Haemostasis is the process of blood flow in the blood vessels and its stopping when the continuity of the blood vessels is interrupted. The goal of haemostasis is therefore to inhibit the formation of blood clots in a he althy bloodstream and to stop bleeding from damaged vessels. What do I need to know about haemostasis? What diseases interfere with hemostasis?
Haemostasisis a complex phenomenon based on the collaboration of various tissues, cells and molecules to maintain a balance between the formation and dissolution of blood clots. Find out about the process of hemostasis and in which diseases it is disturbed.
What is hemostasis?
Hemostasis, i.e. keeping blood in liquid form on the one hand, and preventing bleeding on the other, is a complicated process that takes place constantly in our body. Its proper functioning is based on three main hemostatic systems: vascular, platelet and plasma.
In addition to the clotting system that is activated at the time of vascular damage, the process of fibrinolysis, i.e. the dissolution of blood clots, is also very important.
The balance between clotting and fibrinolysis is the basis for the functioning of hemostasis, and its disturbance may lead to pathological bleeding or thromboembolic diseases.
The process of hemostasis
Imagine a minor cut causing mild bleeding. How is it possible that a few minutes after you cut your wound, the wound stops bleeding? Contrary to appearances, it is a complex and multi-level phenomenon. Its most important stages are:
- Vascular haemostasis
The first immediate response to vessel damage is vasoconstriction. The walls of blood vessels are made of smooth muscle cells, which can significantly constrict their lumen. The blood flow through the contracted vessel is greatly reduced, thus reducing bleeding.
The most important for managing the entire process are the vascular endothelial cells, which line the inside of the vascular system. They perform a number of important functions, such as:
- reaction to vessel damage, transmission of "information" to muscle cells, which then initiate contraction
- release of moleculesactivating and inhibiting clotting
- transmitting a pain signal to nerve fibers, whose task is to reflexively move away from the factor causing the injury
In he althy vessels, the role of the endothelium is to electrostatically "repel" all cells and molecules that might cause a clot to form. This keeps the blood constantly fluid.
At the moment of endothelial damage, a layer of the wall underneath is exposed in the lumen of the vessel, mainly made of collagen. Collagen has the opposite effect on blood flow - it attracts cells to it.
The most important thing from the coagulation point of view is the adhesion of platelets, i.e. thrombocytes, to it. Plates immediately attach to the injury site, thereby initiating the second stage of the clotting process - platelet haemostasis.
- Platelet haemostasis
Thrombocytes, or platelets, are structures with a unique structure. From a biological point of view, they are fragments detached from huge bone marrow cells, called megakaryocytes.
Platelets do not have a nucleus. However, they are perfectly adapted to perform their hemostatic functions: they contain a lot of clotting activators and are ready to release them.
On the outer surface of the cell membrane, they have receptors that allow them to communicate with other cells and molecules, which allows them to fully cooperate with the environment.
As mentioned earlier, the site of endothelial damage becomes very "attractive" to the platelets that immediately accumulate there. Exposed collagen binds to thrombocytes through the so-called von Willebrandt factor.
The attachment of platelets to endothelial cells causes them to interact with each other, which results in the activation of platelets. Activated plates change their shape and release substances stored in their granules.
The most important of them are calcium, magnesium, serotonin, ADP and a whole host of other factors that activate further phases of the clotting process.
Such activated thrombocytes undergo the process of aggregation, i.e. connecting with each other by means of bridges made of fibrinogen. The connected plates form a lamella plug, clogging the damaged area of the vessel. The production of the plug is the last stage of the so-called primary hemostasis.
This is not the end of the clotting process, however, as the platelet plug is not stable enough to prevent possible recurrence of bleeding. It requires additional reinforcement with an insoluble substance - fibrin.The formation of fibrin is the result of the activation of the third stage of the clotting process - plasma hemostasis.
- Plasma haemostasis
Plasma haemostasis is a process in which 13 plasma coagulation factors are involved. These are protein molecules that constantly circulate in the blood. They have a special ability of cascading activation, i.e. a sequence of reactions, enabling the transition of successive factors from inactive to activated form.
There are the so-called the extrinsic and intrinsic pathways of the coagulation cascade. Each of them involves slightly different factors, but their final stage is common.
The final product of both pathways is fibrin, otherwise known as stable fibrin. It is an insoluble substance, made of long, resistant fibers.
Fiber is necessary for the process of secondary hemostasis, i.e. the creation of a strong network that strengthens the primary lamellar plug.
A stabilized platelet-fibrin clot is the final product of the entire clotting process. It guarantees adequate protection against bleeding at the site of injury and allows the damaged vessel to heal.
- Fibrinolysis
An inherent component of hemostasis is the process of fibrinolysis, i.e. dissolution of fibrin. Be aware that fibrinolysis is constantly happening, including in areas where clots are simultaneously forming.
Thanks to fibrinolysis, it is possible to control their size. If blood clots were to grow without restriction, the vessel lumen could be completely occluded and blood flow blocked.
The aim of the fibrinolysis process is therefore to dissolve blood clots in areas of healing wounds and to maintain the fluidity of blood under physiological conditions.
The key substance with the ability to dissolve fibrin and thus also clots is plasmin. This protein molecule is formed, just like fibrin, as a result of the cascade activation of subsequent factors. It is a very complicated process, controlled on many levels by the so-called activators (substances that accelerate fibrinolysis, e.g. tPA, uPA) and inhibitors (substances that inhibit fibrinolysis, e.g. PAI-1, PAI-2).
