top of page

Clotting Pathway

Coagulation Cascade

Endothelial cells naturally release anti-thrombic chemicals to prevent platelet adhesion and thrombus formation. Therefore, damage to them leads to clot formation.


A platelet plug is formed by:

  • Damage to blood vessel exposes the collagen on its surface, which vWF then binds to

  • Platelets adhere to the damaged endothelium via vWF, leading to their degranulation → vasoconstriction, attraction of more platelets

  • Fibrin mesh is formed to stabilise the platelet plug


It includes 2 different pathways:

  • The Intrinsic pathway is initiated when blood comes into contact with the collagen on an injured vessel wall.

  • The Extrinsic pathway is initiated when blood comes into contact with the products of damaged tissue (Tissue Factor/TF).


Both pathways lead to the:

  • Formation of factor Xa, which combines to with factor Va on the surface of activated platelets (in the presence of Ca ions) to form the prothrombinase complex

  • The prothrombinase complex cleaves prothrombin → thrombin

  • Thrombin then cleaves fibrinogen → fibrin so that a mesh is formed

ree

APTT

This relates to the Intrinsic pathway. It's measured by adding contact activator to blood to active the intrinsic pathway, and the clotting time is measured in seconds. NR is 30-50s.


Causes of a raised APTT:

  • Anything that affects Factor VIII (Haemophilia A/VWD), Factor IX (Haemophilia B), or Factor XI (Haemophilia C)

  • Same as extrinsic pathway - Warfarin/Vit K deficiency, Liver disease, DIC


The result can be misleadingly raised by Anti-phospholipid syndrome.


PT/INR

This relates to the Extrinsic pathway. It's measured adding TF to blood to activate extrinsic pathway, and the clotting time is measured in seconds. NR for PT is 12-13s, and 0.8-1.2 for INR.


Causes of a raised PT/INR - Only Factor VII is involved in the extrinsic pathway, but deficiencies of it are very rare. Therefore, it’s only really affected by reduced synthesis or increased consumption of TF. This can be due to:

  • ↓synthesis - Warfarin/Vit K deficiency, Liver disease

  • ↑consumption - DIC



bottom of page