Introduction
A series of events known as the coagulation cascade, or secondary hemostasis, entails the simultaneous activation of clotting factors to achieve hemostasis. Hemostasis refers to the cessation of bleeding. The hemostasis process starts as soon as an injury occurs. Typically, there are two categories: primary and secondary. The development of an unstable blood clot at the site of damage is a necessary component of primary hemostasis. Secondary hemostasis guarantees the blood clot's stability and the injured tissue's healing. These clotting factors must cooperate throughout the entire process to stop the bleeding and, in the end, create a blood clot that aids in wound healing. This article aims to discuss the different clotting factors involved in the coagulation cascade alongside the various pathways through which hemostasis can be achieved.
What Are the Clotting Factors?
Clotting factors refer to the serine proteases that are present in the blood in an inactivated form known as zymogens. These factors are activated once they are placed with their respective glycoprotein co-factor and thus assist in the blood clotting process. To summarize, the important functions of clotting factors include:
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Control the bleeding from tissues upon injury.
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Preventing undesirable loss of blood.
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Converting blood into a thick gel-like consistency to stop the bleeding at the injury site.
These coagulation factors are manufactured by the liver and are introduced into the coagulation cascade, employing two distinct pathways. These pathways will be discussed in detail in the next section of the article. A total of 12 coagulation factors are discovered, namely:
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Factor I: Fibrinogen
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Factor II: Prothrombin
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Factor III: Thromboplastin
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Factor IV: Ionized Calcium (Ca++)
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Factor V: Proaccelerin
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Factor VI: (No longer a blood coagulation factor)
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Factor VII: Stable factor or Proconvertin
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Factor VIII: Antihemophilic factor
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Factor IX: Christmas factor
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Factor X: Stuart-Prower factor
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Factor XI: Plasma Thromboplastin antecedent
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Factor XII: Hageman factor
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Factor XIII: Fibrin-stabilizing factor
All of these factors are activated, as required, by a chain of reactions. Their activated forms are written by adding the suffix ‘a’ after the factor numeral. For example, Factor I, when activated, is mentioned as factor Ia.
What Are the Coagulation Pathways?
The process of coagulation is carried out in three different pathways. These are:
Extrinsic Pathway
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Two major factors involved: factor III and factor VII
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Involves initiation by factor III (tissue factor)
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Factor VII (proconvertin) is activated with the help of Vitamin K.
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Upon injury to the skin tissue, factor III is exposed. It binds to the calcium and activates factor VIIa to activate factor X further.
Intrinsic Pathway
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Major factors involved: XII, XI, IX, and VIII
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Initiated by exposure of factor XII (Hageman factor) to collagen, thus converted to activated XIIa.
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Factor XIIa is responsible for activating factor XI (plasma thromboplastin antecedent) to XIa.
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Factor XIa activates factor IX (Christmas factor) with the help of calcium ions.
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Factor VIII (Antihemophilic factor) is present in blood and activated by thrombin (factor IIa).
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Now, factor IXa, VIIIa, and Ca++ form a complex that allows for the activation of factor X.
Common Pathway
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Major factors involved: X, V, II, I, and XIII
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Initiated by the formation of a prothrombinase complex by binding of factors Xa, Va, and Ca++.
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This complex activates factor II (prothrombin) into IIa (thrombin).
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Factor IIa (thrombin) converts factor I (fibrinogen) into Ia (fibrin).
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Thrombin also activates factor XIII (stabilizing factor) to XIIIa.
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Factor XIIIa binds with Ca++ to establish stronger crosslinks between fibrin fibers, thus stabilizing the clot.
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Hemostasis is achieved.
These pathways collaborate to achieve hemostasis by forming a stable blood clot at the injury site. Both the extrinsic and intrinsic pathways enter the common pathway by activating factor X (Stuart-power factor). The common pathway is inevitable, irrespective of the initial pathway. The thrombin (factor IIa) is a major player in the common pathway that has a significant role in achieving hemostasis.
What Are Coagulation Disorders?
Coagulation disorders are present in people who are deficient in at least one of the clotting factors mentioned above. These disorders either make it difficult to form a stable blood clot or cause excessive clotting. Both of these phenomena are hazardous to one's life. Some of the most common coagulation disorders include:
Von Willebrand Disease
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Most common bleeding disorder
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Characterized by deficiency in von Willebrand factor
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Usually impacts primary hemostasis due to inadequate platelet aggregation
Hemophilia A, B, and C
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Hereditary disorder occurs due to genetic mutations in clotting factor genes.
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Type A is characterized by a deficiency of factor VIII
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Type B is due to a deficiency of factor IX.
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Type C is a result of a deficiency of factor XI.
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All types of hemophilia have a major impact on the intrinsic pathway of the coagulation cascade.
Vitamin K Deficiency
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Mainly occurs due to dietary deficiency, or the inability of the body to absorb adequate amounts of vitamin K.
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Vitamin K plays a key role in activating factors II, VII, IX, and X.
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Deficiency of vitamin K affects all three pathways of the coagulation cascade.
Conclusion
The coagulation cascade involves sequential activation of proteins called clotting factors. It is a pivotal process that aims to achieve hemostasis and prevent excessive blood loss during an injury. Hemostasis is carried out through 3 distinct pathways: extrinsic, intrinsic, and common. Both intrinsic and extrinsic pathways lead to the activation of factor X, which enters the common pathway to bring about the result of forming a stabilized blood clot at the site of injury. Certain genetic disorders tend to result in a deficiency of one or more clotting factors, thus giving birth to coagulation disorders.
