Thrombolytic
Alteplase (Activase)
Also called tPA, Activase
Indications
- Acute ischemic stroke within 3 h (label), or to 4.5 h per AHA/ASA (off-label beyond 3 h)
- Massive pulmonary embolism (label)
- STEMI without timely PCI (label)
- Occluded central venous catheters (Cathflo Activase)
- Stroke at 4.5–9 h or on waking with perfusion or MRI mismatch (off-label; AHA/ASA 2026)
- Cardiac arrest from suspected pulmonary embolism (off-label)
- Intrapleural, with dornase alfa, for pleural infection (off-label)
Mechanism of action
Alteplase is recombinant human tissue plasminogen activator (tPA), a serine protease. Its finger and kringle 2 domains bind fibrin, and on the clot it cleaves plasminogen at Arg561–Val562 to form plasmin, which splits fibrin into soluble fragments such as D-dimer. Fibrin binding lowers its Km for plasminogen about 400-fold (Hoylaerts 1982), so activation concentrates on the clot, though therapeutic doses also activate some circulating plasminogen. PAI-1 (plasminogen activator inhibitor-1) inactivates it in plasma, and α2-antiplasmin neutralizes free plasmin.
Pharmacology
- Hematologic: lyses fresh fibrin-rich thrombus and hemostatic plugs alike; fibrinogen falls 16–36% after 100 mg (label)
- CNS: NINDS patients were at least 30% more likely to have minimal or no disability at 3 months
- Cardiovascular: TIMI 3 flow at 90 min in 54% of STEMI patients on the accelerated regimen (GUSTO-I); reperfusion arrhythmias
- Other: plasmin activates kinin and complement pathways; bradykinin, normally broken down by ACE, drives orolingual angioedema
Pharmacokinetics
| Onset | Minutes after the IV bolus |
|---|---|
| Duration | Brief in plasma; the lytic state and bleeding risk last longer |
| Half-life | Initial under 5 min (label); terminal about 72 min (StatPearls) |
| Distribution | Initial Vd about plasma volume (label) |
| Protein binding | Inactivated by complexing with PAI-1 |
| Metabolism | Hepatic uptake by LRP1 and mannose receptors, then breakdown to amino acids |
| Clearance | 380–570 mL/min, mostly hepatic (label); hence bolus plus infusion |
Chemistry
- Recombinant human tPA from CHO cells: a 527-amino acid glycoprotein, about 59 kDa (65 kDa with its sugars)
- Finger and kringle 2 domains bind fibrin; a high-mannose sugar on kringle 1 (Asn117) helps the liver clear it
- Lyophilized with L-arginine (solubilizer), phosphoric acid and polysorbate 80; 1 mg/mL in sterile water, pH about 7.3, no preservative
- Swirl, never shake (foaming degrades it); use within 8 h; dilute only with NS or D5W, no other drug in the line (label)
Adverse effects and cautions
In the one-pagers
- Pulmonary EmbolismAnticoagulation: Alteplase: hold heparin, restart at aPTT ≤2× normal (US label); ESC 2019 lets UFH run
- Neuro: ICP and StrokeAcute ischemic stroke: Alteplase: 0–4.5 h: 0.9 mg/kg (max 90): 10% bolus, rest over 1 h
- ACS and STEMIReperfusion: timelines and strategy: Each 30 min of delay to primary PCI raised the relative risk of death at 1 year by 7.5% (De Luca 2004). Goals run from first medical contact: device ≤90 min at a PCI center, ≤120 min with transfer, and door-in-door-out ≤30 min (AHA Mission: Lifeline). Primary PCI restores TIMI 3 flow in over 90%, against 54% with accelerated alteplase in GUSTO-I, with less intr
- Aortic Dissection and Hypertensive EmergencyRecognition: ADD-RS, D-dimer and imaging: Inferior STEMI or stroke with back pain, a pulse deficit or a new diastolic murmur is dissection until imaging says otherwise: heparin, antiplatelets and lytics can be fatal, and the 2019 AHA/ASA stroke guideline calls alteplase harmful in suspected arch dissection.
- Chest Tubes and PneumothoraxHemothorax, effusions and pleural infection: Instil alteplase 10 mg in 30 mL saline, then DNase 5 mg in 30 mL, then a saline flush; close the drain for 1 hour; repeat twice daily for 3 days (BTS 2023).
- Shock Types at a GlanceObstructive shock: PE, tamponade, tension pneumothorax: Massive PE: a sudden rise in PVR dilates the thin RV, which cannot generate a mean PA pressure much above 40 mm Hg acutely; the septum bows into the LV and RV ischemia spirals into arrest. ESC 2019 high-risk PE is SBP <90 for ≥15 min, pressor need or arrest. Echo shows RV:LV >1, a D-shaped septum and McConnell sign. Give alteplase 100 m
Practice Pulmonary Embolism questions free8 exam-style questions with rationales on the topic where Alteplase comes up most. No account or download needed.
In the algorithms
Other thrombolytic drugs
Practice free in your browser2,450+ exam-style questions with rationales. No account, no ads. Also free on the App Store and Google Play.
Sources
- FDA label: Activase (2022)
- StatPearls: Alteplase (2023)
- Hoylaerts 1982 (fibrin kinetics)
- AHA/ASA acute ischemic stroke guideline (2026)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.