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Have you ever thought about how our body prevents us from bleeding to death when we get injured? The coagulation cascade is the mechanism in charge of this and just as any other, it is very well regulated in order to respond as soon as a leak is detected.

The coagulation cascade and its main actors 

Bruises and scabs are neither pleasant nor pretty but they are part of a vital mechanism that our body requires to avoid excessive lose of blood after an injury. This mechanism is known as hemostasis or coagulation and its main purpose is to form a blood clot as fast as possible after a tissue, an organ or a blood vessel is damaged. During the process, cells, proteins and other substances participate in the formation of the clot and if any of these components gets disrupted in any way, it can cause severe alterations in the formation of the clot, putting our life at risk.

Platelets, tiny sticky bricks 

Platelets, also known as thrombocytes, are the cells that participate in the coagulation process. These cells do not have a nucleus and are basically just pieces of bigger cells, known as megakaryocytes, that live in the bone marrow. 

Platelets are therefore produced in the bone marrow and when mature, they travel in the circulatory system.

These cells have to fulfill three major functions during coagulation. The first one has to do with their adherence to the blood vessel that has been damaged and has a leak. Their second function is to form a big plug in order to cover the whole damaged area; for this, they attach to other platelets. Their third and final function is to promote the coagulation process by producing small molecules on their surface to activate other molecules that are also part of this mechanism.

These cells do not only participate in the coagulation process, but are also part of the immune system. They interact with other immune cells, such as white blood cells, and they release several substances that promote inflammation.

Coagulation factors: keeping everything together

Apart from the platelets, there are other proteins that participate in the coagulation process.

These proteins are known as coagulation factors and what they basically do is to orchestrate the whole coagulation process.

The platelets are the building blocks that construct the blood clot, but the factors are the builders that control this amazingly organized process.  All of the factors are essential for the whole hemostasis process to take place, but fibrinogen and thrombin are some of the most known ones.

Thrombin is the protein that activates platelets. It binds to the surface of these cells, switching them on and promoting their aggregation to form the clot.

Thrombin also converts fibrinogen into fibrin, which acts like the concrete that keeps platelets together and stabilizes the clot. Without fibrin, platelets would certainly aggregate at the site of injury but they would not be able to stay together by themselves, due to the blood flow pressure.

This process has to be very well balanced in order to avoid the formation of clots when they are not needed and to ensure that if there is a bleeding, the cascade will function properly to avoid massive blood loss. This is why some of the factors promote the formation of the clot, while others inhibit it.

A Coagulation's Cascade Of Events 

The coagulation process is divided into two phases, the primary and the secondary hemostasis. This division is based on the main actors of each phase but both of them happen simultaneously. Let´s see how this works.

Primary hemostasis:The cellular phase 

The main purpose of this phase is to stop the bleeding as soon as possible and avoid more blood loss. It starts with the detection of a rupture in a blood vessel, which can be present in any tissue or any organ.

When a blood vessel is damaged, the inside of its lining gets exposed and gets into direct contact with the blood.

The exposure of a specific protein, known as collagen, and the Von Willebrand coagulation factor start the coagulation process by attaching to the platelets that are traveling at that exact time-point through the bloodstream. Platelets start then to aggregate at the site of the injury and they also start releasing substances that function as messengers, which attract more platelets to the area.

Secondary phase: The coagulation factors phase

At the same time, the coagulation factors start doing their job.

There are 13 coagulation factors that participate in a cascade of messages that promote the stabilization of the already formed platelet aggregate. It is called cascade because factors activate one after the other, in a specific order.

The messages initiate with the activation of the tissue factor and factor VIIa, which activate factor X and convert it into Xa (or X activated). Factor Xa activates prothrombin and converts it into thrombin, which main role is to transform fibrinogen into fibrin. As already said, this last one is the protein that forms a sort of net and attaches platelets between themselves and onto the wall of the blood vessel. Factor XIII stabilizes the fibrin net by doing some final stitches to it. 

Coagulation disorders 

There are many actors in this play and so an alteration to any of them can cause a disruption in the whole process. This is how problems with coagulation arise, giving origin to several diseases.

For example, a low number of platelets or thrombocytopenia, can lead to the formation of bruises and nose bleedings, and can be caused by nutritional deficiencies or even by cancer.

Thrombocytosis on the other hand, refers to an increase in the platelet count and can also be a result of a cancerous process, as well as part of an inflammatory response or as a result of the consumption of certain medications.

Hemophilia is probably one of the most known coagulation related disease.

This is a hereditary health problem, which mainly affects men, and it is caused by a deficiency of either coagulation factor VIII or IX.

Patients with this disease suffer from massive external and internal bleedings and are treated with synthetic factors that promote coagulation when it is needed. Because of this, they need to be very careful and avoid exposure to injuries as much as possible. Probably one of the most famous cases of hemophilia was that of Alexei Romanov, the son of Nicholas II and the last emperor of Russia.

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