Fibrinolytics | Medication Reference

Bedside Snapshot

Fibrinolytics convert plasminogen to plasmin, which degrades fibrin and dissolves intravascular clots.
Major ED/ICU uses: acute ischemic stroke, ST-elevation myocardial infarction (STEMI) when PCI unavailable, and high-risk (massive) pulmonary embolism with hemodynamic compromise. Selected uses: catheter-directed thrombolysis for PE/DVT/line thrombosis, acute limb ischemia, and some mechanical valve thromboses.
Alteplase (tPA) is the workhorse for ischemic stroke and is also used for PE and (less commonly now) STEMI. Tenecteplase (TNK) is standard for STEMI in many systems and is increasingly used off-label for stroke. Reteplase and streptokinase are primarily legacy MI agents with decreasing use in many regions.
Systemic thrombolysis carries a significant risk of major bleeding and intracranial hemorrhage (ICH). Patient selection and strict contraindication screening are critical.
Time is critical: for stroke and STEMI, benefit is highest when given as early as possible after symptom onset. Delayed administration offers diminishing benefit and higher relative bleeding risk.
Fibrinolytics do not replace mechanical reperfusion (PCI, thrombectomy) but are important when definitive mechanical options are delayed or unavailable.

Brand & Generic Names

Generic Names: Alteplase (tPA), Tenecteplase (TNK-tPA), Reteplase (rPA), Streptokinase (SK)
Brand Names: Alteplase: Activase, Cathflo Activase; Tenecteplase: TNKase; Reteplase: Retavase; Streptokinase: Streptase (various)

Medication Class

Fibrinolytics / Thrombolytics – Plasminogen Activators (systemic and catheter-directed)

Pharmacology

Mechanism of Action:

All fibrinolytics act by converting plasminogen to plasmin, the active enzyme that degrades fibrin and fibrinogen, leading to clot breakdown (fibrinolysis)
Alteplase and tenecteplase are recombinant tissue plasminogen activators (tPA) with relative fibrin selectivity: they preferentially activate plasminogen bound to fibrin within a thrombus
Reteplase is a modified tPA variant with a longer half-life and less fibrin specificity than alteplase, allowing double-bolus dosing
Streptokinase is a bacterial protein that forms a complex with plasminogen to generate plasmin; it is non-fibrin–specific, often generates systemic fibrinolysis, and is immunogenic (antibody formation)
By promoting fibrinolysis, these agents can restore perfusion to ischemic tissue but also disrupt hemostatic plugs at other sites, causing systemic bleeding complications

Pharmacokinetics:

Alteplase (tPA): Initial half-life ~5 minutes (rapid clearance) with a terminal phase 30–60 minutes; requires bolus plus infusion for systemic indications
Tenecteplase (TNK-tPA): Longer half-life (~20–24 minutes) supports single-bolus administration; genetically modified tPA with greater fibrin specificity
Reteplase (rPA): tPA derivative with reduced fibrin specificity and longer half-life than alteplase; allows two small IV boluses 30 minutes apart
Streptokinase (SK): Non-enzymatic protein that forms complex with plasminogen; antibody formation after prior exposure can reduce efficacy and increase allergic reactions

Indications

Alteplase (tPA):

Acute ischemic stroke (primary indication)
STEMI when PCI is unavailable or delayed
Massive PE with hemodynamic compromise
Low-dose catheter-directed use for PE/DVT and catheter occlusion

Tenecteplase (TNK-tPA):

STEMI (approved widely; single IV bolus dosing)
Acute ischemic stroke (increasingly used off-label in some centers and guidelines)

Reteplase (rPA):

STEMI as a double-bolus regimen (not commonly used for stroke)

Streptokinase (SK):

Historically used widely for STEMI, PE, and DVT (use has declined due to antigenicity, hypotension, and higher bleeding rates)

Other Uses:

Catheter-directed thrombolysis for PE, DVT, or peripheral arterial thrombosis (lower doses delivered locally via catheter)
Acute limb ischemia (highly protocolized, managed by vascular surgery/interventional radiology)
Mechanical valve thrombosis (selected cases)

Dosing & Administration

Available Forms:

Alteplase: 50 mg and 100 mg vials (reconstituted for IV use); 2 mg vials (Cathflo Activase for catheter clearance)
Tenecteplase: 50 mg vial (reconstituted for single-bolus IV use)
Reteplase: 10.4 unit (10 mg) vials for IV bolus
Streptokinase: 250,000 unit, 750,000 unit, and 1.5 million unit vials for IV infusion

Systemic Fibrinolytic Dosing – Adult (ED/ICU; always follow local protocols):

