Alteplase is a potent fibrinolytic (thrombolytic) agent.
It is used in selected patients with acute ischaemic stroke, high-risk pulmonary embolism, and in some reperfusion pathways for STEMI, although primary PCI is preferred for STEMI whenever it can be delivered promptly. ⚠️ Alteplase is a high-risk specialist medicine because the major complication is serious bleeding, including intracranial haemorrhage.

⚙️ Mode of Action

Recombinant tissue plasminogen activator (tPA) → converts plasminogen to plasmin → breaks down fibrin-rich thrombi 🩸. It lyses clot but also increases the risk of major bleeding.
It has a short plasma half-life, so dosing is usually given as a bolus followed by infusion for some indications.

📏 Indications & Dosing (always verify locally)

Indication	Dose	Route
Acute ischaemic stroke ⏱️ Within 4.5 hours of symptom onset	0.9 mg/kg (maximum 90 mg) total dose: • 10% of total dose as an initial IV bolus • remaining 90% infused over 60 minutes	IV
High-risk / massive PE 💥 With haemodynamic instability	100 mg total over 2 hours: • 10 mg IV bolus over 1–2 minutes • then 90 mg IV infusion over 2 hours • if body weight <65 kg, total dose should not exceed 1.5 mg/kg	IV
STEMI ⏱️ Fibrinolysis pathway only, when PCI is not available in time	Accelerated regimen: • 15 mg IV bolus • then 0.75 mg/kg (maximum 50 mg) over 30 minutes • then 0.5 mg/kg (maximum 35 mg) over 60 minutes • maximum total 100 mg Alternative 3-hour regimen: • 10 mg IV bolus • then 50 mg over 1 hour • then 10 mg every 30 minutes × 4 • total 100 mg over 3 hours • if body weight <65 kg, total dose should not exceed 1.5 mg/kg	IV

💡 The regimens are not interchangeable. Stroke, PE, and STEMI use different dosing schedules, and many modern UK pathways now favour tenecteplase rather than alteplase in some stroke or STEMI settings.

🧠 Acute ischaemic stroke – practical details

Requires brain imaging first to exclude haemorrhage.
Should only be given in a well-organised stroke service with trained staff, acute imaging, and protocols for complications.
🩺 Monitor closely for neurological deterioration, angioedema, and haemorrhagic transformation.
💊 Aspirin and other antithrombotics are usually withheld for the first 24 hours after stroke thrombolysis, pending repeat imaging/local protocol.

🫁 Pulmonary embolism – practical details

Reserved for high-risk PE with haemodynamic instability, not routine stable PE.
Escalate early to critical care / respiratory / acute medicine.
Monitor for bleeding and for haemodynamic response.

❤️ STEMI – practical details

Primary PCI is preferred whenever it can be delivered promptly.
If fibrinolysis is being used, it is done as part of a specialist reperfusion pathway.
Adjunctive antiplatelet and anticoagulant therapy follows the relevant cardiology protocol.

⚠️ Interactions

Other antithrombotic drugs increase bleeding risk.
Recent or concurrent anticoagulants may make thrombolysis unsafe depending on the indication and timing.
ACE inhibitors increase the risk of orolingual angioedema after stroke thrombolysis.

🔎 Cautions

Specialist use only.
Careful patient selection is essential.
Contraindications differ according to whether alteplase is being used for stroke, PE, or MI.
Always confirm the exact protocol before prescribing or administering.

🚫 Important Contraindications (check indication-specific guidance)

🩸 Active bleeding
🧠 Previous or current intracranial haemorrhage
🫀 Suspected aortic dissection
🔪 Recent major surgery or major trauma
📈 Severe uncontrolled hypertension
🧬 Known intracranial neoplasm, AV malformation, or aneurysm in relevant settings
🧫 Significant bleeding disorder or severe thrombocytopenia

❗ Adverse Effects

🩸 Bleeding - the major risk, including intracranial haemorrhage
💧 Hypotension
😮 Angioedema / tongue swelling, especially in patients taking ACE inhibitors
🧠 Haemorrhagic transformation after ischaemic stroke thrombolysis

📚 References

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