Clotting Pathway

Question 1

Coagulation Cascade:
What’s the role of the endothelium here?

How is a platelet plug formed?

How is the intrinsic pathway initiated?

How is the extrinsic pathway initiated?

What do both pathways lead to?

Answer 1

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

➋ • 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

➌ When blood comes into contact with the collagen on an injured vessel wall.

➍ When blood comes into contact with the products of damaged tissue (Tissue Factor)

➎ • 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

Question 2

APTT:
Which pathway does this relate to?

How is it measured?

What’s its normal range?

What affects it?

What condition can lead to it being misleadingly raised?

Answer 2

➊ Intrinsic

➋ Contact activator added to blood to active intrinsic pathway and the clotting time is measured in secs

➌ 30-50s

➍ • 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

➎ Anti-phospholipid syndrome

Question 3

PT/INR:
Which pathway does this relate to?

How is it measured?

What’s its normal range?

What affects it?

Answer 3

➊ Extrinsic

➋ TF added to blood to activate extrinsic pathway and the clotting time is measured in secs

➌ PT 12-13s, INR 0.8-1.2

➍ Only Factor VII is involved in the extrinsic pathway and 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