What is the recommended alteplase (recombinant tissue‑type plasminogen activator) dosage and heparin regimen for catheter‑directed thrombolysis in a patient with acute limb ischemia who has no absolute contraindications to fibrinolysis?

Catheter-Directed Thrombolysis Dosing for Acute Limb Ischemia

For catheter-directed thrombolysis in acute limb ischemia, administer alteplase (rt-PA) as a 5-15 mg initial bolus followed by continuous infusion at 0.5-1 mg/hour (maximum 2 mg/hour), with concurrent unfractionated heparin bolus of 60 U/kg (maximum 4000 U) followed by infusion at 12 U/kg/hour (maximum 1000 U/hour) targeting aPTT 50-70 seconds. 1, 2

Alteplase Dosing Protocol

Initial Bolus

• Administer 5-15 mg of alteplase as an initial bolus injection directly into the thrombus through the catheter 2
• The bolus dose varies based on thrombus burden and location 2

Continuous Infusion

• Follow with continuous infusion at 0.5-1 mg/hour, with maximum rate of 2 mg/hour 1, 2
• Taper the infusion rate as lysis progresses 2
• Mean duration of completed infusions is approximately 21 hours (range 2-58 hours) 2

Alternative Accelerated Protocol

• An accelerated protocol using 40 mg of alteplase infused over 3.5 hours has demonstrated 76.1% success rate with only 5% major bleeding complications 3
• This accelerated approach is effective for acute, subacute limb ischemia and thrombotic complications of vascular procedures 3

Concurrent Heparin Regimen

Unfractionated Heparin Dosing

• Initial bolus: 60 U/kg (maximum 4000 U) 1
• Continuous infusion: 12 U/kg/hour (maximum 1000 U/hour) 1
• Target aPTT: 50-70 seconds 1
• Monitoring schedule: Check aPTT at 3,6,12, and 24 hours after initiation 1

Rationale for Heparin

• Heparin prevents thrombus propagation and provides anti-inflammatory effects that lessen ischemia 4
• Immediate systemic anticoagulation with heparin is a Class I recommendation regardless of facility limitations 4
• Unfractionated heparin's short half-life and titratability make it the preferred agent during thrombolysis 5

Agent Selection

Preferred Thrombolytic: rt-PA or Urokinase

• The American College of Chest Physicians recommends rt-PA or urokinase over streptokinase (Grade 2C) 1
• Streptokinase has been largely replaced due to increased amputation rates (RR 7.0) and allergic reactions 1
• No significant difference exists between rt-PA and urokinase in terms of amputation, limb salvage, major hemorrhage, or death 1

Patient Selection Criteria

Appropriate Candidates (Rutherford Categories I and IIa)

• Patients with viable limbs (Category I) or marginally threatened limbs (Category IIa) are ideal candidates 6, 2
• CDT is the treatment of choice for these patients with no contraindications to thrombolytic therapy 6
• Technical success rate reaches 80% when ischemic symptom onset is within 6 weeks 2

Emergent Revascularization (Rutherford Category IIb)

• Patients with immediately threatened limbs (Category IIb) require emergent revascularization within 6 hours 4
• CDT may still be considered if relative risks compared with primary operation are favorable 6

Monitoring During Infusion

Clinical Assessment

• Perform serial angiography every 4-8 hours to assess thrombus resolution 6
• Monitor for signs of reperfusion, including pain relief and return of Doppler signals 4
• Assess for compartment syndrome development, which requires fasciotomy 1, 5

Laboratory Monitoring

• Check aPTT at 3,6,12, and 24 hours to maintain therapeutic range of 50-70 seconds 1
• Monitor fibrinogen levels; consider stopping thrombolysis if fibrinogen drops below 100 mg/dL 6
• Assess for metabolic abnormalities including acidosis and hyperkalemia from reperfusion 5

Expected Outcomes

Efficacy

• Technical success rate: 75.7-81.8% 7, 2
• 30-day amputation-free survival: 86.5% 2
• 1-year limb salvage: 72.7-78.4% 7, 2
• 30-day mortality: 4.2-10.8% 8, 2

Complications

• Major bleeding requiring >4 units transfusion: 5.4% 2
• Intracranial hemorrhage: 2.7-5.4% 2
• Minor bleeding/access site hematoma: 18.9% 2
• Overall complication rate: 28.7% 8

Adjunctive Interventions

Additional Procedures

• Approximately 67.8% of patients require adjunctive percutaneous intervention or arterial bypass after successful thrombolysis to address underlying stenotic lesions 2
• Secondary interventions are needed in 77.8% of cases 8
• Balloon angioplasty is required in 36.4% of patients with distal occlusions 7

Common Pitfalls to Avoid

Critical Errors

• Do not delay heparin initiation: Immediate systemic anticoagulation is mandatory and should not wait for vascular consultation or imaging 4
• Do not use streptokinase: It increases amputation risk 7-fold and causes allergic reactions; antibodies persist for at least 10 years 1
• Do not re-administer fibrinolytics for reocclusion: If reocclusion occurs, proceed directly to mechanical intervention rather than repeat thrombolysis 1
• Do not overlook compartment syndrome: Monitor closely and perform fasciotomy promptly after revascularization to prevent limb loss 1, 5

Timing Considerations

• Skeletal muscle tolerates ischemia for only 4-6 hours, making every minute critical 4
• Category IIa/IIb limbs require revascularization within 6 hours 4
• Technical success decreases significantly when symptom onset exceeds 6 weeks 2

Bleeding Risk Management

• Major intracranial hemorrhage risk is 2.7-5.4%, with all reported nonfatal strokes in thrombolysis groups being intracranial hemorrhages 1, 2
• The accelerated protocol (40 mg over 3.5 hours) demonstrates lower major bleeding rates (5%) compared to traditional prolonged infusions 3
• Atrial fibrillation increases amputation risk and requires careful consideration 3