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# Thrombolytics (fibrinolytics)

Drugs that dissolve a clot that is already blocking a vessel, by turning plasminogen into plasmin. Bleeding is their main risk.

Updated 2026-11-01

## What they are

Plasminogen activators given intravenously in acute ST-elevation myocardial infarction, acute ischaemic stroke and massive pulmonary embolism. Recombinant tissue plasminogen activator (alteplase) and its engineered variants (tenecteplase, reteplase) prefer fibrin-bound plasminogen; streptokinase, a bacterial protein, does not.

## Mechanism of action

They convert plasminogen into plasmin, a protease that digests the fibrin mesh of the thrombus. At therapeutic levels plasmin also degrades fibrinogen and factors V and VIII and dissolves the fibrin of normal haemostatic plugs, which is why haemorrhage, above all intracranial, is the main toxicity.

Target: Plasminogen → plasmin

## Key points

- Time is tissue: benefit is greatest when given early after symptom onset
- Absolute contraindications: prior intracranial bleed, known brain lesion, recent ischaemic stroke or head trauma, aortic dissection, active bleeding
- Rule out haemorrhage with brain imaging before giving it in stroke
- Tenecteplase and reteplase last longer than alteplase, so they are given as boluses
- Streptokinase is antigenic: allergy, fever and resistance in people with anti-streptococcal antibodies

## Drugs in this class

- [**Alteplase** Recombinant tissue plasminogen activator that dissolves the clot in acute ischaemic stroke, heart attack and massive… Plasminogen (the zymogen of plasmin), bound to fibrin](https://durgical.com/en/pharmacology/alteplase/)
- [**Tenecteplase** An engineered tissue plasminogen activator that lasts longer than alteplase, so it is given as a single bolus in heart… Plasminogen (the zymogen of plasmin), bound to fibrin](https://durgical.com/en/pharmacology/tenecteplase/)
- [**Reteplase** A shortened recombinant tissue plasminogen activator with a longer half-life, given as two boluses in acute myocardial… Plasminogen (the zymogen of plasmin), bound to fibrin](https://durgical.com/en/pharmacology/reteplase/)
- [**Streptokinase** A streptococcal protein that forms a complex with plasminogen to dissolve clots. Cheap but antigenic and not… Plasminogen (streptokinase–plasminogen activator complex)](https://durgical.com/en/pharmacology/streptokinase/)

## Others in the class

- urokinase

## Test yourself

Think of the answer, then tap the question to see it.

## Which enzyme do all thrombolytics end up generating?

Plasmin, from plasminogen.

## What is the most feared adverse effect of thrombolysis?

Intracranial haemorrhage.

## Why does alteplase cause less systemic plasmin than streptokinase?

It activates plasminogen mainly when both are bound to fibrin in the clot.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 36 (McGraw Hill, 2023); Farmacología básica y clínica (Katzung), 16.ª ed., cap. 34 (McGraw Hill, 2025); [Alteplase Injection: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a625001.html) (MedlinePlus (U.S. National Library of Medicine), 2025); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/) (World Health Organization, 2025).

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