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 or thrombolytics are drugs that lyse thrombi that have already been formed. They’re used clinically to reopen arteries that have been occluded, most commonly in connection with AMI. PCI is preferred instead of fibrinolytics for this purpose, but they can also be used for pulmonary embolisms, ischaemic stroke and to reopen occluded shunts or cannulas.
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, which gives it 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.
These drugs inhibit the pathologically increased fibrinolysis. They’re indicated to stop severe bleeding like during menorrhagia, tooth extraction or during surgery.
Tranexamic acid is given IV or orally and inhibits the conversion of plasminogen into plasmin.
Aprotinin inhibits other proteolytic enzymes that convert plasminogen into plasmin. It’s also used as an antidote to fibrinolytic 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.
10. Anticoagulants, antiplatelet drugs
12. Drugs affecting hematopoiesis