Activated plasmin has the ability to break down fibrin into short, easily soluble threads. As a result, the blood clot breaks down into fragments of molecules and cells, which are then digested by food cells - macrophages.
Haemostatic disorders
Disturbances in hemostasis processes are the cause of various diseases. We can divide them into 2 main groups: diseases leading to pathological bleeding and diseasesassociated with hypercoagulability.
1. Hemorrhagic flaws
Excessive bleeding tendency, called a hemorrhagic diathesis, can be caused by disorders of vascular, platelet or plasma hemostasis. Most bleeding disorders are congenital, although there are also acquired diseases.
Characteristic symptoms of bleeding disorders are minor skin bruising, bleeding from the gums and epistaxis, excessive traumatic bleeding and (relatively most dangerous) bleeding within internal organs, e.g. gastrointestinal bleeding or vaginal bleeding. The following diseases are distinguished among hemorrhagic disorders:
- Vascular bleeding disorderswhere bleeding tendency is due to abnormal blood vessel structure.
An example of a congenital vascular defect is Rendu-Osler-Weber disease (congenital angioma hemorrhagic), in which easily bleeding hemangiomas develop.
Congenital vascular defects also occur in connective tissue diseases, such as Marfan's syndrome - abnormal structure of connective tissue translates into weakening of the vessel wall, making it more susceptible to damage.
Acquired vascular blemishes can be caused by a variety of factors, resulting in reduced resistance of the vessel walls.
Their most common causes are infections, autoimmune processes (they underlie the so-called Henoch-Schonlein purpura), vitamin deficiencies, drug-induced damage or metabolic disorders. - Platelet bleeding disorderscaused by a reduced number of platelets or a disorder of their function.
A normal platelet count is 150-400,000 / µL. When the platelet count drops below 150,000 / µl, it is called thrombocytopenia. Interestingly, such a condition can remain latent for a long time - usually symptoms of a hemorrhagic diathesis occur only after the platelet count drops below 20,000 / µl.
Thrombocytopenia can be caused by reduced production of thrombocytes in the bone marrow (so-called central thrombocytopenia), or their excessive removal from the bloodstream (peripheral thrombocytopenia).
Central thrombocytopenia is most often associated with congenital or acquired damage to the bone marrow, for example in the course of chemotherapy, cancer, or as a result of certain medications.
Peripheral thrombocytopenia, i.e. the pathological destruction of thrombocytes, most often occurs through the immune mechanism. Platelets are removed from the bloodstream by the cells of the immune system - lymphocytes. Medicines, autoimmune diseases, and infections can cause this condition.
They are slightly differentperipheral non-immune thrombocytopenia. Their example is Moschcowitz syndrome, or thrombotic thrombocytopenic purpura.
In this disease, there is an excessive formation of blood clots in small vessels, which causes wear of the platelets and - as a consequence - symptoms of hemorrhagic diathesis.
Microcoagulation also leads to hypoxia of internal organs, the most dangerous of which is central nervous system hypoxia.
- Plasma hemorrhagic blemishes , caused by a deficiency of plasma coagulation factors. The best known representatives of this group of diseases are haemophilia A and B, i.e. congenital deficiency in the activity of factors VIII and IX, respectively.
The most common congenital plasma diathesis, however, is another disease entity - von Willebrandt disease.
As mentioned earlier, the von Willebrand factor causes the plates to adhere to the wall of the damaged vessel. Its deficiency prevents the formation of the plate plug, which disturbs the entire process of primary hemostasis and leads to pathological bleeding.
One of the acquired causes of clotting factor deficiencies is inadequate dietary intake of vitamin K. It is responsible for the proper concentration of coagulation factor II, VII, IX and X.
2. Hypercoagulant states
Thrombophilia, or states that are excessively prone to blood clots, can have serious consequences. They predispose to the development of venous thromboembolism and arterial thrombosis. Complications of these conditions include thromboembolic changes, such as strokes and heart attacks, as well as obstetric failures.
The causes of thrombophilia are divided - as in the case of bleeding disorders - into congenital and acquired. Examples of congenital thrombophilia are factor V Leiden mutation (most common) and deficiency of substances that inhibit clotting, such as protein C, protein S, or antithrombin.
Acquired thrombophilia can be caused by drugs, immune disorders, and hormonal changes (e.g. during pregnancy or the use of oral contraceptives).
3. DIC Team
The last disease requiring discussion among hemostatic disorders is DIC - disseminated intravascular coagulation syndrome. Its essence is the complete disruption of hemostasis processes - on the one hand, there is a generalized activation of clotting throughout the body, and on the other hand, platelets and plasma coagulation factors are used up, leading to the development of hemorrhagic diathesis.
The result of these disorders are 2 groups of symptoms - the simultaneous formation of multiple clots insmall vessels and bleeding from mucous membranes and internal organs.
Acute DIC is a condition secondary to a number of serious clinical conditions such as sepsis, severe trauma, or multiple organ failure. For this reason, prompt diagnosis and effective treatment of the underlying disease is essential for the treatment of this syndrome.
About the author
Krzysztof BialaziteA medical student at Collegium Medicum in Krakow, slowly entering the world of constant challenges of the doctor's work. She is particularly interested in gynecology and obstetrics, paediatrics and lifestyle medicine. A lover of foreign languages, travel and mountain hiking.
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