thrombolysis (1,2,3,4,5). If the catheter tip cannot be successfully placed within the thrombus, it may be placed proximal to it for a short trial of (regional) lytic therapy. This may soften the proximal thrombus for a later attempt at intrathrombic catheter placement.
b. Failure to place the catheter within the thrombus (intrathrombic catheter position) decreases the likelihood of a technically successful lysis (2,3).
5. Catheter selection: A variety of infusion catheters (e.g., Cragg-McNamara Valved Infusion catheter [Covidien, Plymouth, MN] and MicroMewi infusion catheter [Covidien, Plymouth, MN]) with different catheter and infusion lengths are available. The catheters are typically used for slow, continuous infusion of the thrombolytic.
6. Thrombolytic agents (see Table 14.2 for dose administration): CDT relies on diffusion of the agent into the thrombus, a slow process that requires a high concentration gradient to drive the reagent into the clot.
a. Several thrombolytic agents have been described in the literature, and currently none has U.S. Food and Drug Administration (FDA) approval for use in peripheral arteries or veins. Prospective randomized trials comparing the agents directly are limited and thus do not yield a meaningful comparison.
(1) UK was the most commonly used agent in the United States, but it is no longer available. rt-PA has been more widely used in Europe (8). The
literature on thrombolytic therapy reflects these preference patterns (2). Reteplase (rt-PA), a recombinant deletion mutant of rt-PA, is currently the most widely used thrombolytic agent in the United States for peripheral vascular applications (9).
literature on thrombolytic therapy reflects these preference patterns (2). Reteplase (rt-PA), a recombinant deletion mutant of rt-PA, is currently the most widely used thrombolytic agent in the United States for peripheral vascular applications (9).
 FIGURE 14.3 • Stages of IA thrombolysis. A: An occluded segment of vessel is demonstrated arteriographically. B: A coaxial catheter is introduced through the IA sheath and advanced into the proximal thrombus, and a guidewire is then advanced to the distal end of the thrombus (GWTT). C: A tip-occluded multiside-orifice catheter is advanced into the entire thrombus, which is saturated with a lacing dose of lytic agent deposited by rapid pulse-spray infusion. (Alternatively, an end-hole catheter or a catheter with fewer distal side-holes is advanced distally and then retracted proximally while depositing small doses of lytic agent at each site.) D: Continuous infusion is administered with an end-hole catheter with its tip in the proximal thrombus and a smaller side-hole catheter that is advanced much farther into the clot. (A distal untreated segment of thrombus is shown here, but a side-hole catheter, with its tip occluded, may be advanced so as to bathe the thrombus with lytic agent throughout its length.) E: As thrombolysis progresses, both catheters may be advanced, but with this configuration, the inner catheter alone may be advanced into the receding thrombus front. The process continued until the entire thrombus is dissolved and an underlying obstructing lesion is uncovered for treatment by angioplasty or surgery. |
(2) The general consensus is that UK and rt-PA are equally efficacious and safe (2,5,8), and that both are superior to SK for treating peripheral arterial occlusions (2,3,8). Tissue-plasminogen activator produces more rapid early lysis than UK (4,5,10). Although experience with peripheral thrombolysis using rt-PA is limited, the efficacy and safety profile appears to be acceptable (9).
b. Intrathrombic lacing involves depositing concentrated agent into the thrombus using multiple side-hole catheters and the pulsed-spray technique (2,3,11,12). High-dose intrathrombic lacing of the agent saturates the thrombus and significantly decreases treatment duration, total dose, and complication rates (12). Lacing is started distally, and the catheter is progressively retracted proximally. Some advocate leaving a distal plug of thrombus in place in order to avoid possible embolization caused by the forced infusion. Others lace the entire thrombus in order to reestablish flow quickly.
Table 14.2 Popular Dosing Schemes for Treatment of Peripheral Arterial Occlusions with Thrombolytic Agentsa | |||||||||
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