Coagulation

Question 1

What is coagulation?

Answer 1

It is the formation of a fibrin clot or thrombus. This fibrin clot is strong, insoluble and it’ll trap red blood cells and white blood cells and it serves to reinforce the platelet plug. So when platelet plug forms this aggregation of platelets, it is quite weak and this fibrin clot formation will then reinforce this platelet plug and make it much stronger and this will lead to the entrapment of blood cells. The colour of the thrombi will depend on the type of cells caught, so you get a white thrombus or red thrombus.

Question 2

What is the coagulation cascade?

Answer 2

The formation of the fibrin clot is regulated by a cascade called the coagulation cascade. It is a complex enzyme cascade. It ultimately leads to the conversion of soluble fibrinogen to insoluble fibrin.

• There are proteolysis enzymes involved and each enzyme will cleave and activate the next one in the cascade.

There are 2 pathways:

1. Intrinsic pathway/contact pathway
   - Where you expose blood for example to an abnormal surface such as glass, you will lead to clotting by the activation of this pathway.
   - All the components are present in the blood and that’s what initiates the clotting cascade and clot formation
2. Extrinsic/In vivo pathway
   - Activated in the presence of tissue damage.
   - Some components are coming from outside the blood
   - If you have tissue damage, this leads to the release of tissue factor for example, which will lead to the activation of coagulation cascade.

Both these pathways converge at factor 10, and factor 10 will be cleaved to 10a which is initiated by either factor 9a or factor 7a depending on the pathway activated.

In the context of atherosclerosis and thrombi formation, it’s the extrinsic pathway that is activated:

Factor 10 -> Factor 10a -> Thrombin -> Soluble fibrogen -> Insoluble fibrin -> Fibrin polymers -> highly insoluble plug -> start to trap blood cells -> FORMS CLOT

Question 3

What is the role of thrombin?

Answer 3

• Thrombin cleaves fibrinogen, which produces lots of fragments of fibrin. These are highly insoluble and polymerised quickly to form an insoluble fibrin meshwork.
• Thrombin can be activated by Factor 13 and this strengthens fibrin links further.
• It can stimulate platelet aggregation
• Can stimulate proliferation
• It can regulate smooth muscle contraction

Question 4

What is the role of the liver in coagulation?

Answer 4

1. The liver synthesises clotting factors
2. Vitamin K
   - Known as the ‘Koagulation’ vitamin
   - Lipid soluble
   - Essential for the synthesis of Factors II, VII, IX, X
   - Most vitamin K from our dietary sources
   - Synthesised in the GIT
3. Bile salts are essential for vitamin K reabsorption and vitamin K is essential for clotting factors