Definition
Definition
Substance that opposes thrombin.
Classification
We distinguish: 1) Natural antithrombins, the best studied of which is antithrombin III. This is a glycoprotein (protein associated with sugar) produced by the hepatic gland (liver) and which is detected using electrophoresis (application of an electric field to several proteins in a liquid) allowing it to migrate with another variety of proteins: alpha 2 globulins. Antithrombin I (fibrin) has the capacity to absorb and fix significant quantities of thrombin (see below). Antithrombin II is an albumin which is part of the blood plasma (liquid part of the blood) and has the capacity to act as a cofactor of heparin (factor associated with heparin). Antithrombin IV would be close to antithrombin III. Antithrombin V would be a pathological antithrombin. Antithrombin VI appears after the formation of fibrin. Fibrin is an insoluble protein which is mainly involved in the formation of the blood clot. This protein comes from the splitting of fibrinogen (which is the protein precursor of fibrin) obtained under the action of thrombin, during coagulation. 2) Artificial antithrombins, called medicinal, and including indirect thrombin inhibitors such as heparin and heparin derivatives whose action will depend on the presence or absence of antithrombin III to oppose to direct thrombin inhibitors (hirudin and derivatives).
Symptoms
Symptoms
Occurrence of venous thrombosis (swollen, painful, hot or red leg) without a concomitant infection. Personal or family history of venous or arterial thrombosis (pulmonary embolism).
Pathophysiology
In other words, antithrombin is a physiological or pathological substance that allows blood to be anticoagulated. This protein is produced in the liver but also in other organs. The physiological (natural) antithrombins mentioned above act by neutralizing thrombin (the enzyme that causes blood to clot by converting fibrinogen into fibrin). It is essentially antithrombin III that is of interest to discuss. Indeed, this factor is the most active inhibitor of coagulation. Antithrombin also intervenes by potentiating the action of heparin (another physiological anticoagulant). Antithrombin III deficiency is a hereditary condition that is transmitted in an autosomal dominant manner (one of the two parents only needs to carry the genetic anomaly for the offspring to have the disease). For specialists, the mutated gene is located on the 1q23-q25 locus. More recently, three types of deficiency have been distinguished. Type I deficiency is also called quantitative deficiency, type II is called qualitative deficiency and type III is also called abnormality of the antithrombin III binding site on heparin. This last anomaly seems to be little thrombogenic, that is to say not to be the cause of thrombus formation except in individuals inheriting the genetic anomaly from both parents. Antithrombin III deficiency of acquired nature could have repercussions in women who smoke and are also taking the pill. Thrombin is an enzyme whose main action is the transformation of fibrinogen into fibrin. This step is the last in the process of plasma coagulation, that is to say of the liquid part of the blood. To understand the process involving thrombin, it is necessary to know that another protein (prothrombin) is at the origin of thrombin. Indeed, in the presence of vitamin K in the blood, prothrombin, through the intervention of the liver, is synthesized and then activated to give thrombin. This prothrombin is transformed into thrombin thanks to the intervention of another protein called coagulation factor X. This is activated only if there is calcium and another factor called activated factor V in the blood.
Treatment
Treatment
The use of heparin relayed by vitamin K antagonists is necessary. This type of medication is prescribed throughout life in patients with antithrombin deficiency and more particularly in those who have already had an episode of thrombosis. Monitoring by INR examination is the same as for classic venous thrombosis. It is necessary to carry out a family investigation. This leads to proposing prevention (prophylaxis) especially when there is an additional risk of thrombosis occurring, or when we are dealing with a patient wishing to have a means of contraception by estrogen-progestin. Thromboembolic accidents, resulting from this deficiency in antithrombin III can also be prevented by the use of antithrombin III concentrates. This substance is associated with heparin before an intervention in order to maintain an antithrombin III activity level above 80%. This addition of heparin is explained by the fact that the deficiency in antithrombin III is accompanied by a lack of effectiveness of heparin.