An overview of the Clotting process

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Hemostasis is a complex process that involves multiple interlinked steps. The aim of the cascade is to form a plug that closes the damaged site of the blood vessels, thereby controlling bleeding. It begins with injury in the lining of the blood vessels. The process can be split into four phases, this includes; constriction of the blood vessels, formation of the temporary platelet plug, activation of the coagulation cascade and formation of the fibrin plug or the final clot. There are numerous cells that are involved in the clotting cascade, most notably are the processes associated with the endothelium, platelets and hepatocytes (LaPelusa & Dave, 2020).

Vascular Phase.

Intact blood vessels are central to moderating the blood clotting tendencies. The endothelial cells of the intact vessels prevent the clotting process by expressing a fibrinolytic heparin molecule and thrombomodulin. This prevents platelet aggregation and stopes the coagulation cascade with nitric oxide and prostacyclin. When the blood vessels are cut, the smooth muscles of the blood vessels contract, in the area of the damage. The aim of vascular spasms is to reduce the flow of blood to the area by decreasing the diameter. The cells that line the inside of the blood vessels also contract, to expose the base lamina and the underlying collagen to blood cells. The endothelial wall becomes sticky so that the opposing walls can stick together and stop blood flow. The endothelium also releases hormones and growth factors which causes vascular spasms and induce cell division in the endothelial cells.

Platelet Phase

Thrombocytes stick to the collagen and the basal lamina, as the number of sticky platelets increase, they start to stick to each other forming a platelet plug that can close off the hole of the vessel. Platelet aggregation happens very fast, usually 15 seconds after the damage. The platelets are activated as they arrive at the site and release several factors, such as thromboxane A2 and serotonin (vascular spasm). They release clotting factors PDGF for blood vessel repair and ADP for stimulation and aggregation.  They also release ions for aggregation and clotting, all this happen as a positive feedback mechanism to produce a plug and ultimately a clot.

If the clotting process is unchecked it will continue to happen, but thankfully, we have prostaglandins that will stop the aggregation process. Here we also have inhibitors from the white blood cells as well as plasma enzymes that break down the ADP.

About 30 seconds after injury, the coagulation phase begins. Although a complex process the aim of the coagulation phase is to convert the circulating fibrinogen into fibrin strands, that forms a mesh over the plug. This traps the passing RBC and platelets to form a clot (LaPelusa & Dave, 2020).

Coagulation Phase

If the platelet plug is not enough to stop the bleeding, the third phase of Hemostasis begins. Platelets contain secretory granules. When they stick to the protein in the blood vessel walls, they degranulate. This causes the release of adenosine diphosphate ADP, serotonin, and thromboxane A2 (which activates other platelets). Each of the clotting factors has specific functions. For example, prothrombin is a protein that is produced by the liver. When there is damage to the blood vessels, the nearby platelets are stimulated to release prothrombin activator. The release of prothrombin activator helps activate the prothrombin into an enzyme called thrombin.  Thrombin helps facilitate the conversion of fibrinogen into fibrin (LaPelusa & Dave, 2020).

Intrinsic and Extrinsic clotting pathway. 

Extrinsic is initiated in the blood vessel wall by tissue factor, while intrinsic is in the bloodstream when factors XII contacts collagen fibres.  The two converge in the common pathway when enzymes from either pathway activate X. This forms prothrombinase which is converted into prothrombin and then to thrombin, converting fibrinogen to fibrin.

Clot Resolution

Activated platelets contract their internal actin and myosin fibrils in their cytoskeleton. This leads to shrinkage of the clot volume. Plasminogen then activate plasmin, which promotes breakdown of the fibrin clot. This restores the flow of blood in the damaged vessel.

Clinical note;


This is a condition that is characterised by abnormally low levels of platelets. If the numbers of platelets fall below 50,000, this is a medical emergency, the normal range is between 150,000 to 450,000 platelets per microliter of blood. Thrombocytopenia often occurs as a result of a separate disorder such as leukaemia or immune system-related conditions. Or it can be as a result of taking certain types of medication that have been known to reduce the number of platelets. Some clinical presentations include; easy or excessive bruising (purpura), superficial bleeding into the skin that appears as a rash of pinpoint-sized reddish-purple spots (petechiae), usually on the lower legs and prolonged bleeding from cuts (Thrombocytopenia | National Heart, Lung, and Blood Institute (NHLBI), 2020).

Giant Pletelet Syndrome

This condition happens when the platelets lack the ability to stick adequately to the injured blood vessel walls, this results in abnormal bleeding. The condition usually presents in newborn, infancy or early childhood with bruises, nose bleeds and gum bleeding. later problems may occur with anything that induces bleeding such as menstruation, trauma, surgery or stomach ulcers. This disease is inherited, both parents must carry a gene for the syndrome and then transmit the gene to the child. There is no specific treatment for giant platelet syndrome, bleeding episodes may require transfusion. The abnormal platelets in the syndrome are usually larger than normal platelets. However, this is not the only condition with larger platelets, specific platelet function test, as well as glycoproteins, are required to determine the diagnosis (Giant Platelet Disorder – an Overview | ScienceDirect Topics, 2019).

Gray Platelet Syndrome

This is a rare disorder, about 60 cases have been reported worldwide, individuals with the disorder tend to bruise easily and have increased risk of nosebleeds, or extended bleeding after surgery. They may also experience abnormally heavy bleeding after dental work, or minor trauma.  Women with the condition experience irregular, heavy periods. These bleeding problems are usually mild to moderate, but sometimes they can be life-threatening. A characteristic feature of the condition is myelofibrosis which is the build-up of scar tissue in the bone marrow, the scarring associated with myelofibrosis damages the marrow preventing it from making adequate blood cells. This causes other organs, more specifically the spleen, to start producing more blood cells to compensate, this process may lead to an enlarged spleen (National Library of Medicine, 2020).


Smith, S. A., Travers, R. J., & Morrissey, J. H. (2015). How it all starts: Initiation of the clotting cascade. Critical reviews in biochemistry and molecular biology50(4), 326-336.

Laurino, M., Menara, T., Stella, A., Betta, M., & Landi, A. (2015, August). Procoagulant control strategies for the human blood clotting process. In Engineering in Medicine and Biology Society (EMBC), 2015 37th Annual International Conference of the IEEE (pp. 4439-4442). IEEE.

Giant Platelet Disorder—An overview | ScienceDirect Topics. (n.d.). Retrieved June 1, 2020, from

LaPelusa, A., & Dave, H. D. (2020). Physiology, Hemostasis. In StatPearls. StatPearls Publishing.

Reference, G. H. (n.d.). Gray platelet syndrome. Genetics Home Reference. Retrieved June 1, 2020, from

Thrombocytopenia | National Heart, Lung, and Blood Institute (NHLBI). (n.d.). Retrieved June 1, 2020, from


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