Thrombolytic

Alteplase (Activase)

Also called tPA, Activase

Reviewed by Alex G, BSN, RN, CEN, CCRN, CMC, NREMT-P · From the Reference tab of the app

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)

On the quick cards

Thrombolytics (-teplase)NCLEX Drug Classes: Acute ischemic stroke, MI, massive PE

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

Safety

Symptomatic intracranial hemorrhage in about 6% after stroke lysis (6.4% in NINDS); headache, vomiting, rising BP or a worse exam: stop it, emergency CT
Orolingual angioedema in about 1–5%, more with ACE inhibitors, up to 2 h after the infusion, often opposite the infarct: stop the drug, protect the airway
Contraindicated with active bleeding, intracranial hemorrhage, recent intracranial or spinal surgery or head trauma, bleeding diathesis or severe uncontrolled hypertension (label)
After stroke lysis: BP below 180/105 for 24 h; no antithrombotics until 24-h imaging; delay NG tubes, urinary catheters and arterial lines
Cholesterol embolization and re-embolization from a lysed DVT (label)
No antidote: for symptomatic bleeding, cryoprecipitate to fibrinogen 150 mg/dL or more plus tranexamic acid 1 g IV (AHA/ASA)

In the one-pagers

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 Shock Types at a Glance questions free16 exam-style questions with rationales on the topic where Alteplase comes up most. No account or download needed.

In the algorithms

Stroke Code

Tenecteplase

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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 the order, the label and your institution's protocols.