Pharm 101: Thrombolytic agents


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
  • 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
  • Unstable PE
  • Acute ischaemic stroke
  • Severe DVT
Adverse effects
  • Haemorrhage:
    • Intracerebral haemorrhage
    • GI bleeding
    • Previous surgery/wounds
Further reading
  • Katzung BG. Basic & Clinical Pharmacology. 14th ed. United States of America: McGraw-Hill Education; 2018. 611-619 p.
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MBBS CCPU (RCE, Biliary, DVT, E-FAST, AAA) Rob is an Emergency Medicine Advanced Trainee based in Melbourne, Australia. He has special interests in medical education, ECG interpretation, and the use of diagnostic and procedural ultrasound in the undifferentiated and unwell patient.

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