Page 2374 - Hematology_ Basic Principles and Practice ( PDFDrive )

2116 Part XII Hemostasis and Thrombosis

TABLE Clinical Outcomes in Patients With Acute or Chronic Limb Ischemia Treated by Catheter-Directed Thrombolysis or Surgery in
143.1 the STILE Trial
Acute Ischemia (≤14 days), n = 112 Chronic Ischemia (>14 days), n = 266
Surgery (%) Lysis (%) p-Value Surgery (%) Lysis (%) p-Value
Death 10.0 5.6 0.45 7.9 6.9 0.81
Amputation 30.0 11.1 0.02 3.0 12.1 0.01
Death + amputation 37.5 15.3 0.01 9.9 17.8 0.08

thrombosis is approximately 15% and the amputation rate ranges with surgery. However, there was more bleeding with CDT than with
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from 10% to 30%. In one study, the time from diagnosis to treat- surgery.
ment correlated with amputation rates: 6% if thrombolytic therapy The Surgery versus Thrombolysis for Ischemia of the Lower
was started within 12 hours of symptom onset, 12% if started within Extremity (STILE) trial included 393 patients who either underwent
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13–24 hours, and 20% if started after 24 hours. 9 CDT with urokinase or rt-PA, or surgery. In patients with acute
ischemia, CDT was associated with significantly fewer amputations,
increased amputation-free survival at 1 year, and a shorter hospital
Rationale, Benefits, and Risks of CDT for PAO stay. However, in those with chronic ischemia, surgery was associated
with fewer amputations and improved amputation-free survival
The traditional treatment for acute limb ischemia is open surgery. (Table 143.1). In a subgroup analysis, the patients with acute bypass
However, the emergent nature of these procedures and the character- graft occlusions had a significantly lower rate of amputations com-
istics of the affected patient population, which tends to have high pared with those patients who underwent surgery. These data suggest
rates of concomitant coronary and cerebrovascular disease, have that patients with acute bypass occlusion may derive the greatest
contributed to significant rates of perioperative complications and benefit from CDT.
death. By dissolving platelet–fibrin aggregates in the microcirculation The Thrombolysis or Peripheral Arterial Surgery (TOPAS) trial
and thrombi in collateral vessels, CDT allows rapid but gradual randomized 544 patients with acute limb ischemia to CDT with
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reperfusion of the distal limb, thereby minimizing the risk of reperfu- recombinant urokinase or to surgery. There was no difference in
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sion complications and compartment syndrome. CDT enables both amputation-free survival at 1 year. However, CDT was associated
rapid restoration of arterial blood flow to the ischemic limb and with more bleeding complications, including a 1.6% rate of intra-
unmasking of arterial stenotic or occlusive lesions that require treat- cranial hemorrhage.
ment. Because many such lesions can be treated with endovascular In summary, the results of these three trials suggest that CDT
techniques, such as balloon angioplasty or stent placement, CDT reduces the need for amputation and surgical intervention in patients
allows many patients to avoid the risks and inconveniences of open with acute limb ischemia, particularly those with acute bypass graft
surgery. When surgery is required, a more limited procedure can occlusion. However, the risk of bleeding is higher with CDT than
often be performed on an elective basis in a well-prepared patient, with surgery. Although outcomes in patients with acute limb ischemia
with reduced rates of complications and death. are better with CDT, surgery is recommended for those with chronic
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The major complication of CDT is bleeding. In the setting of ischemia. Because revascularization of nonviable limbs can precipitate
PAO, the incidence of CDT-related hemorrhagic stroke is approxi- a reperfusion syndrome associated with release of potassium, myoglo-
mately 1%. The rate of major hemorrhage, defined by hypotension, bin, and other toxic elements from the nonviable limb, which can
need for surgical therapy, or need for blood transfusion, is approxi- lead to multiorgan damage and death, patients with nonviable limbs
mately 5%, with minor hemorrhage (e.g., local hematoma) occurring (Rutherford class III) generally require primary amputation.
in 15% of patients. In modern practice, the use of subtherapeutic
doses of heparin during thrombolysis may help to minimize bleeding
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complications. Distal embolization of thrombus fragments occurs PMT, PCDT, and Ultrasound-Assisted CDT for
in about 5% of cases; most of these resolve with continued lytic Arterial Thrombosis
therapy. However, worsening ischemia can occur and generally
requires percutaneous thrombus aspiration or operative intervention There is a paucity of data concerning the relative effectiveness and
if the condition does not improve with thrombolysis within a few safety of newer thrombolytic techniques for PAO. The AngioJet
hours. Compartment syndrome, a complication that results from device is FDA approved for peripheral arterial thrombus removal and
rapid reperfusion of the ischemic limb, occurs in 2% of patients. is routinely utilized as an adjunct to CDT. There are limited data
Death occurs in less than 1% of patients, usually in the setting of related to the safety and efficacy of the AngioJet, Trellis, and Ekosonic
intracranial or abdominal hemorrhage, or reperfusion syndrome. devices for the treatment of PAO. Aside from bleeding, the major
Complications of CDT, which usually are minor, can also be related complications associated with PMT and PCDT are distal emboliza-
to intraarterial catheter insertion. Catheter-related trauma, resulting tion and local vascular injury (i.e., dissection or rupture). Although
in mural dissection, puncture site pseudoaneurysm, and/or major there are no randomized PAO trials comparing ultrasound-accelerated
hematoma occurs in 1%–2% of patients. CDT with standard CDT, preliminary data from several studies
suggest that ultrasound-accelerated CDT significantly reduces treat-
Randomized Trials: CDT Versus Surgery for ment time without increasing the rate of serious adverse events when
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compared with CDT alone.
Arterial Thrombosis A multicenter registry of 99 patients treated with AngioJet
reported substantial or complete revascularization (defined as <50%
Three randomized controlled trials compared clinical outcomes in residual defect) in 70% of patients and in-hospital and 30-day
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patients with acute PAO who were randomized to receive either CDT mortality rates of less than 5%. Another study documents higher
or surgical intervention. amputation-free success rates associated with initial endovascular
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The Rochester trial randomized 114 patients presenting with PCDT procedures, with low repeat intervention rates. However,
acute limb ischemia to catheter-directed urokinase infusion or these studies are limited by methodological deficiencies including
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surgery. While there was no difference in limb salvage rates at 1 lack of randomization. Studies using the Trellis device are limited and
year, mortality at 1 year was significantly lower with urokinase than only case reports have described its use for acute limb ischemia; given