Thrombolysis in Acute Limb Ischemia


Acute limb ischemia (ALI) arguably presents one of the most challenging problems that vascular surgeons face. The diagnosis is often clinical, but the etiology and appropriate treatment strategy are not always straightforward. A missed or delayed diagnosis can have grave consequences, such as limb loss or even death. Its estimated incidence is 1.5 cases per 10,000 people annually. Each patient’s physical examination will vary based on etiology, time of insult, and level of occlusion. This may range from asymptomatic to profound ischemia, depending on the presence of collateral flow ( Table 31.1 ). As a general rule, the severity of the ischemia typically determines the urgency and type of revascularization. While open surgery remains the gold standard, over the past couple decades, endovascular interventions have expanded and may eventually dominate the field. The purpose of this chapter is to describe the role, indications, and outcomes of endovascular interventions in patients presenting with lower extremity acute limb ischemia, primarily focusing on complications and strategies to avoid them.

Table 31.1

Rutherford classification of severity, signs, and symptoms of acute limb ischemia.

From Earnshaw JJ. Acute Ischemia. In: Cronenwett JL, Johnston KW, et al. Rutherford’s Vascular Surgery , 8th ed. Philadelphia: Saunders; 2014:2518–2543.

Symptoms/findings Doppler signals
Category Description/prognosis Sensory Motor Arterial Venous

  • I.


Not immediately None None Audible Audible

  • II.


  • a.


Salvageable if promptly treated Minimal None Inaudible Audible

  • b.


Salvageable with immediate revascularization Rest pain Mild Inaudible Audible

  • III.


Major tissue loss or permanent nerve damage Anesthetic Paralysis Inaudible Inaudible

Acute Limb Ischemia Treatment Alternatives

The mainstay of treatment for ALI is expeditious prevention of clot propagation and reversal of ischemia. Anticoagulation is paramount and should be started immediately to prevent secondary thrombosis. Common practice is a bolus of 100 units/kg of unfractionated heparin (UFH) following by an infusion of 18 units/kg/h.

Class II and class III ischemia require immediate intervention, and patients should be transferred to a hospital with the full gamut of vascular options. Historically, class IIB ischemia is a criterion for open surgical intervention because it can restore perfusion more rapidly than traditional catheter-directed therapy (CDT). However, new studies suggest that advances in endovascular therapy, such as high-dose/accelerated CDT or pharmacomechanical thrombolysis (PMT), may offer times comparable to reperfusion as surgical therapy, which will be discussed later. (See Fig. 31.1 for the recommended ALI treatment algorithm.)

Box 31.1

Computed tomography angiograms (CTA) may aid in a diagnosis and operative planning, but it is based on physician preference. It is our preference to reserve CTA for patients with diminished femoral pulses, complicated surgical history, or multiple bypasses.

Fig. 31.1

Treatment algorithm for acute limb ischemia separated by Rutherford degree of ischemia. Rutherford class IIB ischemia is classically treated with surgical revascularization, but with the development of advanced endovascular techniques, catheter-directed therapy (CDT) or pharmacomechanical thrombolysis (PMT) may be the treatment option of choice for some surgeons. This is depicted with a dashed line .

(Figure adapted from Rutherford RB. Clinical staging of acute limb ischemia as the basis for choice of revascularization method: when and how to intervene. Sem Vasc Surg 2009;22(1):5–9.)

Surgery versus Catheter Intervention

The debate between surgical revascularization and endovascular thrombolysis has been ongoing since the 1990s, with two randomized control trials (RCTs) serving as the foundation. Post hoc analysis of one of the RCTs—the Surgery versus Thrombolysis for Ischemia of the Lower Extremity (STILE) trial—concluded that in patients with symptoms of ischemia of 14 days or less had better amputation-free survival at 6 months with thrombolysis over surgery. In the Thrombolysis or Peripheral Arterial Surgery (TOPAS) trial, the rates of limb salvage and death were comparable. In both trials, the rates of hemorrhage and complications were higher in the thrombolysis groups. Despite no clear superiority in 30-day limb salvage or mortality, surgery continues to be performed 3–5 times more often than CDT, based on European and United States national registry data, and are likely secondary to the feared complications that will be discussed later in this chapter.

University of Pittsburgh Medical Center (UPMC) Experience

It is our practice to take most patients with aortoiliac and femoral occlusions for open thromboembolectomy. Postintervention angiogram is on a physician preference basis, but generally if back bleeding is poor, or there are concerns for advanced peripheral arterial disease, or there are no distal doppler signals, angiography is obtained. At this point, chronic disease can be treated either with endovascular means or open surgery, or if distal embolization is evident, a 2–4 mg bolus of recombinant-tPA (rtPA) can be used to lyse some of the occluded outflow. If the result remains unsatisfactory, however, popliteal or pedal cutdowns may be necessary.

