Why The Intrinsic Pathway Needed When The Extrinsic Pathway of Blood Clotting Exists

In this article we will try to find out why the intrinsic pathway needed when the extrinsic pathway of blood clotting exists? To find the answer to this question, it is essential to understand the process of blood clotting and the approaches our body employs to accomplish it. Hence, with a brief explanation of the process of blood clotting (also called hemostasis or blood coagulation), we will explore the reason behind the different pathways of blood clotting.

Blood clotting

The process of blood clotting is extremely important for us. We can understand the significance of blood clotting by recognising the fact that failure of blood clotting can lead to death. Every year, over 0.1 million people die due to the various disorders of blood clotting. This is because blood is a vital body fluid, and our body cannot tolerate its loss. That’s why we have this essential mechanism, which is blood clotting.

The process of preventing blood loss is called blood clotting or coagulation of blood. It is a multi-step process and completes in a series of reactions catalyzed by many enzymes, hence it is also called coagulation cascade.

Mechanism of Blood clotting (Hemostasis)

The initiation of coagulation begins when there is an injury, also called trauma, in blood vessels. Blood clotting includes four major steps –

Injury

Rupturing of blood vessels occur. Blood escape from body.

Vascular spasm

Smooth muscles in blood vessels contract due to the release of serotonin by platelets

Platelet Plug Formation

Some platelets at the site of injury become sticky and start adhering to each other which form platelet plug

Coagulation

Multi-steps complex cascade of reactions that result into the formation of clot

Why The Intrinsic Pathway Needed When The Extrinsic Pathway of Blood Clotting Exists

There are two pathways for the initiation of coagulation depending on the type of injury

1. The extrinsic pathway

2. The intrinsic pathway

When does the extrinsic pathway begin?

This pathway activates when there is an external trauma, meaning the damage occurs not only in blood vessels but also occurs in surrounding tissues (tissues outside the blood vessels). Escape of blood from the blood vessels occurs in such damage. This pathway is called external because the tissue factor- the tissue thromboplastin, a substance which is” extrinsic to blood” responsible for activation of it comes from the external source (from surrounding damaged tissue) and not from blood.

The tissue thromboplastin, also called factor-III activates factor VII (inactive) to active factor VIIa. Now the extrinsic pathway enters into the common pathway when factor VIIa acts on factor X and converts them to active factor Xa.

When does the intrinsic pathway begin?

This pathway activates when the damage is internal to blood vessels (i.e. tearing of the endothelial layer). Blood may not escape from the blood vessels. The negatively charged collagen fibres, situated below the endothelial layer, get exposed to blood due to the tearing of endothelium.

As soon as the blood comes in contact with the collagens a cascade of proteins activates and their interactions result in the beginning of intrinsic pathway. The pathway begins with the activation of Prekellikrein to active kellikrein which together with kininogen activates factor XII (Hageman Factor), XI, IX, and X.  All these reactions occur sequentially in the coagulation cascade.

Since injuries are different, hence the pathways for coagulation are also different. Some injuries lead to bleeding from the organs (or tissue). The extrinsic pathway is followed in such cases. On the other hand, some injuries occur only inside the blood vessels, damaging of endothelial layer only. The intrinsic pathway followed in such cases, which is a slower process. This is why the intrinsic pathway needed when the extrinsic pathway of blood clotting exists.

Extrinsic Pathway Vs Intrinsic Pathway

The Common Pathway

Both Extrinsic and intrinsic pathways ultimately converge to a common pathway in which activated factor Xa converts Prothrombin into Thrombin. Thrombin converts soluble Fibrinogen into insoluble Fibrin which leads to the clot formation.

Why does blood clots when it is placed in a test tube or when it is taken out of the body.

The intrinsic pathway is also activated when blood comes in contact with negatively charged foreign surfaces such as glass, synthetic plastics, fabrics and more (medical devices). This activation is also called contact activation. These negatively charged foreign surfaces activate factor XII; therefore, the cascade of intrinsic pathways proceed as mentioned above, through activation by collagen fibres in sub-endothelial layer of blood vessels. This explains why blood clots in test tubes, in any containers with negatively charged surfaces, or simply, when blood is taken out of the body.

List of 13 clotting factors

While there are known clotting factors labelled, as Factor I through Factor XIII, the total numbers of factors is not 13; there are actually only 12. Factor VI once believe to be a distinct factor, was later recognised as the activated form of factor V known as ‘Va’. Below is a list of all the blood clotting factors-

Numbers	Factors	Fuctions
Factor I	Fibrinogen	Forms fibrin thread
Factor II	Prothrombin	Its active form (IIa) activates platelets factors I, V, VII, VIII, XI, XIII
Factor III	Tissue Thromboplastin (also called tissue factor)	Cofactor of factor VIIa
Factor IV	Calcium (Ca++)	Required for coagulation factors to bind to phospholipids, which were formerly known as factor IV
Factor V	Labile factor (also called proaccelerin)	Cofactor of factor X with which it forms the prothrombinase complex
Factor VI	Unassigned	N/A
Factor VII	Stable factor(also called proconvertin)	Activates factor IX, X; increases the rate of catalytic conversion of prothrombin into thrombin
Factor VIII	Antihaemophilic factor	Cofactor of factor IX with which it forms the tenase comlex
Factor IX	Plasma thromboplastin	Activate factor X, forms tenase complex with factor VIII
Factor X	Stuart Prower Factor	Activate factor II, forms prothrombinase complex with factor V
Factor XI	Plasma Thromboplastin Antecedent (PTA)	Activate factor IX
Factor XII	Hageman factor (also called glass factor)	Activate factor XI and VII, prekellikrein and plasminogen
Factor XIII	Fibrin-Stabilizing factor	Crosslinks fibrin threads

References:

1. https://www.ncbi.nlm.nih.gov/books/NBK507850/#:~:text=The%20intrinsic%20pathway%20responds%20to,continue%20coagulation%2C%20the%20common%20pathway.
2. https://www.britannica.com/science/bleeding/Intrinsic-pathway-of-blood-coagulation
3. https://pediaa.com/difference-between-intrinsic-and-extrinsic-pathways-in-blood-clotting/
4. https://teachmephysiology.com/immune-system/haematology/coagulation/
5. https://www.sciencedirect.com/topics/computer-science/intrinsic-pathway
6. https://en.wikipedia.org/wiki/Coagulation
7. https://labpedia.net/coagulation-part-1-blood-coagulation-process-coagulation-factors-and-factors-deficiency/