- Clotting factors: types
- Coagulation factors: production in the body
- Coagulation factors: indications for the test
- Diseases related to clotting factors
- Coagulation factors: therapeutic use
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Clotting factors are primarily proteins that are responsible for the ability of blood to clot. There are as many as a dozen of them and their joint action ensures the maintenance of plasma hemostasis. Under normal circumstances, blood clotting factors prevent blood from leaking out of the blood vessels, but when there are some disturbances in their quantity, patients may experience various symptoms, including bleeding, in this situation.
Coagulation factorsare proteins produced in the liver, whose task is to create a permanent clot and stop the outflow of blood from a damaged blood vessel.
The human body has a number of different mechanisms to maintain its integrity. One of them is hemostasis, which is a process that prevents blood from leaking out of the blood vessel walls. There are generally three types of haemostasis:
The existence of the latter is conditioned by the presence of plasma coagulation factors in the blood.
The most important discoveries about clotting factors and the directly related clotting cascades took place in the 19th and 20th centuries. It was then that other clotting factors were discovered, and at that time scientists were also able to make discoveries about exactly how the blood clotting process works.
In the course of the work, the views on the course of plasma haemostasis were changed many times, but in the end it was possible not only to understand the mechanisms in which clotting factors are involved, but also to learn about their different types and diseases, in which disturbances in the number of individual factors play a role coagulation.
Clotting factors: types
The group of factors influencing clotting sometimes includes different amounts of substances: some authors classify more compounds as clotting factors, and others classify less compounds. The most popular is the classification of plasma clotting factors, which distinguishes 12 of them and they are:
- factor I: fibrinogen (converted to fibrin, which is the basic element of the final clot)
- factor II: prothrombin (responsible - after conversion to thrombin - for the conversion of fibrinogen to fibrin)
- factor III:Tissue thromboplastin (tissue factor)
- factor IV: calcium
- factor V: proaccelerin
- factor VII (proconvertin)
- factor VIII: antihemophilic factor (antihemophilic factor A)
- factor IX: Christmas factor (antihemophilic factor B)
- X factor: Stuart factor
- factor XI: antihemophilic factor C
- factor XII: Hageman factor (contact factor)
- factor XIII: fibrin stabilizing factor
In broader terms than the ones presented above, the group of coagulation factors includes many other substances, among which it is worth mentioning the von Willebrand factor, prekalikreins and proteins C and S.
After analyzing this list, it may be surprising that the factor with the number VI is missing from it. This is not a mistake - in the past, the sixth coagulation factor was distinguished, although in the following years it was not possible to finally confirm its existence. This is why it was deleted from the originally compiled list, to which factor XIII was then added.
Classifications of clotting factors not only assign specific numbers to them, but also a division into labile and stable coagulation factors.
Labile coagulation factors - which include, among others, Factors V and VIII, characterized by the highest lability - are such compounds that can decompose quite quickly (this can happen, for example, in a blood sample taken from a patient).
Stable clotting factors are those that are characterized by a much slower spontaneous decay.
Another division of clotting factors is based on which clotting mechanism the substances activate. Well, there are two so-called coagulation pathways: intrinsic and extrinsic pathways.
The intrinsic coagulation pathway is initiated by the activity of factor XII, while the initiation of the extrinsic pathway is first linked to factors VII, III and IV.
Ultimately, both pathways lead to the activation of a common pathway, which results in the conversion of fibrinogen into fibrin, and this is how a clot is ultimately formed. The entire mechanism by which blood clotting takes place is known as the clotting cascade.
Coagulation factors: production in the body
The production of the clotting factors takes place primarily in the liver. Synthesis (at least some of) of these substances - although to a much lesser degree - also takes place in other parts of the body, such as e.g. megakaryocytes (blood platelet precursors) orendothelial cells.
In general, clotting factors are synthesized in the liver depending on the current needs of the body, but there are some conditions that can affect the production processes of them. You can encounter such a situation, for example, in pregnant women - in pregnancy, clotting factors are synthesized in an increased amount, so in the blessed state there is an increased risk of various thromboembolic events.
While discussing the division of blood coagulation factors, one important aspect has been omitted so far - there are clotting factors dependent on vitamin K and those that are independent of this vitamin.
The first of the above-mentioned cases means that vitamin K is required for the synthesis of given clotting factors. These factors are: II, VII, IX and X. Knowing about it is important not only because it makes you aware of this what problems can vitamin K deficiency lead to.
Awareness of this is used in medicine - when a patient needs to reduce his blood coagulability (as is the case, for example, in patients with atrial fibrillation), he may be given anticoagulants, the action of which may be based on on antagonism towards vitamin K.
Thanks to the use of such preparations, the amount of vitamin K-dependent coagulation factors may be reduced, and thus the expected reduction in blood clotting - examples of this type of drugs are warfarin and acenocoumarol.
Coagulation factors: indications for the test
Tests that indirectly inform about the activity of clotting factors in the body are ordered to patients relatively often. We are talking here about such tests as APTT measurement (which allows to assess the functioning of the intrinsic coagulation pathway), PT (which allows to check the function of the extrinsic coagulation pathway) or INR.
Detecting abnormalities in individual tests may reveal which clotting factors the patient may be deficient in. For example, high INR values suggest that the subject may have a reduced amount of vitamin K dependent clotting factors.
Basically, only when patients show some deviations in the above-mentioned tests and when they are accompanied by some clinical symptoms (such as, for example, a very high tendency to the appearance of bruises or frequent bleeding from various areas, e.g. from the nose ), they are ordered to perform tests to directly assess individual clotting factors.
In these types of situations it is possible to test single, specific clotting factors -Knowing which factor the disorder relates to is very important, because there are different disease entities in which there are disorders regarding the number of separate factors influencing the coagulation process.
Diseases related to clotting factors
The diseases that are possibly most associated with bleeding disorders are hemophilia. A distinction is made between haemophilia A (where the deficiency relates to factor VIII), haemophilia B (where the amount of factor IX is disturbed) and haemophilia C (where the disorder relates to factor XI).
However, a more common disease that is heard less than about hemophiliacs is an entity associated with another clotting factor deficiency - von Willebrand's disease. Still other entities that appear as a result of deficiency of clotting factors include, among others, congenital afibrinogenemia and congenital factor VII deficiency.
It was mentioned earlier that it is the liver that produces the most clotting factors. In a situation where - for various reasons - dysfunction of this organ occurs, they can manifest themselves in different ways, one of them is the disturbance in the production of clotting factors.
For this reason, clotting factors synthesized in the liver - and more precisely, tests that assess their functioning, i.e. APTT and PT - are sometimes ordered to patients with suspected liver dysfunction.
Coagulation factors: therapeutic use
There are situations where a deficiency of clotting factors can even be life-threatening - for example, in patients with disseminated intravascular coagulation syndrome (DIC).
In such a situation - in order to save the patient's life - he may be given coagulation factor preparations. In the case of DIC, vitamin K-dependent coagulation factors are usually administered, and they may also be used in patients with severe liver disease or in those patients who have developed a significant risk of life-threatening bleeding by overdosing with oral anticoagulants.
In the case of other entities that were previously mentioned - such as, for example, haemophilia A or haemophilia B - patients, if necessary, are given preparations of specific clotting factors, the deficiency of which has been found in them.
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2. J. Czajkowska-Teliga, Coagulation disorders in the perinatal period, Perinatology, Neonatology and Gynecology, volume 2, issue 3,208-211, 2009
3. H. Krauss, P. Sosnowski (eds)., Fundamentals of human physiology, Wyd. Scientific University of Poznań, 2009, Poznań, pp. 258-274