The benefit of surgical intervention is expeditious revascularization, but the rapidity of reperfusion needs to be weighed against the complications seen with open surgery and the inability to clear smaller outflow vessels. In our experience, which is summarized in a 2015 retrospective review of open surgery versus endovascular therapy for ALI, 326 acute limbs (classes I–III ischemia) underwent open surgery with 87%–91% technical success, which was significantly higher than CDT or PMT. However, there was no difference in amputation rates and, compared with patients who were managed with endovascular techniques, surgical patients had significantly higher 30-day and 1-year mortality, wound infection, rethrombosis, fasciotomy, return to the OR, postoperative renal failure, and new hemodialysis rates. Additionally, their lengths of stay were also extended by an average of 3 days.

Catheter-Directed Lysis

The principle behind CDT is the dissolution of clots to uncover the underlying lesion that caused thrombosis. Additionally, it offers the advantage of lysing both large and small arteries, potentially providing better run-off. The likelihood of successful reperfusion with CDT increases when the occlusion is less than 14 days old, the thrombus is easily crossed by a wire, the graft being lysed has been patent for at least 1 year, and if a culprit lesion is found and can be treated ( Fig. 31.2 ). In fact, one study reported a 2-year native vessel patency rate after lysis of 79% if a lesion was found and treated versus 9.8% if no lesion was found.

Fig. 31.2

(A) Initial angiogram of a 73-year-old woman with a previous popliteal stent graft for rest pain who presented with ALI and found to have occluded stent. (B) A Cragg-McNamara catheter embedded within the in-stent thrombosis. (C) Culprit lesions uncovered after 12 hours of catheter-directed therapy seen at proximal and distal ends of the stent graft (arrows) . (D) Completion angiogram after drug-coated balloon angioplasty to both lesions with minimal residual stenosis.

The authors’ practice is to access the contralateral femoral artery with a single puncture in a retrograde fashion, typically under ultrasound guidance in order to minimize the likelihood of puncture site hematomas. Diagnostic images are obtained to evaluate the extent of thrombosis and the quality of the outflow. After the extent of thrombosis is defined, a 4- or 5-French Cragg-McNamara (Covidien, Mansfield, Massachusetts) multi-side-hole catheter is embedded in the thrombus. If the clot extends into the tibial vessels, a ProStream (Covidien, Mansfield, Massachusetts) infusion wire is used in a coaxial manner ( Fig. 31.3 ). Although there is controversy over the dose and rate of thrombolytic delivery, the author uses a 2–4-mg bolus of rtPA followed by an infusion rate of 0.25–1.00 mg/h through each catheter. UFH at 500 units/h is infused through the sheath to prevent pericatheter thrombosis. Follow-up angiography is performed 6–12 hours later. During the follow-up angiogram, depending on the rate of clot clearance, the operator may opt to continue lysis by repositioning the catheters or finalize the procedure by ballooning or stenting uncovered lesions as needed.

Fig. 31.3

(A) Angiogram of the thrombosed outflow of the same 73-year-old woman with an occluded popliteal stent. (B) Anterior tibial (AT) artery with thrombus. (C) A Cragg-McNamara catheter was placed within the clotted stent (white arrow) with a co-axial Pro-Stream wire (black arrow) placed into the AT. (D) Completion angiogram after 12 hours of catheter-directed therapy demonstrating 3-vessel outflow without stenosis.

While infusion catheters are in place and lytic agents are actively being administered, ICU management is commonly advocated. Continuous monitoring of vitals and neurologic status are essential. Any change in neurologic exam or sudden headache should be treated like a hemorrhagic stroke until ruled out by CT scan. The ICU can also provide hourly access site surveillance to ensure no growing hematomas and to perform regular neurovascular checks to evaluate the progress of lysis. Controversy exists on whether laboratory monitoring is essential. It is the authors’ practice to check hemoglobin and fibrinogen levels every 6 hours and to titrate the infusion rate with precipitous drops in fibrinogen. If levels decrease by 50%, the infusion rate is generally halved. At fibrinogen levels below 100 mg/dL, the infusion rate is decreased to 0.25 mg/h or paused entirely.

