What is Blood Coagulation?
Process of blood clotting is called as blood coagulation. The blood coagulation by primary and secondary hemostasis (hemo means blood and stasis means to stop).
The primary hemostasis is the process that characterizes the blood vessels by constriction i.e., vasoconstriction and the aggregation of the platelets at the site of injury.
Secondary hemostasis is the process where the blood flow is arrested from the injured vessel.
The process involves series of factors called coagulation factors that are released and help in the process. The coagulation factors I to XIII are released that initiate and activate the two pathways (intrinsic and extrinsic pathway)
Blood Coagulation Process
Coagulation is complex interaction of anticoagulation factor, pro-coagulation factor and fibrinolytic system. The clotting process involves the following phases;
Clot formation, clot dissolution and clot limitation. Primary hemostasis and secondary hemostasis involve in the activity of clot formation whereas the clot limitation is associated with the antithrombin with protein C and S. Clot dissolution is related with fibrinolysis.
Elements of the hemostasis includes
• Vascular response
• Platelet number
• Platelet function
• Adequate von Willebrand’s factor level
• Adequate clotting factors
Out of which primary hemostasis involves the elements – adequate vascular response, adequate platelet number, adequate platelet function, adequate von Willebrand’s factor level.
Secondary hemostasis includes appropriate adequate amount of clotting factor interaction for the formation of fibrin clot.
a. Primary Hemostasis
It is the process that is responsible for the clot formation with initiation and formation of platelet.
• Injury occurs: The blood vessels at the site constricts and platelet are attracted.
• Then promoting adhesion of these platelets to the sub-endothelium tissue of the injury.
• Platelet form plug by aggregating together and connecting to one other. This is achieved by the von Willebrand’s factor that helps in enhancing the cohesiveness of the platelets.
• There is presence of phospholipid surface on the platelets that provides the factor complexes surface for the proliferation of clot formation.
b. Secondary Hemostasis
This helps in the clot formation with the association of the clotting process via extrinsic and intrinsic cascade.
Coagulation factors released helps in the pathways. The coagulation of blood is either processed by the extrinsic or intrinsic pathway, both resulting in the production of X.
• Extrinsic pathway – extrinsic pathway is generally the first pathway that gets activated in the process in response to protein (tissue factor) which found in the external side of the blood vessels. When injured then the blood from the blood vessels is in the contact of the tissue factor that activates the factor VII that in turn forms the factor VII a, which triggers the series of reaction and which results in production of factor X.
• Intrinsic pathway – it is in contrast to the extrinsic pathway. When the blood vessels are injured then intrinsic pathway is activated by the factor XII – Hageman Factor present in the blood. The blood is circulated and when in contact with injured vessels, it activated the pathway.
• The intrinsic pathway can be activated by the same process of extrinsic pathway. Factor VII a activates factor IX along with the facto X. Factor IX is necessary components for the intrinsic activation. This is the result of cross- activation that helps in the amplification of the coagulation process.
The factor X that is produced helps in the cleavage of prothrombin (factor II) to thrombin (factor II a). Thrombin catalyzes the conversion of fibrinogen (factor I that is soluble plasma protein) to fibrin (insoluble sticky threads).
These thread like fibrin forms the mesh that helps in trapping of platelets, blood cells, plasma. This mesh fibrin network and helps in release fluid content leads to clot retraction that is a durable insoluble that stands the blood flow. This forms the secondary hemostasis of the clotting cascade.
Clotting Limitation and Clotting Dissolution
The antithrombic mechanisms along with the protein C and S are the anticoagulants that leads to the clotting limitation process. Clotting dissolution is under the fibrinolysis (anticoagulation).
Fibrinolysis is influenced by the Plasmin enzyme that helps in dissolving the clot when the bleeding stops. The formed clot is broken down after hours of the formation of the first clot. The hemostasis balance is maintained the fibrinogen with the enzyme plasmin.
Factors are mostly precursor of the proteolytic enzymes known as the zymogens present in the inactive form. The activated form is shown with ‘a’ along with the number. These coagulants (procoagulants or the anticoagulants) are produced in the liver except for the factors III, factor IV, factor VIII.
Prothrombin is formed in liver and is an unstable plasma protein that splits to form the thrombin. Thrombin produced has the pro inflammatory effects which are exerted by the activation by the activation of the protease that is present on the monocytes, lymphocytes, dendritic cells and endothelium.
Factor III or known as TF is membrane bound and procoagulant glycoprotein found in the subendothelial tissue and fibroblast, not exposed or found active until the disruption of the vessels.
Fibrinogen is one of the essential coagulation factors that is produced in the liver and acts as the precursor of the fibrin that makes the strength of the clot. Von Willebrand factor is a glycoprotein found in blood plasma and produced in the megakaryocytes, endothelium and subendothelial connective tissue that helps in the platelet adhesion also helps the factor VIII carrier.
These coagulation factors are classified into three groups-
• Fibrinogen family – This involves the fibrinogen, factor V, factor VIII, factor XIIII
• Vitamin K dependent – this involves the factor II, factor VII, factor IX and factor X
• Contact family – this group includes the factors XI, XII, high molecular weight kininogen, Prekallikerin.
• Hemophilia – this is known to be inherited bleeding disorder. This disorder leads to the continuous blood flow and loss of blood. Hemophilia is observed in people who generally have low levels of clotting factor VIII or factor IX. There are rare cases of hemophilia that might develop in the later stages.
• Congenital fibrinogen deficiency – it is also observed as the inherited genetic disorder that leads to defect of blood clot. This disorder is associated with the protein called fibrinogen. There are cases when there is low level of fibrinogen that leads to the bleeding episodes like nose bleeding or gum bleeding, but the congenital fibrinogen deficiency is the extreme lack of fibrinogen that leads to the complexity of the clot of blood.
These are two of the other major coagulation disorders, the others include – disseminated intravascular coagulation, over-development of circulating anticoagulant, vitamin K deficiency.
The disorders occur due to deficiency of the clotting factors or over production of the factors.
You may like to read;
Blood Coagulation Citations
- Differential Drug Target Selection in Blood Coagulation: What can we get from Computational Systems Biology Models? Curr Pharm Des . 2020;26(18):2109-2115.
- Introduction: blood coagulation. Methods Enzymol . 1993;222:1-10.