Fibrinolytic agents, also known as thrombolytics, are medications used to dissolve blood clots. They are primarily used in the management of acute thrombotic conditions such as myocardial infarction (heart attack), pulmonary embolism, and ischemic stroke.
Mechanism of Action
Fibrinolytic agents work by converting plasminogen to plasmin, an enzyme that breaks down fibrin, the main component of blood clots. This process, called fibrinolysis, helps to dissolve the clot and restore normal blood flow.
Types of Fibrinolytic Agents
- Tissue Plasminogen Activator (tPA)
- Streptokinase
- Urokinase
- Tenecteplase
- Reteplase
1. Tissue Plasminogen Activator (tPA)
Examples: Alteplase
- Mechanism: tPA binds to fibrin in a clot and converts entrapped plasminogen to plasmin, initiating local fibrinolysis.
- Uses: Acute myocardial infarction, acute ischemic stroke, pulmonary embolism.
- Dosage:
- Acute Myocardial Infarction: 15 mg IV bolus, followed by 0.75 mg/kg (up to 50 mg) IV over 30 minutes, then 0.5 mg/kg (up to 35 mg) IV over 60 minutes.
- Acute Ischemic Stroke: 0.9 mg/kg (maximum 90 mg), with 10% of the total dose given as an initial IV bolus and the remainder infused over 60 minutes.
- Adverse Effects: Bleeding, particularly intracranial hemorrhage, allergic reactions, hypotension.
- Contraindications: Active internal bleeding, history of recent stroke, severe uncontrolled hypertension, recent surgery, or trauma.
2. Streptokinase
Mechanism: Activates plasminogen to plasmin by forming a complex that cleaves plasminogen, leading to systemic fibrinolysis.
- Uses: Acute myocardial infarction, pulmonary embolism, deep vein thrombosis.
- Dosage:
- Acute Myocardial Infarction: 1.5 million units IV over 60 minutes.
- Adverse Effects: Bleeding, hypotension, allergic reactions, including anaphylaxis.
- Contraindications: Previous streptokinase treatment (within 6 months to 1 year), active internal bleeding, recent stroke, recent surgery, or trauma.
3. Urokinase
Mechanism: Directly converts plasminogen to plasmin, leading to fibrinolysis.
- Uses: Pulmonary embolism, deep vein thrombosis, catheter clearance.
- Dosage:
- Pulmonary Embolism: 4400 IU/kg IV bolus over 10 minutes, followed by 4400 IU/kg/hour for 12 hours.
- Adverse Effects: Bleeding, fever, allergic reactions.
- Contraindications: Active internal bleeding, recent stroke, recent surgery or trauma.
4. Tenecteplase
Mechanism: A genetically engineered variant of tPA with a longer half-life, allowing for single bolus administration.
- Uses: Acute myocardial infarction.
- Dosage:
- Acute Myocardial Infarction: Weight-based dosing: <60 kg: 30 mg, 60-70 kg: 35 mg, 70-80 kg: 40 mg, 80-90 kg: 45 mg, >90 kg: 50 mg, all given as a single IV bolus.
- Adverse Effects: Bleeding, including intracranial hemorrhage, allergic reactions.
- Contraindications: Active internal bleeding, history of a recent stroke, severe uncontrolled hypertension, recent surgery or trauma.
5. Reteplase
Mechanism: A recombinant plasminogen activator similar to tPA but with a longer half-life.
- Uses: Acute myocardial infarction.
- Dosage:
- Acute Myocardial Infarction: 10 units IV bolus, followed by a second 10 units IV bolus 30 minutes later.
- Adverse Effects: Bleeding, including intracranial hemorrhage, allergic reactions.
- Contraindications: Active internal bleeding, history of a recent stroke, severe uncontrolled hypertension, recent surgery, or trauma.
Clinical Guidelines and Monitoring
In the UK, the use of fibrinolytic agents is guided by clinical guidelines from bodies such as the National Institute for Health and Care Excellence (NICE) and the British Heart Foundation (BHF).
- Acute Myocardial Infarction:
- Fibrinolytic therapy should be administered as soon as possible, ideally within 12 hours of symptom onset, if primary percutaneous coronary intervention (PCI) is not available.
- tPA (Alteplase), Streptokinase, and Tenecteplase are commonly used.
- Acute Ischemic Stroke:
- tPA (Alteplase) should be administered within 4.5 hours of symptom onset after excluding intracranial hemorrhage via imaging.
- Pulmonary Embolism:
- Fibrinolytic therapy is indicated for massive PE with hemodynamic instability.
Monitoring and Adverse Effects
Regular monitoring is crucial to ensure the safety and efficacy of fibrinolytic therapy:
- Vital Signs: Continuous monitoring of blood pressure, heart rate, and oxygen saturation.
- Neurological Status: Frequent assessments for signs of intracranial hemorrhage.
- Bleeding Complications: Regular assessments for signs of bleeding, both overt and occult.
- Laboratory Tests: Complete blood count (CBC), coagulation profile (INR, aPTT), and fibrinogen levels.