Patients are routinely kept on either clear liquid diets or no food at all. They are maintained on bedrest while the femoral sheath is in place, with the leg kept straight to decrease risk of puncture site hematoma. A Foley catheter can be utilized, which will also help with urine output monitoring.

Intravenous hydration while restoring flow to an acutely ischemic limb is essential. Reperfusion of the ischemic limb leads to release of acidic metabolites and myoglobin and can lead to metabolic derangement and/or renal failure. Patient education is also tantamount. Patients undergoing CDT should be informed that their pain may wax and wane with microembolization and then subsequent lysis of emboli. If PMT is used, tea-colored urine may result from red blood cell lysis. This is especially true with the AngioJet device discussed in the following section.

Pharmacomechanical Thrombectomy

One of the limitations of CDT is the time to reperfusion may not be rapid enough to prevent irreversible neuromuscular injury. This is precisely why Rutherford IIB ischemic patients generally undergo open surgery rather than lysis. However, since the advent of CDT, innovation has introduced endovascular mechanical clot removal devices that can be considered in conjunction with pharmacologic thrombolytics to accelerate clot dissolution and, in turn, decrease the dose of lytic agent given. Below are the three most widely used catheters for PMT in ALI.


The AngioJet Thrombectomy System (Boston Scientific, Maple Grove, Minnesota) is a rheolytic device that produces high-pressure jets of saline to fragment thrombus at the tip of the catheter, which, in turn, creates a relative low-pressure area that acts a suction tip whereby clot particles can be removed from the body. The PEARL Registry (PEripheral use of AngioJet Rheolytic thrombectomy with a variety of catheter Lengths) prospectively enrolled 283 patients with ALI who were treated with the AngioJet with or without CDT. Approximately 26% of patients presented with class I ischemia, 38% with class IIA, and 35% with class IIB. Overall, there was 83% success, defined as not requiring open surgery. Those who underwent PMT completed their surgery in one session, had shorter procedures, and received significantly less thrombolytic agents. Amputation-free survival at 6 and 12 months were 85% and 81%, respectively. Safety outcomes were similar to other PMT studies, with 4.3% of major bleeding requiring transfusion. A caveat to note is that 80% of the patients enrolled in the PEARL registry had symptoms for 7 days or less, which may have contributed to high success rates.

UPMC Experience

Our experience with PMT for ALI is predominantly with the AngioJet catheter for femoral–popliteal thrombus, followed by CDT for residual thrombus. Although some surgeons prefer to use embolic protection devices (EPDs), we generally do not. Instead, the AngioJet is initially used to clear the proximal clot without crossing the distal cap to avoid potential distal embolization. This is done with power pulse mode with 6–12 mg of rtPA in 100–250 mL of normal saline, followed by thrombectomy mode after 15–20 minutes dwell time. The distal cap is crossed after clearance of the proximal thrombus. In our retrospective review of 154 limbs that received CDT versus PMT, there was a significant difference in technical success favoring PMT (90.1% versus 78.3%). Although not statistically significant, more instances of embolization occurred in the PMT group (14% versus 6%). However, there was no difference in duration of lysis, amputation, patency, or mortality at 2 years. With regards to complications, there was a significant difference in rates of access site hematoma, with more occurring in the PMT group. There were also three occurrences of transient acute renal failure in the PMT group and none in the CDT group. This figure did not reach significance. We therefore conclude that PMT offers increased chance of technical success compared with CDT and similar clinical and patency outcomes. However, we proceed with caution in patients with renal insufficiency.


The Penumbra/Indigo system (Penumbra, Alameda, California) is an aspiration thrombo-embolectomy catheter available in sizes 3- to 8-French that is vacuum-driven for consistent suction and first became available in 1985 as an alternative to balloon embolectomy ( Box 31.2 ). The PRISM trial was a single-arm, multicenter, retrospective review of 79 patients who underwent endovascular suction thrombectomy as either initial or adjunctive therapy after other revascularization attempts. Standard technique is to place the tip of the catheter at the proximal edge of the thrombus and begin aspiration. Technical success was measured by angiographic assessment using a Thrombolysis in Myocardial Infarction (TIMI) score with 0 meaning no perfusion and 3 meaning complete perfusion. Ninety-nine percent of cases began with a TIMI score of 0–1 and use of the Penumbra thrombectomy catheter improved TIMI grade to 2–3 in 87.2% of patients. There were no long-term outcomes described. Complications included anemia, compartment syndrome, and other medical complications, including renal insufficiency, confusion, and respiratory failure.

Apr 3, 2021 | Posted by in VASCULAR SURGERY | Comments Off on Thrombolysis in Acute Limb Ischemia

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