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.