Thrombolytic Agents and Contraindications
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Direct answer
Thrombolytic agents are drugs that lyse the fibrin clot occluding an artery, most often a coronary artery in STEMI or a cerebral artery in ischaemic stroke. Streptokinase is cheap but non-fibrin specific and antigenic, while alteplase and tenecteplase are fibrin specific. Any past intracranial haemorrhage, active internal bleeding or suspected aortic dissection is an absolute contraindication.
What you must remember
- Streptokinase: a streptococcal protein that is non-fibrin specific and cheap, with hypotension and allergic reactions as typical problems.
- Alteplase: recombinant tissue plasminogen activator, fibrin specific, and the usual agent for acute ischaemic stroke in eligible patients.
- Tenecteplase: a modified alteplase given as a single weight-based bolus, fibrin specific, and practical for pre-hospital use.
- Repeat streptokinase: avoided, because antibodies from the first exposure can neutralise the drug and provoke allergy.
- Absolute contraindications: previous intracranial haemorrhage, intracranial neoplasm, active internal bleeding, suspected aortic dissection and recent major trauma, surgery or head injury.
- Relative contraindications: severe uncontrolled hypertension, prolonged or traumatic CPR, pregnancy, active peptic ulcer and oral anticoagulant use.
- Main complication: intracranial haemorrhage, with reperfusion arrhythmias and hypotension also recognised during infusion.
Choosing the agent for a STEMI
A 58-year-old diabetic man presents 90 minutes after the onset of chest pain, with ST elevation in leads II, III and aVF, and primary PCI is not available within the window. The comparison below shows how the common agents differ.
| Feature | Streptokinase | Alteplase | Tenecteplase |
|---|---|---|---|
| Origin | Streptococcal protein | Recombinant tPA | Modified alteplase |
| Fibrin specificity | Low | High | High |
| Antigenicity | High, causes allergy | Low | Low |
| Dosing | Fixed infusion over about an hour | Infusion, with accelerated regimen for STEMI | Single weight-based bolus |
Streptokinase remains common in resource-limited settings because of its low cost, but its allergic and hypotensive effects need monitoring. Fibrin-specific agents act more on the clot and less on circulating fibrinogen, so the main trade-off is still bleeding.
The benefit of fibrinolysis falls with every hour of delay, so door-to-needle time is tracked closely. Weight, blood pressure and bleeding history are checked before any bolus or infusion is started, and the decision is documented in the notes.
Where the exam tries to catch you
Thrombolysis questions turn on the contraindication list and the difference between agents, so the traps below repeat those pairings.
- Trap: streptokinase is repeated in a patient who received it for an earlier myocardial infarction. Correct: antibodies from the first exposure make re-use unreliable and allergic, so an alternative agent is chosen.
- Trap: a blood pressure of 185/105 mmHg is treated as an absolute contraindication. Correct: severe uncontrolled hypertension is relative, so it is lowered before fibrinolysis is given.
- Trap: a stroke five years ago is considered no barrier to thrombolysis. Correct: a past intracranial haemorrhage, or a stroke of unknown cause, is absolute at any time, whereas an ischaemic stroke within the previous 6 months also argues against it.
Frequently asked questions
Why is streptokinase not given a second time?
Streptokinase is a bacterial protein, so the first exposure provokes antibodies that can neutralise a second dose and cause allergic reactions. Re-exposure is therefore avoided, and a different fibrinolytic agent is chosen when one is needed again.
What is the difference between fibrin-specific and non-fibrin-specific thrombolytics?
Fibrin-specific agents such as alteplase and tenecteplase act mainly on plasminogen bound to fibrin in the clot. Streptokinase, which is non-fibrin specific, also activates circulating plasminogen, which increases systemic lysis and bleeding risk.
What are the absolute contraindications to thrombolysis?
Previous intracranial haemorrhage, known intracranial neoplasm, active internal bleeding, suspected aortic dissection and recent major trauma, surgery or head injury are absolute contraindications. Each one raises the risk of catastrophic bleeding, so none is overridden by the benefit.
Why is tenecteplase convenient in pre-hospital settings?
Tenecteplase is given as a single weight-based bolus, which avoids a prolonged infusion. This makes it practical for use before arrival at hospital and for transfer to centres without an immediate catheterisation laboratory.
What is the most serious complication of thrombolysis?
Major bleeding, and especially intracranial haemorrhage, is the most serious complication of thrombolysis. Hypotension, allergic reactions to streptokinase and reperfusion arrhythmias are also recognised, so the patient is monitored during the infusion.