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When is the fibrinolytic system activated?
When the coagulation cascade is activated.
What is the function of the fibrinolytic system?
To remove a thrombus by dissolving fibrin or fibrinogen.
What are the steps involved in the fibrinolytic system?
- Plasminogen is deposited on the fibrin strands in a thrombus.
- Plasminogen is activated to form plasmin.
- Plasmin digests fibrin.
- The thrombus dissolves.
- Normal blood flow resumes.
What are the three plasminogen activators? What type of biomolecule are they?
- t-PA (tissue plasminogen activator)
- Urokinase-like plasminogen activator
They are serine proteases that are unstable in circulating blood.
Give a brief summary of t-PA?
- t-PA is stimulated by pulsatile blood flow, and is being continuously released.
- It exists as a serine protease, which binds to fibrin and activates t-PA.
- This then activates plasminogen.
- Inhibited by PAI-1 and lipoprotein a.
Give a brief summary of plasminogen/plasmin?
- Plasminogen is secreted by the liver and binds to fibrin.
- Cleavage by t-PA generates plasmin.
- Plasmin digests fibrin.
- This causes thrombus lysis, cell migration and ECM remodelling.
- It is inhibited by a2 antiplasmin.
What activates t-PA release?
- Hypoxia (lack of oxygen)
- Bradykinin (peptide that dilates blood vessels)
Name three fibrinolytic drugs?
- Recombinant t-PA
What is the purpose of fibrinolytic drugs?
Break the blood clot and restore normal circulation.
What is the general mechanism of fibrinolytic drugs?
They are enzymes that convert plasminogen to plasmin.
What are fibrinolytic drugs used to treat?
- Myocardial Infarction
- Pulmonary Embolism
- Life threatening Deep Vein Thrombosis
Give an overview of streptokinase?
- Bacterial protein
- Binds to plasminogen, forms an active complex then cleaves plasminogen to generage plasmin.
- Digests all fibrin (no clot specificity)
- Causes antiboy production so it can't be reused for up to 3 years.
Give an overview of recombinant t-PA?
- Directly cleaves plasminogen to plasmin.
- Clot selectivity.
- Non antigenic- doesn't produce antibodies
What are the side effects of Streptokinas and Recombinant t-PA?
- Bleeding- GI and stroke
- Hypersensitivity reactions
What is another method of restoring normal blood flow, aside from fibrinolytic drugs?
- -less occurrence of MI and Stroke
- -better mortality
- But it requires a specialist centre/equipment.
What drug is used to treat life threatening bleeds resulting from the administration of fibrinolytic drugs?
- Tranexamic acid.
- -Inhibits plasmin activation