COAGULATION CASCADE

The coagulation cascade is a series of reactions, catalysed by protein enzymes known as coagulation 'factors'. When activated, these factors trigger the conversion of other factors in the coagulation cascade resulting in secondary haemostasis.

Secondary haemostasis refers to the stabilisation of activated platelets due to the actions of strands of fibrin. These generate a 'stable mesh' the main component in a thrombus (clot).

The activation and adherence of platelets to the damaged endothelium (primary haemostasis), and vascular response to injury (e.g. vasoconstriction) are the other key components involved in thrombus formation and haemostasis.

Fibrin is converted from its precursor fibrinogen by thrombin and is the end-product of the chain of reactions that make up the coagulation cascade.

The coagulation cascade can be divided into three segments or pathways: the intrinsic, extrinsic and common pathways. Coagulation is more complex than its depiction in the coagulation cascade, but the cascade is a useful starting point to understanding laboratory tests of coagulation.
Without regulatory mechanisms, the positive feedback loop triggered by thrombin in the intrinsic pathway would continue indefinitely and cause dangerous levels of clotting in the blood.

For this reason, various proteins inhibit aspects of the coagulation cascade once enough thrombin has been produced.

Protein C is produced in response to thrombin binding to the receptor thrombomodulin on the vascular endothelium. This leads to protein S activation which then breaks down factors Va and VIIIa in a negative feedback loop.

Antithrombin is a natural anticoagulant that is produced by the liver and destroys factors XIa, Xa and thrombin.

Heparin and fondaparinux enhance the natural effects of antithrombin in inhibiting thrombin and factor Xa.

Tissue factor pathway inhibitor is a protein that binds to and inactivates factor VIIa and factor Xa.