Clotting Factors – List, Names and How Clots Form

Our body has mechanisms that prevents blood loss in case of any damage to the blood vessels. The process through which a leaking blood vessel is plugged and then repaired is known as coagulation or clotting. This mainly involves sealing the site of blood vessel injury by changing the liquid state of blood into a gel form that makes up the blood clot.

The clotting of blood is a very complex process, which is orchestrated by aggregation and activation of different chemicals,  cells and components of blood. Disorders at any step in the clotting mechanism could lead to bleeding (hemorrhagic) disorders or abnormal clot formations (thrombosis). Either of these conditions could be lethal.

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How do clots form

The complex process of stopping bleeding through clot formation is set into motion when the damaged blood vessel constricts, and circulating platelets (tiny cell fragments) in the bloodstream start adhering to the damaged walls of the injured blood vessel. The platelets are attracted to the damaged site by collagen, which is a normal constituent of the walls of blood vessels, and gets exposed when a vessel gets damaged.

Contact with this exposed collagen activates a signaling cascade that makes the platelets stick strongly to the damaged site, forming a platelet plug. Eventually, the platelet plug will get enmeshed in a fibrous protein called fibrin, resulting in a blood clot. The process of fibrin clot formation also requires a cascade of enzyme activations.

These enzymes are known as clotting factors, and are normally present in the blood in inactive forms. When the coagulation process begins, the clotting factors start getting activated in a linear fashion by one another. The clotting factors are labeled by roman numerals. However, their numbering sequence does not reflect the order of their activation.

The cascade of clotting factor activation is traditionally viewed as being divided into two separate pathways: intrinsic pathway and extrinsic pathway. Both these pathways ultimately converge into a final common pathway that leads to the formation of the fibrin clot.

  • Extrinsic pathway: The extrinsic pathway, also known as the tissue factor pathway, begins by the activation of a specific clotting factor (factor VII) by tissue damage. This pathway plays a major role in the formation of blood clots.
  • Intrinsic pathway: The intrinsic pathway, also known as contact activation pathway, is stimulated by activation of a specific clotting factor (factor XII) when it comes in contact with exposed collagen. This pathway plays a minor role in the clot formation process.
  • Final common pathway: Both intrinsic and extrinsic pathways finally converge to activate a protein known as prothrombin. Activated prothrombin, also called thrombin, then activates fibrinogen to form the fibrin blood clot.

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Names of clotting factors

The following are the clotting factors involved in the process of blood clot formation.

  • Factor I: Clotting factor I is also known as fibrinogen. It is synthesized by the liver. Fibrinogen is the last enzyme to be activated in the process of clot formation. It is downstream of both intrinsic and extrinsic pathways. Therefore, it can be activated by both pathways. Activation of fibrinogen by thrombin results in the formation of fibrin. The long strands of fibrin form an interconnected meshwork that constitutes the clot.
  • Factor II: Clotting factor II is also known as prothrombin. Like fibrinogen, prothrombin is also synthesized by the liver. Clotting factor II is a step above the clotting factor I in the cascade. Activation of prothrombin by prothrombin activator results in the formation of thrombin. As described above, thrombin then goes on to change fibrinogen into fibrin. Prothrombin is downstream of both intrinsic and extrinsic pathways. Hence, activation of either pathway could result in activation of prothrombin.
  • Factor III: Clotting factor III is also known as thromboplastin or tissue factor. It is produced by activated platelets in the intrinsic pathway. Clotting factor III is also produced by damaged endothelial cells of the blood vessels. Hence, it is also considered a part of the extrinsic pathway. Injured blood vessels cause activation of factor III. The activated factor III (IIIa) then goes on to activate factor VII.
  • Factor IV: Factor IV in the clotting cascade refers to calcium. The source of calcium is bone and food. Calcium functions in both intrinsic and extrinsic pathways. It is necessary for the activation of multiple clotting factors.
  • Factor V: Factor V is also known as labile factor, proaccerin, and Ac-globulin. It is synthesized by the liver and the platelets. Factor V is a part of both intrinsic and extrinsic pathways. Together with factor X, it activates prothrombin.
  • Factor VII: Factor VII is also known as serum prothrombin conversion accelerator (SPCA), proconvertin, and stable factor. It is synthesized by the liver. Factor VII functions in the extrinsic pathway. It is activated by factor III. After its activation, factor VII goes on to activate factor X.
  • Factor VIII: Factor VIII is also known as anti-hemophilic factor, anti-hemophilic factor A, and anti-hemophilic globlin. It is synthesized by platelets and the endothelial lining of blood vessels. Factor VIII is a part of the intrinsic pathway, and is activated by thrombin. In turn, it activates factor X.
  • Factor IX: Factor IX is also known as the anti-hemophilic factor B, plasma thromboplastin component, and Christmas factor. It is produced by the liver, and is a part of the intrinsic pathway. Factor IX is activated by the combined action of calcium and factor XI. In turn, it activates factor X.
  • Factor X: Factor X is also known as Stuart factor or Stuart Prower factor. It is produced by the liver and is activated by both intrinsic and extrinsic pathways. Factor VII activates it through the extrinsic pathway, whereas a combination of factors IX, VIII, and calcium activates it through the intrinsic pathway. Activated factor X helps to convert prothrombin into thrombin.
  • Factor XI: Factor XI is also known as anti-hemophilic factor C and plasma thromboplastin antecedent. It is synthesized by the liver, and is a part of the intrinsic pathway. Factor XI is activated by a combination of prekallikrein, factor XII, and kininogen. It then activates factor IX.
  • Factor XII: Factor XII is also known as Hageman factor. It is synthesized by the liver, and is a part of the intrinsic pathway. It is activated through contact with exposed collagen in injured blood vessels. It activates factor XI. Factor XII also helps in the degradation of clots by activating plasmin.
  • Factor XIII: Factor XIII is also known as fibrin stabilizing factor. It is synthesized by the liver. Calcium and thrombin activate factor XIII, which then cross links fibrin strands in the blood clot, and stabilizes the clot.
  • Prekallikrein: Prekallikrein is synthesized by the liver, and is a part of the intrinsic pathway. It activates factor XI.
  • Kininogen: Kininogen is synthesized by the liver, and is a part of the intrinsic pathway. It activates factor XI.

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