Pharm 101: Thrombolytic agents
Classes
Two major classes: t-PA (tissue plasminogen activator) and streptokinase
Tissue Plasminogen Activator (tPA)
- Naturally occurring enzyme that directly converts plasminogen to plasmin
- Plasmin is the major fibrinolytic enzyme, digesting fibrin
- tPA preferentially activates plasminogen bound to fibrin by several hundred fold therefore is considered to be clot specific, and initiates local fibrinolysis
- Recombinant human t-PA: alteplase, reteplase has a short half-life (5 minutes), therefore heparin is an essential adjunct
- Tenectaplase is a mutant form of t-PA with a longer half-life and can be given as an IV bolus
Streptokinase
- Not an enzyme itself, but a protein synthesised by streptococci
- Combines with plasminogen to form an enzymatic complex that catalyses conversion of plasminogen to plasmin
- Long half-life means that heparin is not required (may increase bleeding risk)
- Prior streptococcal infection may result in antibodies that cause fever, allergic reactions and therapeutic resistance
- Not indicated in acute ischaemic stroke due to increased bleeding risk
Clinical uses
- STEMI
- Unstable PE
- Acute ischaemic stroke
- Severe DVT
Adverse effects
- Haemorrhage:
- Intracerebral haemorrhage
- GI bleeding
- Previous surgery/wounds
Further reading
- Johnston M. Thrombolysis in Acute Stroke
- Nickson C. Thrombolysis for Submassive Pulmonary Embolus
References
- Katzung BG. Basic & Clinical Pharmacology. 14th ed. United States of America: McGraw-Hill Education; 2018. 611-619 p.
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Adult/Paediatric Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Co-creator of the LITFL ECG Library. Twitter: @rob_buttner