coagulation cascade

what is coagulation?

formation of a blood clot

what are the 2 coagulation pathways?

intrinsic and extrinsic

what is the extrinsic pathway triggered by?

external trauma causing blood to escape circulation

what is the intrinsic pathway triggered by?

internal damage to the vessel wall

draw the coagulation cascade

outline the basics of the extrinsic pathway

- factor VII and factor III form a complex called the TF-VIIa complex
- TF-VIIa activates factor X into Xa

outline the basics of the intrinsic pathway

- factor XII activated
- factor XI activated
- factor IX activated
- factor IXa combines with factor VIII to form enzyme complex that activates factor X

what happens to the Xa?

combines with factor Va and stimulates prothrombin to thrombin activation

what does thrombin do?

- stimulates fibrinogen to fibrin activation
- activates XIII to XIIIa

what does XIIIa do?

stimulates fibrin to form cross-link fibrin clots

what regulates the clotting cascade?

- protein C
- protein S
- antithrombin

how is protein C activated?

contact with thrombomodulin which is activated by thrombin

what does protein C do?

degrades factors Va and VIIIa

what does protein S do?

also degrades factor Va and VIIIa

is antithrombin ever inactive?

no, but it can be activated further by heparins

what does antithrombin do?

degrades:
- thrombin (IIa)
- IXa
- Xa
- XIa
- XIIa

how is the blood clot broken down?

fibrinolysis

how does fibrinolysis occur?

- endothelial cells secrete tissue plasminogen activators (tPAs)
- tPAs convert plasminogen into plasmin
- plasmin cleaves the fibrin within the thrombus

which clotting factors require vitamin K for their formation?

II, VII, IX, X (2,7,9,10)
1972

what are 3 examples of anticoagulants?

- warfarin
- heparin
- aspirin

how does warfarin act as an anticoagulant? (3)

- vitamin K antagonist
- competes with vitamin K
- inhibits vitamin K so vit K-dependent factors cannot be synthesised

should warfarin be used in pregnancy?

no

why should warfarin not be used in pregnancy?

teratogenic medication that can cross the placenta

what does teratogenic mean?

can cause developmental and birth defects

how does heparin act as an anticoagulant?

activates antithrombin III

what does antithrombin III do?

- inhibits thrombin by binding to active site
- hence thrombin cannot activate fibrinogen to fibrin and XIII to XIIIa

how does aspirin act as an anticoagulant? (2)

- its is better defined as an anti-platelet
- it inhibits platelet synthesis

what are hirudins?

drugs that are direct thrombin inhibitors

what are some examples of hirudins?

- lepirudin
- bivalirudin