What is the recommended intravenous alteplase dose for a hemodynamically unstable adult with massive pulmonary embolism and how should subcutaneous low‑molecular‑weight heparin be administered afterward?

Alteplase Dosing and LMWH Management in Massive Pulmonary Embolism

Alteplase Dosing Protocol

For massive pulmonary embolism with sustained hypotension (systolic BP <90 mmHg for ≥15 minutes), cardiogenic shock, or need for vasopressors, administer alteplase 100 mg as a continuous intravenous infusion over 2 hours via a peripheral vein. 1, 2

Cardiac Arrest or Imminent Collapse

• If the patient is in cardiac arrest or rapidly deteriorating with imminent arrest, give alteplase 50 mg as an immediate IV bolus over 2-15 minutes and continue CPR for at least 30 minutes. 1, 2
• Do not use the 100 mg infusion protocol during active cardiac arrest—the 50 mg bolus is the correct regimen for this scenario. 1, 2
• Reassess at 30 minutes after the bolus to evaluate return of spontaneous circulation and ongoing right ventricular dysfunction. 1

Alternative Dosing Regimens

• An alternative regimen of 0.6 mg/kg over 15 minutes (maximum 50 mg) has been studied and shows comparable efficacy to the 100 mg/2-hour infusion, though the FDA-approved dose remains 100 mg over 2 hours. 3
• The 100 mg over 2 hours regimen is preferred as the standard of care based on FDA approval and guideline recommendations. 1, 2

LMWH Administration After Thrombolysis

Withhold all anticoagulation (including LMWH) during the 2-hour alteplase infusion, then resume therapeutic anticoagulation 3 hours after completion of the infusion. 1, 2, 4

Preferred Anticoagulation Strategy

• Unfractionated heparin (UFH) is traditionally preferred over LMWH immediately after thrombolysis in massive PE because it allows rapid reversal if bleeding occurs and has more predictable pharmacokinetics in hemodynamically unstable patients. 4
• Start UFH with an 80 IU/kg IV bolus followed by 18 IU/kg/hour continuous infusion, targeting an aPTT of 1.5-2.5 times control. 1, 4
• The older guideline recommendation was 1280 IU/hour (approximately 15-20 IU/kg/hour) starting when aPTT falls below twice the upper limit of normal. 3

LMWH as an Alternative

• Recent evidence suggests LMWH can be used safely after thrombolysis and may actually reduce 30-day mortality compared to UFH (8.2% vs 17.3%, p=0.031). 5
• LMWH after thrombolysis showed lower rates of major hemorrhage (4% vs 7.9%) and minor hemorrhage (9% vs 13.4%) compared to UFH in a prospective multicenter trial of 249 patients. 5
• If LMWH is chosen, use therapeutic weight-based dosing (e.g., enoxaparin 1 mg/kg subcutaneously every 12 hours or 1.5 mg/kg once daily) starting 3 hours after alteplase completion. 5

Critical Decision Points

When to Proceed Without Imaging

• Do not delay thrombolysis for imaging confirmation when the patient is in cardiac arrest, peri-arrest, or shock with high clinical suspicion of massive PE. 1, 2
• High clinical suspicion combined with bedside echocardiography showing right ventricular dysfunction is sufficient to proceed with alteplase when the patient is too unstable for CT pulmonary angiography. 1, 2

Contraindications in Life-Threatening PE

• In truly massive PE with hemodynamic collapse, most traditional contraindications to thrombolysis should be overridden because untreated mortality is 52-65%. 1, 2
• Absolute contraindications that must still be respected include prior intracranial hemorrhage, known structural cerebral vascular lesion, and acute ischemic stroke within 6 months. 2
• When absolute contraindications exist, pursue immediate surgical embolectomy or catheter-directed therapy rather than withholding reperfusion. 2, 4

Common Pitfalls to Avoid

• Do not give fluid boluses aggressively in massive PE—this worsens right ventricular failure by increasing preload against an already obstructed pulmonary circulation. 2
• Do not wait for pulmonary angiography before thrombolysis in unstable patients—it is time-consuming, hazardous, and increases bleeding risk. 1
• Do not use direct oral anticoagulants (DOACs) acutely in hemodynamically unstable PE, as UFH or LMWH may be required for subsequent interventions. 1
• Major bleeding occurs in 10-40% of patients receiving alteplase, but intracranial hemorrhage risk is approximately 2%. 1, 2

Monitoring During and After Thrombolysis

• Continuous cardiac monitoring with serial blood pressure measurements and oxygen saturation monitoring is essential. 4
• Monitor for bleeding complications with periodic laboratory assessment including hemoglobin, hematocrit, and coagulation parameters. 4
• Check aPTT 4-6 hours after starting UFH to ensure therapeutic anticoagulation (1.5-2.5 times control). 3, 4