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How does blood coagulate?

How does blood coagulate?

Blood is an essential fluid that carries out the critical functions of transporting oxygen and nutrients to our cells.

Almost 1/10^th of a human’s body weight is made up of blood (male +/- 5.5 liters; female +/-4.5 liters). Besides transporting oxygen and nutrients to our cells, blood plays a key role in our immune system and temperature homeostasis (1).

A few blood facts

- A single pint of donated blood can save 3 human beings.

- Blood is not always red.

- The human body has 100,000 kilometers of blood vessels running through it.

- Platelets, white blood cells, and red blood cells are suspended in plasma; a yellow liquid component of blood.

- Human blood contains atoms of metals, including a bit of gold.

- Red blood cells lack nuclei.

- There are 4 blood types that vary by population: A, B, AB, and O. Each blood type can be either RhD positive or RhD negative, giving a total of 8 main blood groups.

Blood clotting or coagulation – the blood coagulation cascade

Blood clotting is a multi-step process known as the blood coagulation cascade (2). The blood coagulation cascade is classified into three pathways—the extrinsic pathway, the intrinsic pathway, and the common pathway (Figure 1).

Figure 1. Blood coagulation cascade. Download the pathway poster here.

The extrinsic pathway is released by damaged cells and tissues. It is also known as the tissue factor pathway. The intrinsic pathway is a parallel pathway for thrombin activation by factor XII (Figure 2). It is triggered by blood encountering collagen fibers in the broken wall of a blood vessel. Both pathways eventually produce a prothrombin activator, triggering the common pathway in which prothrombin becomes thrombin followed by the conversion of fibrinogen to fibrin (3). It is important to note that this is a simplified description and research suggests that this process is much more complex. However, it is a useful approach for better understanding blood clotting.

Figure 2. Immunofluorescent analysis of (-20℃ Ethanol) fixed HepG2 cells using Factor XII antibody (66089-1-Ig) at a dilution of 1:100 and Alexa Fluor 488-conjugated AffiniPure Goat Anti-Mouse IgG(H+L).

13 blood coagulation factors

Our body activates coagulation factors that solidify blood into a clump by forming a special protein and fixing the clump at the wound. Humans have 13 clotting factors (4), the majority of which are produced in the liver (Table 1).

Coagulation Factor	Common Name	Source	Pathway	Classification
Factor I	fibrinogen	liver	common	fibrinogen family
Factor II (Figure 3)	prothrombin	liver	common	vitamin K dependent proteins
Factor III	tissue factor or thromboplastin	damaged tissue cells, platelets release thromboplastin	extrinsic	N/A
Factor IV	calcium ions	bone, and absorption through the lining of the small intestine	extrinsic, intrinsic, and common	N/A
Factor V (Figure 4)	proaccelerin or labile factor	liver and platelets	N/A	fibrinogen family
Factor VI	accelerin, no longer used	N/A	common	N/A
Factor VII	proconvertin or stable factor	liver	extrinsic	vitamin K dependent proteins
Factor VIII (Figure 5)	anti-hemophilic factor	platelets and the lining of blood vessels	intrinsic	fibrinogen family
Factor IX	plasma thromboplastin component / Christmas factor	liver	intrinsic	vitamin K dependent proteins
Factor X	Stuart Prower factor	liver	common	vitamin K dependent proteins
Factor XI	plasma thromboplastin antecedent	liver	intrinsic	contact family
Factor XII (Figure 6)	Hageman factor	Liver	intrinsic	contact family
Factor XIII	fibrin stabilizing factor	liver	common	fibrinogen family

Table 1. Clotting factors in the blood (N/A - not applicable).

Figure 3. Immunohistochemistry of paraffin-embedded human liver tissue slide using F2 antibody (66509-1-Ig) at a dilution of 1:150 (under 10x lens).

Figure 4. Immunohistochemistry of paraffin-embedded human liver cancer tissue slide using F5 Antibody (20963-1-AP) at a dilution of 1:200 (under 40x lens). Heat mediated antigen retrieved with Tris-EDTA buffer(pH9).

Figure 5. Immunofluorescent analysis of (-20℃ Ethanol) fixed HUVEC cells using F8 antibody (21485-1-AP) at a dilution of 1:25 and Alexa Fluor 488-conjugated AffiniPure Goat Anti-Rabbit IgG(H+L).

Figure 6. Immunohistochemistry of paraffin-embedded human liver cancer tissue slide using Factor XIIIA antibody (66325-1-Ig) at a dilution of 1:400 (under 40x lens). Heat mediated antigen retrieved with Tris-EDTA buffer(pH9).

What if the blood does not clot well? Clotting disorders

Bleeding disorders occur when blood does not clot fast enough. Relatively common deficiencies of factors II, V, VII, X, and XII are related to blood clotting problems or abnormal bleeding problems. Hemophilia A and B are widely known clotting disorders. Blood does not clot correctly, which results in excess bruising and bleeding internally. The most common type is hemophilia A, which reflects a low level of clotting factor VIII, while hemophilia B displays a low level of factor IX (5, 6).

Closing remarks

A healthy body protects itself by clotting blood when injured, removing clots when they are no longer needed, and preventing clots from overgrowing. The entire blood clotting process is undoubtedly complicated; however, learning more about it will help in the discovery of new ways to improve coagulation as well as identifying how to prevent it from occurring inappropriately.