Thrombolytic Agents
Pharmacology of fibrinolytic drugs used to dissolve acute thrombi in STEMI, ischemic stroke, and pulmonary embolism.
## Overview
Thrombolytics (fibrinolytics) activate the conversion of plasminogen to plasmin, which degrades fibrin clots. They are used in acute ST-elevation myocardial infarction (STEMI) when primary PCI is unavailable, acute ischemic stroke within the treatment window, and massive pulmonary embolism with hemodynamic instability.
## Mechanism of Action
All thrombolytics convert plasminogen to plasmin. Plasmin is a serine protease that cleaves fibrin polymers in the thrombus, dissolving the clot. Agents differ in their fibrin specificity, meaning how selectively they activate plasminogen bound to fibrin versus circulating plasminogen. Higher fibrin specificity reduces systemic fibrinogenolysis and theoretically lowers bleeding risk.
## Available Agents
- **Alteplase (tPA)**: Recombinant tissue plasminogen activator. Fibrin-specific. Half-life approximately 4-5 minutes. Standard of care for acute ischemic stroke (0.9 mg/kg IV, max 90 mg). Used in STEMI as accelerated infusion over 90 minutes.
- **Tenecteplase (TNKase)**: Engineered tPA variant with longer half-life (20-24 minutes), allowing single IV bolus dosing. Higher fibrin specificity than alteplase. Increasingly studied for acute stroke (lower bleeding in some trials). Preferred for STEMI fibrinolysis due to dosing simplicity.
- **Reteplase**: Double-bolus dosing (two 10-unit boluses 30 minutes apart). Moderate fibrin specificity. Convenient for STEMI when facility logistics favor bolus dosing.
- **Streptokinase**: Derived from streptococci. Non-fibrin-specific, causing systemic plasminogen activation. Antigenic (can cause allergic reactions and is ineffective on re-exposure). Low cost makes it relevant in resource-limited settings.
## Time Windows
For STEMI, fibrinolysis is most effective within 3 hours of symptom onset, with benefit declining substantially after 12 hours. For ischemic stroke, alteplase is approved within 4.5 hours. Tenecteplase is under investigation for extended windows when combined with thrombectomy. For PE, there is no strict time window, but treatment is reserved for massive PE with hemodynamic compromise.
## Contraindications
Absolute contraindications include active internal bleeding, recent (within 3 months) hemorrhagic stroke, intracranial neoplasm, and known bleeding diathesis. Recent major surgery, severe uncontrolled hypertension, and current anticoagulation are relative contraindications requiring risk-benefit assessment.
## Bleeding Management
Major bleeding occurs in 5-10% of patients. Intracranial hemorrhage is the most feared complication (0.5-1% for STEMI, 6-7% for stroke). Cryoprecipitate (fibrinogen replacement), tranexamic acid, and aminocaproic acid can be used to manage bleeding.
## Key Takeaways
- Thrombolytics convert plasminogen to plasmin, dissolving fibrin clots
- Fibrin specificity varies: tenecteplase > alteplase > streptokinase
- Time to treatment is the strongest predictor of benefit
- Intracranial hemorrhage is the most serious complication