Advanced Pharmacology · Topic 10 of 13

Thrombolytic Therapy

Pharmacology · fibrinolytics

Thrombolytic Therapy

Fibrinolytics dissolve fresh clot in STEMI without timely PCI, disabling ischemic stroke and high-risk PE — screen every patient for bleeding contraindications first.

Key numbers

STEMI: lyse if PCI > 120 mindoor → needle ≤ 30 min

Stroke: tenecteplase 0.25 mg/kg, max 25 mg0.25 mg/kg, max 25 mg

PE: alteplase 100 mg over 2 h100 mg over 2 h

Stroke lytics: BP < 185/110, then < 180/105< 185/110 mmHg

01 · GiveStroke: tenecteplase 0.25 mg/kg, max 25 mg

For disabling ischemic stroke within 4.5 hours of last known well, give tenecteplase 0.25 mg/kg bolus (max 25 mg) or alteplase 0.9 mg/kg (max 90 mg; 10% bolus, rest over 60 minutes).

02 · DoSTEMI: lyse if PCI > 120 min

In STEMI, give a fibrinolytic (usually tenecteplase) when PCI cannot happen within 120 minutes of first medical contact and symptoms began within 12 hours — door-to-needle goal 30 minutes.

03 · GivePE: alteplase 100 mg over 2 h

For high-risk PE (SBP < 90 mmHg or a fall of ≥ 40 mmHg for 15 minutes, or vasopressor need), give systemic alteplase 100 mg IV over 2 hours unless contraindicated.

What it is

Core idea

Plasminogen activators turn plasminogen into plasminFibrinolytics are plasminogen activators: they convert plasminogen to plasmin, which lyses fibrin. Tenecteplase is a fibrin-binding modified tPA with a longer half-life (20–24 minutes initially vs about 6 for alteplase), allowing a single bolus.

Diagnosis & monitoring

Work-up

Stroke lytics: BP < 185/110, then < 180/105 must knowBefore stroke thrombolysis lower BP below 185/110 mmHg and keep it below 180/105 for 24 hours afterward; give no antiplatelet or anticoagulant for 24 hours after thrombolysis.

Management

Orders

STEMI tenecteplase: 30–50 mg by weightSTEMI tenecteplase is one 5-second bolus by weight: 30 mg under 60 kg, rising 5 mg per 10-kg band to 50 mg at 90 kg or more; reteplase is a double bolus 30 minutes apart.

Lytic adjuncts: aspirin, clopidogrel, enoxaparinWith STEMI fibrinolysis give aspirin, clopidogrel (300 mg load under 75; 75 mg, no load, at 75+) and enoxaparin 30 mg IV plus 1 mg/kg every 12 hours (0.75 mg/kg, no bolus, at 75+).

Rescue PCI if lysis fails at 60 minutesAfter STEMI fibrinolysis, transfer every patient for angiography within 2–24 hours; if chest pain or ST elevation persists 60 minutes after the lytic, or shock develops, do rescue PCI immediately.

Red flags & don'ts

Avoid harm

Absolute bars: intracranial bleed, dissection, active bleeding avoidAbsolute contraindications (STEMI list): prior intracranial hemorrhage, cerebrovascular malformation or malignant intracranial tumor, ischemic stroke within 3 months, suspected aortic dissection, active bleeding, intracranial/spinal surgery within 2 months, head or facial trauma within 3 months.

Relative bars: BP > 180/110, anticoagulant, pregnancy avoidRelative contraindications: BP > 180/110 on presentation, ischemic stroke over 3 months ago, oral anticoagulant, pregnancy, active peptic ulcer, traumatic or prolonged CPR, major surgery within 3 weeks, internal bleeding within 2–4 weeks.

Stroke lytics: check glucose, platelets, INR avoidBefore stroke thrombolysis, CT must exclude hemorrhage and glucose must exceed 50 mg/dL; classic exclusions include platelets < 100,000/mcL, INR > 1.7 and a DOAC within 48 hours (now case by case).

No lytics for mild non-disabling stroke avoidDo not give thrombolysis for a mild non-disabling deficit (for example, isolated sensory loss) — dual antiplatelet therapy is preferred; a disabling deficit gets lytics regardless of NIHSS.

No fibrinolytics in NSTE-ACS avoidFibrinolytics benefit only STEMI; in unstable angina and NSTEMI they worsen outcomes, so reperfusion is by PCI or CABG.

Neuro decline after lytics: stop, scan, cryoprecipitate complicationNeurologic decline during or after thrombolysis: stop the infusion, get a STAT noncontrast head CT and fibrinogen; for symptomatic hemorrhage give cryoprecipitate 10 units (target fibrinogen ≥ 150 mg/dL), or tranexamic or aminocaproic acid.