Indication	Agent	Typical Dose	Administration	Notes
Acute ischemic stroke	Alteplase	0.9 mg/kg (max 90 mg)	10% IV bolus over 1 min, then 90% IV infusion over 60 min	Give within guideline-defined time window from last-known-well (e.g., up to 4.5 h in selected patients)
Acute ischemic stroke (off-label in many regions)	Tenecteplase	0.25 mg/kg (max 25 mg)	Single IV bolus over ~5–10 seconds	Used in some stroke systems instead of alteplase; dosing and indications are guideline- and institution-dependent
STEMI (when PCI unavailable)	Alteplase	Total 100 mg (≥67 kg)	15 mg IV bolus; then 0.75 mg/kg (max 50 mg) over 30 min; then 0.5 mg/kg (max 35 mg) over 60 min	Weight-adjusted regimens exist for <67 kg; give with aspirin and anticoagulation
STEMI (preferred bolus agent in many systems)	Tenecteplase	Weight-based: 30–50 mg	Single IV bolus: 30 mg (<60 kg), 35 mg (60–69 kg), 40 mg (70–79 kg), 45 mg (80–89 kg), 50 mg (≥90 kg)	Give with aspirin and anticoagulation; easiest STEMI regimen in out-of-hospital/ED settings
STEMI (legacy agent)	Reteplase	10 units IV ×2	10 units IV over 2 min, then 10 units again after 30 min	Give with aspirin and heparin; less commonly used in some regions
STEMI or PE (where streptokinase used)	Streptokinase	1.5 million units IV	Infused over 60 min	May cause hypotension and is immunogenic; largely replaced by newer agents

Pulmonary Embolism – Systemic Thrombolysis (Adult; examples):

Agent	Typical Dose	Administration	Notes
Alteplase (standard PE regimen)	100 mg IV total	Infusion over 2 hours	Common for massive PE with hypotension; some protocols use 0.6 mg/kg over 15 min
Alteplase (reduced-dose regimen)	50 mg IV	Infusion over 2 hours	Used in some intermediate-risk PE protocols or high bleed-risk patients; evidence evolving
Streptokinase	250,000 unit IV loading, then 100,000 units/h	Loading over 30 min, then infusion for 12–24 h	Less commonly used now; more systemic effects and hypotension

Catheter-Directed and Other Dosing Examples:

Alteplase for catheter-directed PE/DVT: Low-dose infusions (e.g., 0.5–1 mg/h per catheter, with maximum daily dose limits) per interventional and institutional protocols
Alteplase for central venous catheter occlusion: 2 mg in 2 mL instilled into the catheter lumen (dwell 30–120 min), repeat once if needed (adult dosing; pediatric volumes are smaller)
Acute limb ischemia: Fibrinolytic dosing is highly protocolized and usually managed by vascular surgery/interventional radiology

Contraindications

Absolute Contraindications (typical; always check local protocol):

Any prior intracranial hemorrhage
Known structural cerebral vascular lesion (e.g., AVM, aneurysm) or malignant intracranial neoplasm
Ischemic stroke within the last 3 months (except acute ischemic stroke being treated with tPA under stroke protocols)
Suspected aortic dissection
Active internal bleeding (excluding menses)
Significant closed-head or facial trauma within 3 months
Intracranial or intraspinal surgery within recent weeks (timeframes vary by guideline)

Relative Contraindications:

Severe uncontrolled hypertension (e.g., SBP >180–185 mmHg or DBP >110–115 mmHg) despite antihypertensive therapy
Recent major surgery (<2–3 weeks), recent internal bleeding, or traumatic/prolonged CPR
History of ischemic stroke beyond guideline exclusion periods, dementia, or other intracranial pathology increasing bleeding risk
Pregnancy, active peptic ulcer disease, or current use of anticoagulants with elevated INR or low fibrinogen
Advanced age and frailty – not absolute, but bleeding risk is higher; requires individualized risk–benefit discussion

Critical Warning: Systemic fibrinolysis carries a significant risk of major bleeding and intracranial hemorrhage. Patient selection and strict contraindication screening are critical. Always follow institutional protocols and time windows.

Adverse Effects

Common (Class):

Minor bleeding: gingival bleeding, ecchymoses, oozing from IV sites
Hypotension, particularly with streptokinase and rapid infusions
Nausea, vomiting

Serious:

Intracranial hemorrhage (ICH): Most feared complication; risk varies with indication, age, blood pressure, and comorbidities
Major systemic bleeding: Requiring transfusion or procedural intervention (GI bleed, retroperitoneal hemorrhage, hemopericardium)
Reperfusion arrhythmias: Accelerated idioventricular rhythm, VT/VF after successful coronary thrombolysis
Allergic reactions and anaphylaxis: Particularly with streptokinase (immunogenic)
Orolingual angioedema: With alteplase in stroke patients, especially those on ACE inhibitors

Hemorrhage Risk: The risk of intracranial hemorrhage is 2–7% with stroke thrombolysis and 0.5–1% with STEMI thrombolysis. Close monitoring and blood pressure control are essential.

