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ICU Medication MasterclassAlteplase • Tenecteplase • Stroke • PE • STEMI • Bleeding

Thrombolysis & Reperfusion Pharmacology

A high-risk medication framework for alteplase and tenecteplase across acute ischemic stroke and other reperfusion syndromes. The same fibrinolytic mechanism does not mean the same indication, dose or contraindication set.

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1

Separate stroke thrombolysis from PE/STEMI fibrinolysis indications and dosing.

2

Know that 2026 AHA/ASA stroke guidance endorses either alteplase or tenecteplase within the standard 4.5-hour window for eligible disabling AIS.

3

Prioritize hemorrhage contraindications, blood-pressure control and exact weight-based dosing before administration.

4

Recognize that non-disabling minor stroke is not automatically a thrombolysis indication.

5

Link thrombolysis decisions to thrombectomy/catheter/surgical options rather than treating lysis as the only reperfusion tool.

Acute Ischemic Stroke

Full stroke selection, imaging and thrombectomy pathway.

Open →

Pulmonary Embolism

High-risk PE shock and reperfusion strategy.

Open →

Bleeding & Reversal

Hemorrhage response and reversal principles.

Open →
Core agents

Choose by physiology, not by habit

The table below is a selection framework. Open the individual monograph for exact dosing, preparation, renal/CRRT/IHD adjustment, interactions and evidence traceability.

Alteplase
Thrombolytic / Recombinant Tissue Plasminogen Activator
Core agent

ICU role: Recombinant tPA used for eligible AIS and selected thrombolytic indications with syndrome-specific dosing.

Choose: Evidence-based IV thrombolytic option for eligible disabling AIS within the treatment window and in selected extended-window imaging-defined patients.
Hesitate: Intracranial/systemic bleeding, strict syndrome-specific dosing and contraindication review.

Monitor: Neurologic status, BP, bleeding and post-lysis imaging/protocol.

Tenecteplase
Fibrinolytic
Core agent

ICU role: Modified fibrinolytic with bolus administration and current stroke evidence supporting use in eligible patients.

Choose: 2026 AHA/ASA permits tenecteplase or alteplase within 4.5 hours for eligible disabling AIS; tenecteplase also has established STEMI use with different dosing.
Hesitate: Do not transfer one indication's dose to another; major bleeding remains the key hazard.

Monitor: Weight-based dose verification, BP, neurologic status and hemorrhage.

Clinical decision matrix

What changes the drug choice?

Disabling AIS within 4.5 hours

Preferred reasoning: Use either alteplase or tenecteplase if the patient is otherwise eligible, without delaying treatment for unnecessary advanced imaging.
Avoid: Withholding solely because NIHSS is numerically low when the deficit is disabling.

Why: 2026 AHA/ASA emphasizes disabling deficit and rapid eligible thrombolysis.

Non-disabling minor AIS

Preferred reasoning: Use the guideline-directed antiplatelet strategy when appropriate rather than routine IV thrombolysis.
Avoid: Treating every low-NIHSS stroke with lysis.

Why: Trials have not shown benefit for non-disabling deficits in the standard window.

Massive PE with shock

Preferred reasoning: Choose systemic thrombolysis only when the PE risk/contraindication profile supports it and catheter/surgical options are considered.
Avoid: Using the stroke dose of alteplase or tenecteplase for PE.

Why: Indication-specific regimens and bleeding risks differ.

Recent major surgery

Preferred reasoning: Perform a structured contraindication/bleeding-risk assessment and consider non-lytic reperfusion alternatives when feasible.
Avoid: Treating 'life-threatening thrombosis' as an automatic waiver of bleeding risk.

Why: Reperfusion strategy must match both thrombosis severity and bleeding hazard.

High-yield protocols

Mechanism-based sequences worth memorizing

Before IV stroke thrombolysis

  1. Confirm last-known-well / imaging eligibility and that the deficit is disabling.
  2. Check BP and major hemorrhage contraindications, anticoagulant exposure and glucose mimic.
  3. Verify exact weight-based drug/dose, then treat without avoidable delay.
⚠️ Alteplase and tenecteplase are not dose-interchangeable across indications.
Organ failure & special settings

When standard pharmacology stops being standard

Anticoagulated patient
Priority: Verify agent, timing and relevant coagulation parameters before lysis.
Pitfall: Assuming all DOAC/warfarin exposure is equivalent.
Post-thrombolysis deterioration
Priority: Stop infusion if applicable, urgent imaging/labs, and activate hemorrhage management.
Pitfall: Attributing new headache/hypertension/decline to the stroke without excluding ICH.
Thrombectomy candidate
Priority: Do not delay eligible IV thrombolysis while arranging EVT when the guideline supports both.
Pitfall: Treating EVT and IVT as mutually exclusive by default.
Resident progression

R1 → R5 bedside cases

Recognition becomes selection, then organ-failure adjustment, competing physiology and senior-level prioritization.

R1

Standard-window disabling stroke

Aphasia and right arm weakness 90 minutes from onset, no bleeding contraindication.

Show reasoning

Proceed rapidly with eligible IV thrombolysis; 2026 AHA/ASA endorses either alteplase or tenecteplase within 4.5 hours.

R2

Minor non-disabling deficit

Isolated mild sensory loss, NIHSS 1, within 2 hours.

Show reasoning

Do not equate time-window eligibility with benefit; non-disabling minor stroke is generally managed with antiplatelet therapy rather than routine IVT.

R3

DOAC exposure

Disabling stroke, apixaban taken recently, renal function reduced.

Show reasoning

Do not give lysis reflexively; assess timing, renal clearance and guideline-defined anticoagulant eligibility before choosing IVT or EVT-only strategy.

R4

Shock from PE

Massive PE with profound shock but recent abdominal surgery.

Show reasoning

Balance immediate mortality risk against major surgical bleeding and assess catheter/surgical reperfusion; systemic lysis is not automatic.

R5

Worsening after lysis

Twenty minutes after thrombolysis the patient develops vomiting, severe headache and neurologic decline.

Show reasoning

Treat as possible symptomatic ICH: stop drug if still infusing, urgent CT/labs and activate hemorrhage-reversal/support pathway.

Full medication monograph

Alteplase

Recombinant human tissue-type plasminogen activator (rt-PA) that binds fibrin and converts clot-bound plasminogen into active plasmin, causing targeted enzymatic fibrinolysis for massive PE, acute ischemic stroke, and catheter cl…

Dosing • renal/CRRT • toxicity • interactions →
Full medication monograph

Tenecteplase

Fibrin-specific thrombolytic used for STEMI and acute ischemic stroke. The 2026 AHA/ASA guideline recommends tenecteplase 0.25 mg/kg (max 25 mg) or alteplase for eligible AIS within 4.5 hours; regulatory labeling may be narrower …

Dosing • renal/CRRT • toxicity • interactions →

Evidence & bedside-use boundary

This Masterclass teaches selection and reasoning. Exact dosing, concentration, infusion preparation, renal/hepatic/RRT adjustment and monitoring must be checked in the linked medication monograph and the institution's current formulary/protocol. Local resistance patterns and regulatory drug availability can change faster than a static teaching page.

2026 AHA/ASA Guideline for Early Management of Acute Ischemic Stroke
Current thrombolysis window and alteplase/tenecteplase framework.