Orolingual angioedema, worse with ACE inhibitors complicationAngioedema can occur during and up to 2 hours after alteplase, often in patients on ACE inhibitors; stop the infusion and treat with antihistamines, IV corticosteroids and epinephrine as needed.

The rules

Know these

No routine lysis for intermediate-risk PENormotensive PE with RV dysfunction or raised biomarkers is anticoagulated and monitored — routine systemic thrombolysis is not recommended (bleeding harm); catheter-directed therapy is used if lysis is contraindicated or fails.

Alteplase or tenecteplase?

Commonly confused

How given	Bolus plus infusion
Stroke dose	0.9 mg/kg (max 90 mg): 10% bolus, rest over 60 min
STEMI dose	Weight-based accelerated infusion, max 100 mg
Half-life	About 6 minutes
PE (high risk)	100 mg over 2 hours

More detail

Reference

Show 7 reference facts

Accelerated alteplase for STEMI: 15 mg bolus, then 0.75 mg/kg over 30 minutes (max 50 mg), then 0.5 mg/kg over 60 minutes (max 35 mg) — never more than 100 mg in total.

After alteplase for PE, start or resume heparin near the end of the infusion, once the aPTT or thrombin time has returned to twice normal or less.

When a stroke patient qualifies for both, give IV thrombolysis and proceed to thrombectomy — do not skip lytics for thrombectomy alone.

Catheter-directed thrombolysis is reserved for limb-threatening DVT (phlegmasia cerulea dolens) or selected younger patients with extensive iliofemoral DVT; bleeding is most often at puncture sites and is treated with compression.

Life-threatening bleeding during fibrinolysis is treated by stopping the drug and giving cryoprecipitate and fresh frozen plasma.

Obstructive left-sided mechanical valve thrombosis can be treated with low-dose, slow-infusion fibrinolysis or emergency surgery (both Class 1 in the 2020 ACC/AHA valve guideline).

Fibrinolytics can cause cholesterol embolization and reperfusion arrhythmias; keep antiarrhythmic therapy for bradycardia and ventricular irritability available.

Pearl

Three doses to own: tenecteplase 0.25 mg/kg (max 25 mg) for stroke, alteplase 0.9 mg/kg (max 90 mg) for stroke, alteplase 100 mg over 2 hours for PE.

Sources · Merck Manual Professional — Medications for Acute Coronary Syndromes (fibrinolytics; IV Fibrinolytic Therapies table) · Merck Manual Professional — Overview of Revascularization for Acute Coronary Syndromes (table: Contraindications to Fibrinolytic Therapy for STEMI) · TNKase (tenecteplase) prescribing information, revised 02/2025 (adds acute ischemic stroke) — DailyMed · Activase (alteplase) prescribing information — DailyMed · Rao SV et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes. Circulation 2025;151:e771–e862 · emDocs — 2026 Guideline Update: Early Management of Acute Ischemic Stroke (Jan 2026) · Merck Manual Professional — Ischemic Stroke (updated Jan 2026) · Guideline Central — Feb 2026 AHA/ASA Early Management of AIS Guideline Spotlight (10 take-home messages) · Merck Manual Professional — Pulmonary Embolism (PE) · CHEST Physician — Navigating PE treatment: what the AHA/ACC guidelines recommend · CardioNerds — Decipher the Guidelines: 2025 ACC/AHA ACS Guideline (antithrombotics with fibrinolysis, sections 4.3.2 and 4.4) · Lovenox (enoxaparin sodium) prescribing information (STEMI dosing; ≥ 75 years) — DailyMed · Louisiana Emergency Response Network — Post-thrombolytic symptomatic intracranial hemorrhage reversal guideline · EB Medicine — Emergency Department Management of Postthrombolysis Intracranial Hemorrhage · Merck Manual Professional — Medications for Deep Venous Thrombosis (thrombolytic agents; bleeding) · Thrombolytic therapy for mechanical aortic valve thrombosis in pregnancy: case report. Eur Heart J Case Rep 2022 (quotes the 2020 ACC/AHA Class 1 recommendation) · Yaghi S et al. Treatment and outcome of hemorrhagic transformation after IV alteplase in acute ischemic stroke: AHA/ASA scientific statement. Stroke 2017;48:e343–e361 · Charbonnier G et al. Intracranial bleeding after reperfusion therapy in acute ischemic stroke. Front Neurol 2020 (Table 4 reproduces the 2017 AHA/ASA reversal suggestions: cryoprecipitate 10 U, fibrinogen ≥ 150 mg/dL; antifibrinolytics) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).