Blood Coagulation/ thrombolysis/ anticoagulant drugs/ anti-platelet agents Flashcards
Role of Vitamin K in synthesis of coagulation factors.
Negatively charged residues on coagulation proteins often depend on this. all synthesised in liver, F II, VII, IX, and X are post-translationally modified to add an extra carboxy group on GLA, which carries a strong negative charge, which is a vitamin k dependent reaction.
Explain the mechanism of action of Warfarin.
Inhibits coagulation cascade by preventing the correct synthesis of FII, VII, IX, and X as well as proteins C and S (vitamin K epoxide reductase inhibitor)
What is the role of endogenous heparin in the regulation of coagulation.
Intact epithelium expresses heparin proteoglycans which bind and activate antithrombinIII, secretes PGI2 and NO which actively inhibit platelet aggregation, releases plasminogen activator to degrade any local/adjacent fibrin rich clots
Explain the moa of heparin.
Binds to antithrombin III inducing a conformational change that makes ATIII a more efficient inactivator of coagulation factors
What are the different forms of therapeutic heparin
Unfractionated heparin, LMWH, fondaparinux, all effectively inactivate factor Xa.
IV anticoagulants.
Heparin and LMWH: cheap, immediate, short term use.
Oral anticoagulants.
Warfarin: slow onset/offset, long term use, cheap.
Dabigatran.
Direct thrombin inhibition
Compare and contrast different types of blood clotting tests.
PT test/INR: assesses tissue factor pathway (extrinsic)
aPTT: assesses intrinsic pathway
TT: thrombin time to assess clotting rate in final common pathway
fibrinogen quantification and d-dimer tests
MOA of unfractionated heparin.
Inhibits IIa by binding to ATIII
MOA of LMWH.
Binds to antithrombin III-> LMWH-antithrombin III complex inhibits:
-factor Xa
-less of an effect on thrombin (2a).
