11. Fibrinolytics, antifibrinolytics, hemostatic agents

Last updated on November 28, 2019 at 14:33

Fibrinolysis

The fibrinolytic system is activated simultaneously with the coagulation cascade. The function of this system is to dissolve the clot after the bleeding has stopped and the damage has been repaired.

Many proteins are involved, most important tissue plasminogen activator (TPA), plasminogen and plasmin. TPA, factors XIa and XIIa and kallikrein all activate plasminogen into plasmin. Plasmin is a proteolytic enzyme similar to trypsin which then breaks down fibrin and coagulation factors, ultimately lysing the clot. After lysing the clot is plasmin quickly inactivated by plasmin inhibitors to prevent plasmin from lysing other clots that are not ready to be lysed yet in other parts of the body.

Fibrinolytics

Compounds:

  • Natural
    • Streptokinase
    • Urokinase
  • Recombinant tPA analogues
    • Alteplase
    • Duteplase
    • Tenecteplase

Indications:

  • Early STEMI
  • Early ischaemic stroke
  • Massive pulmonary embolism

Fibrinolytics or thrombolytics are drugs that lyse thrombi that have already been formed. PCI is preferred instead of fibrinolytics, if available.

Mechanism of action:

The historical drug is streptokinase, which is actually a virulence factor of streptococcus bacteria. It activates plasminogen. Because it is a viral antigen does it induce an immune reaction with a fever. It’s therefore not used for systemic use but only for local use with the help of a catheter. Because streptokinase activates plasminogen even if the plasminogen isn’t bound to fibrin, it has an increased risk of bleeding.

Alteplase, duteplase, tenecteplase and reteplase are recombinant TPA-like molecules. These molecules act mostly on plasminogen that is bound to fibrin, so they have lower risk of bleeding than streptokinase.

Antifibrinolytics

Compounds:

  • Tranexamic acid
  • Aminocaproic acid
  • Aprotinin

Indications:

  • Stop severe haemorrhage
  • Antidote to fibrinolytic drugs.

Mechanism of action:

Tranexamic acid inhibits the conversion of plasminogen into plasmin.

Aprotinin inhibits other proteolytic enzymes that convert plasminogen into plasmin.

Haemostatic drugs

These drugs stop bleeding by mechanisms other than inhibiting fibrinolysis. They can especially be used when patients who take anticoagulants or antiplatelets start bleeding externally, in which case the bleeding would take a long time to stop by itself.

Spongostan is a type of sponge made of gelatine which induces haemostasis when applied directly to a bleeding. It’s also available as a powder.

Thrombin powder also induces haemostasis when applied directly to a bleeding.

Styptics are haemostatic agents that work by contracting tissue to seal damaged blood vessels. These agents contain astringents, which are compounds that cause vessels to contract. Adrenaline is sometimes used as an astringent.

For systemic use can plasma preparations, thrombocyte concentrates, coagulation factors and vitamin K be administered to prevent bleeding.

Ethamsylate is a drug that increases thrombocyte aggregation. It’s used to prevent parenchymal bleeding after surgery.


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10. Anticoagulants, antiplatelet drugs

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12. Drugs affecting hematopoiesis

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