Special Populations

Elderly:

Advanced age increases bleeding risk, particularly intracranial hemorrhage
Not an absolute contraindication but requires careful risk–benefit assessment
Stroke guidelines include age-related considerations in extended time windows

Renal Impairment:

No specific dose adjustments for alteplase, tenecteplase, or reteplase
Renal dysfunction may increase bleeding risk; assess overall patient risk profile

Hepatic Impairment:

Severe hepatic dysfunction increases bleeding risk due to coagulopathy
May be a relative contraindication depending on coagulation parameters

Pregnancy & Lactation:

Pregnancy is a relative contraindication for systemic fibrinolysis
Use only when potential benefit justifies the risk (e.g., life-threatening PE, STEMI)
Limited data on excretion in breast milk; benefits vs. risks should be discussed

Weight-Based Considerations:

Tenecteplase and stroke-dose alteplase are weight-based with maximum dose caps
Ensure accurate weight measurement for proper dosing

Monitoring

Neurologic Monitoring:

Frequent neurologic checks (q15–30 min initially) after stroke thrombolysis to detect early signs of intracranial hemorrhage
Immediate head CT if sudden neurologic deterioration, severe headache, or new focal deficits occur

Cardiovascular Monitoring:

Continuous ECG and serial hemodynamics for STEMI and PE patients to assess reperfusion and detect arrhythmias or hypotension
Monitor for reperfusion arrhythmias (common after successful STEMI thrombolysis)

Blood Pressure Control:

Strict blood pressure control per indication-specific protocols (e.g., <180/105 mmHg for stroke post-tPA, or as per local guidelines)
Antihypertensives may be needed to maintain target ranges

Laboratory Monitoring:

Serial hemoglobin/hematocrit, fibrinogen, and coagulation parameters in patients at high risk of bleeding or receiving prolonged infusions
Type and screen/crossmatch blood products in case transfusion is needed

Bleeding Surveillance:

Site checks for bleeding: IV lines, arterial lines, Foley catheter, surgical sites
Monitor for occult bleeding: abdominal exam, back/flank tenderness, stool guaiac, NG tube aspirate
Assess for signs of retroperitoneal or intra-abdominal bleeding

Clinical Pearls

Mechanical vs. Pharmacologic Reperfusion: When considering systemic fibrinolysis, always ask: "Is there a mechanical option?" For stroke (thrombectomy) and MI (PCI), mechanical reperfusion is usually preferred when rapidly available.

Stroke Details Matter: For acute ischemic stroke, precise last-known-well time, blood pressure control, imaging findings, and contraindication screening should be standardized with checklists or stroke-team protocols.

Tenecteplase Advantages: Tenecteplase's single-bolus dosing makes it very attractive for prehospital or small-hospital STEMI systems. For stroke, follow your regional stroke guideline regarding whether to use alteplase or TNK.

STEMI Post-Thrombolysis Care: After fibrinolysis for STEMI, early transfer to a PCI-capable center for rescue or routine angiography is standard. Watch for reperfusion arrhythmias as a marker of successful reperfusion.

Massive PE Management: In massive PE with shock, systemic alteplase can be life-saving. In higher bleeding-risk patients or submassive PE, consider catheter-directed approaches and multidisciplinary PE team input.

Time = Tissue: For stroke and STEMI, benefit is highest when fibrinolytics are given as early as possible after symptom onset. Delayed administration offers diminishing benefit and higher relative bleeding risk.

Bleeding Management: If serious bleeding occurs during thrombolysis, stop the infusion immediately. Consider cryoprecipitate (to replace fibrinogen), fresh frozen plasma, tranexamic acid, and consultation with hematology. For ICH, obtain emergent neurosurgical consultation.

References

1. Powers, W. J., Rabinstein, A. A., Ackerson, T., et al. (2019). 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the AHA/ASA. Stroke, 50(12), e344–e418.
2. O'Gara, P. T., Kushner, F. G., Ascheim, D. D., et al. (2013). 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction. Circulation, 127(4), e362–e425.
3. Konstantinides, S. V., Meyer, G., Becattini, C., et al. (2019). 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism. European Heart Journal, 41(4), 543–603.
4. Lexicomp. (2024). Alteplase, tenecteplase, reteplase, and streptokinase: Drug information. Wolters Kluwer.
5. EMCrit Project. (2023–2024). Pulmonary embolism (IBCC), Acute coronary syndrome (IBCC), and Stroke (IBCC). https://emcrit.org/