Blood coagulation is a process where specific circulating elements in the blood system are converted into a gel with insoluble characteristics; preventing loss of blood from injured blood vessels, tissues, or organs.
The process is made up of two systems.
The first system is around a course that involves the formation of thrombus, a blood clot, through a complicated sequence that involves a cellular system made up of platelets. The platelets can be normally found circulating in the blood for they are mainly involved in the formation of a plug over damaged blood vessels
Another system, the second system, is based on clotting factors acting in concert to form a fibrin clot.
Both the two systems coordinate to form a clot but depend on three important aspects: the clotting factors manufactured in the liver; ionized calcium from the blood; and phospholipids which are components of the platelet membranes (Laposata, M. 2011, p. 11).
Process of Blood Coagulation
Step 1: Injury to blood vessels
Injury to a blood vessel results to exposure of materials that are not normally in direct contact with the flow of blood.
The constituents that are now exposed bring about the adherence of the collagen to the broken surface.
Step 2: Platelet adhesion
Platelets play a key role in blood clotting. Due to injury, platelets in the circulating blood is attracted to the injured surface and starts working to stop the bleeding.
Platelet adhesion happens where platelets bind to specific membrane receptors outside the interrupted endothelium.
The adhesion of platelets to the exposed collagen on endothelial cell surfaces is usually mediated by von Willebrand factor (vWF), a substance synthesized and released from platelets and the endothelium (Robert A.S, Thung.S.L, &John, W., 2002, p. 1). This factor links the platelets to the collagen fibrils.
Step 3: Platelet activation
For hemostasis to occur properly, the platelets must adhere to the exposed collagen, release the contents of the granules, and aggregate.
The process of linking the platelet glycoprotein to the collagen results in the activation of the platelets integrin. Platelets integrin in turn results into the tight binding of the platelets to the extracellular matrix.
Platelets become activated and release stored granules contents into the blood plasma. These include the ADP, vWF, thromboxane, the platelet-activating factor, and serotonin; which in turn activates more platelets in the blood system.
The process in which platelets clump together is known as platelet aggregation.
Step 4: Activation of protein kinase
The contents of the granules activate a protein receptor that is Gq-linked which results into the increased concentration of calcium in the cytosol of the platelets.
The calcium then activates the protein kinase C that later leads to the activation of a specific phospholipase. This phospholipase has the role of modifying the integrin membrane glycoprotein, making it more attracted to fibrinogen.
The cross of links between fibrinogen and the glycoprotein help the adjacent platelets to aggregate, finalising the process of primary hemostasis (Tondre R. &Lebegue, C., 2010, p.41).
Step 5: The conversion of Kallikrein to Kinin
Kallikrein-kinin conversion system is a complex of proteins that when activated leads to the formation of vasoactive kinins.
The kinins are released as a result of the activation of tissue kallikrein or plasma kallikrein. The most important kinin in hemostasis is bradykinin, which is released from high-molecular-weight kininogen (HMWK).
Once the contact system is activated, the blood coagulation cascade is initiated (Robert A.S, Thung.S.L. & John W. 2002, p.1)
Step 6: Blood coagulation cascade
The process of fibrin formation takes place in two different pathways of the coagulation cascade of the secondary hemostasis. The pathways are the contact activation and the tissue factor pathway.
Contact activation pathway (intrinsic pathway)
The step starts with the formation of collagen (Laposata, M. 2011, p. 109).
This step has a minor role in initiating the clot formation process compared to the tissue factor pathway as evidenced by lack of bleeding disorder in patients with severe deficiencies of FXII, prekallikrein and HMWK.
The course is however, much involved in the process of inflammation.
Tissue factor pathway (extrinsic pathway)
This pathway generates the thrombin bust that leads to the release of thrombin from the complex prothrombinase.
Thrombin is a very important component of the coagulation cascade as it activates feedback.
It also activates the other components of the coagulation cascade. The process starts when the blood vessels are damaged (Amy M. K., 2012, p. 1).
Step 7: Activation of prothrombin to thrombin
The final common pathway between the two is the conversion of prothrombin to thrombin.
Whether the coagulation cascade has been activated by the tissue factor or the contact factor pathway, it is maintained in a state that is prothrombotic through the continued activation of both the FIX and FVII.
The process forms the complex tenase, waiting down-regulation by the anticoagulant pathways. The thrombin that has been produced converts fibrinogen to fibrin, forming a mesh with the platelets; plugging the break in the vessel wall.
In addition to its role in the activation of fibrin, thrombin also plays an important role in blood coagulation regulation. It combines with thrombomodulin on endothelial cell surfaces to form a complex, converting protein C to protein Ca (Laposata, M. 2011, p. 129).
Step 8: Control of Thrombin
Excess thrombin would lead to dangerous consequences.
There are two mechanisms of regulating the levels of thrombin in the blood system whenever a blood vessel is damaged.
At each step in the coagulation cascade, feedback mechanisms are required to control the balance between active and inactive thrombin enzymes.
The activation of thrombin is regulated by a number of specific thrombin inhibitors.
Antithrombin III is the most important as it also inhibits the activities of kallikrein, IXa, Xa, XIa and XIIa, and plasmin.
Step 9: Activation of fibrinogen to fibrin
Thrombin leads to the release of the fibrin peptides, which generates fibrin monomers with a sub-unit structure (αβγ)2.
The monomers then spontaneously aggregate in a regular array, forming a weak fibrin clot.
Other than fibrin activation, enzyme thrombin converts XIII to XIIIa, which is a highly specific transglutaminase.
This leads to the introduction of cross-links composed of covalent bonds to the surface of the damaged blood vessel (Amy, M. K., 2012, p.1).
Step 10: Dissolution of the fibrin clot
Dissolution of fibrin clots is the role of plasmin, a serine protease circulating as the inactive pro-enzyme and plasminogen.
Plasminogen binds to fibrinogen and fibrin, incorporated into a clot during formation. Conversion of plasminogen to plasmin leads to the digestion of fibrin, resulting in a soluble degraded product to which neither plasminogen nor plasmin can bind (Antovic, J. P. &Blombäck, M., 2010, P.227).
The immediate process of stopping bleeding after injury is known as hemostasis and involves three events which are: blood vessel spasm, the formation of the platelet plug, and the blood clot formation process; known as blood coagulation.
Clotting of the blood occurs only when thrombin converts fibrinogen to fibrin clot. The clot dissolves eventually by the help of plasmin.
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