What is haemostasis?
Haemostasis (also spelled as hemostasis, depending on dialect) is related to inflammation: it only tends to happen during vascular injury. In the brain, this process can happen when the blood vessels are injured, such as in slit haemorrhages or in trauma. It is split into primary and secondary haemostasis. Under normal circumstances, this function serves to help stitch up wounds, but presence of inhibitors or factor deficiencies can lead to abnormal bleeding times. As the Smart Art Graphic below shows, there needs to be a balance between the processes of clotting (coagulation) and bleeding (fibrinolysis) in order for the body to work properly.
Primary haemostasis takes place over several stages and ultimately results in the formation of a platelet plug over the site of the wound. They are explained below.
- The blood vessels is normal with intact wall and is covered with a single layer of endothelial cells
- When the endothelial wall is damaged, the basement membrane and collagen fibres are exposed to the bloodstream.
- Platelets move in and start to stick to the collagen fibres.
- The adhered platelets release granules and attract more platelets to the site.
- A plug of aggregated platelets is formed.
Secondary haemostasis is also known as the coagulation cascade, and it ultimately results in the formation of a fibrin clot, which is relatively stable compared to the platelet plug. The coagulation cascade has two components: the extrinsic pathway and the intrinsic pathway. They merge together to form the common pathway.
How are the pathways activated?
The intrinsic pathway is activated by the exposure of negatively charged surfaces, whilst the extrinsic pathway is activated by tissue factor. Each of the ingredients of the pathway have Roman numbers based on their order of discovery: I’ve added the English equivalents below.
What are each of the pathway made of?
Each of the components within the three pathways is listed in the table below.
- Factors II, VII, IX, X, XI, XII, XIII (2, 7, 9, 10, 11 and 13) are all known as zymogens: they are all inactive at first, but they are activated by enzymes.
- Factors II, VII, IX and X (2,7, 9 and 10)are known as vitamin K dependent groups: they are produced in the liver and are dependent on vitamin K to become activated.
- Factors XII and XI (12 and 11) are members of the contact group: they are activated by exposure of collagen fibres
- Factors I, II, V, VIII and XIII (1,2,5,8 and 13) are all thrombin sensitive.
What are the functions of tissue factor?
Tissue factor plays several roles in the process of haemostasis (in the intrinsic pathway):
- Forms a stable complex with Factor VII (7).
- Converts FVII (7) to Factor VIIa (activated factor 7)
- Increases the affinity of FVII (7) for Factor X (10)
- Enhancing the ability of FVII to activate FX, the first component of the common pathway.
How does the coagulation cascade run?
The coagulation cascade is demonstrated in the Smart Art Graphic below. Each activated factor activates the next factor in line. The intrinsic and extrinsic pathways are activated first. The extrinsic pathway intersects with the FIXa complex (which activates FX). The Factor Xa complex activates prothrombin to form thrombin.