Alteplase for Acute Limb Ischemia
Catheter-directed thrombolysis (CDT) with alteplase is an effective treatment option for acute limb ischemia, particularly in patients with Rutherford class IIa and IIb ischemia, achieving technical success rates of 76-84% with acceptable bleeding risks when used via intraarterial infusion. 1, 2
Treatment Protocol and Dosing
The most effective protocol involves catheter-directed intraarterial infusion of 40 mg alteplase over 3.5 hours, which has been successfully utilized in 92% of cases in contemporary vascular surgery practice. 1 This accelerated protocol differs substantially from stroke dosing and should never be confused with the 0.9 mg/kg IV protocol used for acute ischemic stroke. 3, 4
Alternative dosing strategies include:
- Median dose of 5 mg with continuous infusion at 2 mg/hour for more prolonged therapy 5
- Both intravenous and catheter-directed approaches show comparable clinical outcomes, though CDT achieves significantly superior angiographic improvement 2
Patient Selection Criteria
Ideal candidates for alteplase thrombolysis in acute limb ischemia include:
- Age <75 years 2
- Symptom duration <14 days 2
- Rutherford classification IIa or IIb (threatened but viable limb) 6, 2
- Absence of complete distal runoff 2
Critical exclusion factors:
- Rutherford class III (irreversibly damaged limb) - these patients require immediate surgical intervention or amputation 6
- Severe malnutrition (CONUT score ≥2) - associated with failed thrombolysis and increased bleeding risk 7
Expected Outcomes
Technical success rates:
- Immediate technical success (TIMI grade 2/3): 56-76% 1, 2
- Overall technical success after adjunctive procedures: 84% 1
- Clinical success at 30 days: 74.5% 1
Important caveat: Approximately 67-70% of successful thrombolysis cases require additional endovascular interventions to address underlying lesions. 5, 1 Do not consider thrombolysis alone as definitive therapy - plan for angioplasty, stenting, or surgical bypass as needed.
Complications and Safety Profile
Major bleeding occurs in 5-12% of patients, with the higher rate including access site hematomas. 1, 7 Critically, neither intracranial hemorrhage nor gastrointestinal bleeding occurred in the largest contemporary series. 1
Other significant complications include:
- Amputation rate at 30 days: 10.7-12.7% 1, 7
- In-hospital mortality: 2.5-5.1% 5, 1
- Distal embolization: 7.14% 5
- Compartment syndrome and reperfusion injury (monitor closely) 6
Predictors of Treatment Failure
Factors associated with insufficient lytic response:
- Malnutrition (CONUT score ≥2) - strongest independent predictor 7
- Symptom duration >24 hours 2, 7
- Rutherford class 4/5 symptoms 7
- Thrombus location in crural (below-knee) arteries 1
- Worsened distal runoff 7
Atrial fibrillation increases amputation risk, while complete thrombus lysis is protective against amputation. 1
Critical Timing Considerations
Both ankle-brachial index (ABI) and pain scores improve significantly when alteplase is administered within 24 hours of symptom onset. 2 Beyond this window, efficacy diminishes but treatment may still be attempted in carefully selected patients with symptoms up to 14 days. 2
Comparison to Surgical Revascularization
Catheter-directed thrombolysis is not a replacement for surgery but rather a complementary option. 6 For Rutherford class I (viable limb without immediate threat), either approach is reasonable; for class IIa/IIb, CDT is preferred when available; for class III, immediate surgery is mandatory. 6
Common Pitfalls to Avoid
- Do not use stroke dosing protocols (0.9 mg/kg IV) for limb ischemia - this is incorrect and potentially harmful 3, 4
- Do not attempt thrombolysis in malnourished patients without recognizing increased failure and bleeding risk 7
- Do not rely on thrombolysis alone - plan for adjunctive endovascular or surgical procedures in most cases 5, 1
- Do not delay treatment beyond 24 hours when possible, as outcomes deteriorate significantly 2
- Do not forget to monitor for compartment syndrome after successful reperfusion 6