D.K was given alteplase in the emergency department while suffering from an acute myocardial infarction.
D.K inquiries about why this drug was given. Explain why alteplase is given and how it works? (USLO 5.2, 5.3, 5.4)
Explain some of the main concerns with the administration of thrombolytics. (USLO 5.3, 5.5, 5.6, 5.8)
Explain the differences between the mechanism of action of alteplase, aspirin and clopidogrel. What are the indications of aspirin and clopidogrel?
Case Context
Patient: D.K
Condition: Acute Myocardial Infarction (AMI)
Intervention: Administration of alteplase in the emergency department
1. Why Alteplase Was Given and How It Works (USLO 5.2, 5.3, 5.4)
Purpose of Alteplase in AMI:
Alteplase is a thrombolytic (fibrinolytic) agent used to dissolve blood clots that obstruct coronary arteries during an acute myocardial infarction.
The goal is to restore blood flow (reperfusion) to the ischemic myocardium, limit infarct size, and improve survival.
Mechanism of Action:
Alteplase is a recombinant tissue plasminogen activator (tPA).
It binds to fibrin in a thrombus and converts plasminogen → plasmin.
Plasmin is an enzyme that breaks down fibrin, the structural protein of clots.
This leads to clot dissolution and reopening of the blocked coronary artery.
Clinical Rationale:
In AMI, rapid reperfusion is critical.
Alteplase is given when percutaneous coronary intervention (PCI) is not immediately available or as part of early reperfusion therapy.
2. Main Concerns with Administration of Thrombolytics (USLO 5.3, 5.5, 5.6, 5.8)
Risk of Bleeding:
Major adverse effect is hemorrhage, especially intracranial hemorrhage.
Contraindications include recent surgery, trauma, stroke, or active bleeding.
Timing of Administration:
Most effective when given within 12 hours of symptom onset, ideally within 30 minutes of hospital arrival.
Delayed administration reduces benefit and increases risk.
Reperfusion Arrhythmias:
Restoration of blood flow can trigger arrhythmias (e.g., ventricular tachycardia).
Allergic Reactions:
Rare, but hypersensitivity can occur.
Monitoring Requirements:
Continuous cardiac monitoring.
Frequent neurological checks for signs of intracranial bleeding.
Monitoring of coagulation parameters.
3. Differences in Mechanism of Action: Alteplase vs. Aspirin vs. Clopidogrel
Drug Mechanism of Action Primary Effect Indications
Alteplase Converts plasminogen → plasmin; dissolves fibrin clots Breaks down existing thrombus Acute MI, ischemic stroke, massive PE
Aspirin Irreversibly inhibits cyclooxygenase (COX-1/COX-2) → ↓ thromboxane A2 Prevents platelet aggregation Secondary prevention of MI, stroke, unstable angina, post-PCI
Clopidogrel Irreversibly blocks P2Y12 ADP receptor on platelets Prevents platelet activation and aggregation Prevention of stent thrombosis, ACS, secondary prevention of MI/stroke
Key Differences
Alteplase: Dissolves existing clots (fibrinolysis).
Aspirin & Clopidogrel: Prevent formation of new clots (antiplatelet agents).
Combination Therapy: Often used together—alteplase for acute reperfusion, aspirin/clopidogrel for long-term prevention.
4. Indications of Aspirin and Clopidogrel
Aspirin:
Acute management of MI and unstable angina.
Long-term secondary prevention of cardiovascular events (MI, stroke).
Used in patients with established atherosclerotic cardiovascular disease.
Clopidogrel:
Acute coronary syndrome (ACS).
Prevention of stent thrombosis after PCI.
Secondary prevention of ischemic stroke and peripheral arterial disease.
Often used in combination with aspirin (“dual antiplatelet therapy”).
Summary
Alteplase was given to D.K to rapidly dissolve the clot causing the myocardial infarction.
Main concerns include bleeding risk, timing, reperfusion arrhythmias, and need for close monitoring.
Mechanistic differences:
Alteplase dissolves clots (fibrinolysis).
Aspirin and clopidogrel prevent platelet aggregation (antiplatelet).
Indications: Aspirin and clopidogrel are used for prevention of future cardiovascular events, while alteplase is used acutely to restore perfusion.
