Antykoahulyantы – The system of hemostasis

Physiological anticoagulants, required to maintain blood in a fluid state and process constraints thrombogenesis, They can be divided into two main groups:

1. primary, or independently synthesized and constantly contained in the blood;
2. secondary, formed during proteolysis in blood coagulation and fibrinolysis.

Among the most important primary anticoagulants following inhibitor proteins.

Антитромбин III

Антитромбин III, relating to α₂-globulins and synthesized in the liver, regardless of phylloquinone (Vitamin K), universal inhibitor of nearly all enzymatic coagulation factors - thrombin (IIa), IXa, Far, XIa and XIIa and partly VIIa. It accounts for more 75 % all anticoagulant activity of blood plasma, and the same is the main plasma protein cofactor for heparin.

When inherited or acquired (secondary) reducing antithrombin III there is severe thrombophilic state, characterized by recurrent thrombosis of the main veins of the limbs and internal organs, pulmonary embolism, infarcts of. When the level of antithrombin III below 30 % Patients often die at a young age from thromboembolism, wherein the heparin has no significant their blood anticoagulant action or in experiments in vitro, or when administered intravenously. Hidden tendency to thrombosis there is already at lower levels of antithrombin III below 70-75 %, but in this case thromboembolism develop against other trigger factors (and her pregnancy toxicosis, postoperative period, injuries and considerable physical stress, receiving contraceptive hormones and inhibitors of fibrinolysis and others.).

For a thrombophilia are not only a violation of the synthesis of antithrombin III, and qualitative abnormalities of the protein. In the latter case, there is a much greater reduction of its functional properties, than the amount of antigen protein in blood plasma. In this regard, an important role is played by a parallel study plasma levels of functional activity of antithrombin III has antigen.

Variability also affinity abnormal forms of antithrombin III with heparin, therefore the heparin cofactor activity of blood plasma is often reduced to a greater extent, than the level of antithrombin III, which also indicates the presence of high thrombogenic danger. In this connection of great practical importance is the definition of the properties of the plasma tolerance test via its heparin, and still more particularly via the thrombin-heparin test, t. it is. by the ability of different amounts of heparin extending the study of plasma thrombin time. It should be taken into account, what high blood levels of acute-phase proteins, some of which have a high capacity to bind heparin (eg, a₁-acid glycoprotein), It may also lead to the development of high geparinorezistentnosti. Elevated levels of plasma levels of these proteins, as it is known, naturally occurs in severe inflammatory and destructive processes in the internal organs (including myocardial infarction), as well as in certain malignant tumors. In this connection it is advisable to compare readings thrombin-test with heparin in plasma α₁-acid glycoprotein, C-reactive protein, fibrinogen and fibronectin, and antigeparinovogo factor 4 Platelet.

Recycled reducing antithrombin III in plasma naturally develops in DIC and massive thrombosis (due to intensive spending to neutralize clotting factors), in the treatment of heparin, which activates and accelerates metabolization of antithrombin III, in the early postoperative period, liver diseases, treating L-asparagenazoy and certain other situations. In all these cases there is a risk of secondary thrombosis, and rebound. In this regard, the dynamic control of the level of antithrombin III and geparinorezistentnostyu plasma becomes important clinical significance for assessment of thrombogenic hazards, and for the timely correction of the deficit anticoagulant transfusion of fresh frozen plasma, концентратами антитромбина III, removing from the blood of acute phase proteins (plasmapheresis).

Protein C

Protein C - Synthesized by hepatocytes K-vitaminozavisimy proenzyme (molecular weight 54000- 62000), activated by thrombin (as well as trypsin and Russell's viper venom), after which he acquires the ability to cleave and inactivate the main non-enzymatic boosters clotting process - Factors VIII and V. Activation of this protein is in a complex with a phospholipid C and calcium. The activation process is catalyzed protein C protein formed in the endothelium - trombomodulynom and recently opened another K-factor vitaminozavisimym gepatogennym - proteynom S. Under the influence of protein S are changing the properties of thrombin - drastically weakened its ability to activate factors V and VIII and enhanced its activating effect of these factors on inhibitor - protein C.

Deficiency of protein C It has a value in the clinic. Described his hereditary form, in which patients with childhood or adolescence arose recurrent thrombosis.

Deep secondary inhibition of protein C (until the almost complete disappearance of the blood) observed in acute DIC (rapid clearance of activated thrombin from plasma protein), respiratory distress syndrome, severe liver damage, less significant - in the postoperative period.

Determined protein C and interacting with him all proteins immunologically using specific antisera relevant.

Alpha₂-makrohlobulyn

Alpha₂-makrohlobulyn - Protein, having the ability to bind activated components of blood coagulation and fibrinolysis, disable them from interaction with other factors. Genetically determined deficiency of this protein by itself does not lead to the development of thrombosis, but in combination with other disorders can have pathogenic significance.

In maintaining the liquid state of blood plays an important role group recently opened inhibitor of a tissue thromboplastin - Фактор VIIa (some of them also have anti-Xa activity). This group of inhibitors are inaktivator extrinsic coagulation pathway LACI or EPI), апопротеин A-II и плацентарный антикоагулянтный протеин (PAP).

Secondary physiological anticoagulants formed in the process of blood coagulation and fibrinolysis by further enzymatic changes several coagulation factors, which is why they are after initial activation lose their ability to participate in the process and often hemocoagulation, conversely, acquire properties anticoagulants. Obrazuyushtiysya in svertыvanii adsorbiruet fibrin and thrombin amounts inaktiviruet bolyshie, t. it is. It is both a clotting factor, and anticoagulant (антитромбин I). Products of enzymatic cleavage of fibrinogen fibrin by plasmin (fiʙrinolizinom) inhibit both platelet aggregation, and the formation of fibrin.

In the body, these processes are more complex and sophisticated.

So, adrenaline in complex with fibrinogen and heparin turns out stimulator of platelet aggregation and blood clotting in Factor, preventing blood coagulation in non-enzymatic activator disorganization fibrin (non-enzymatic fibrinolysis).

Pathological anticoagulants

These anticoagulants are missing in the blood under normal conditions,, but it may appear (often in a significant amount) for various immune disorders, less - for no apparent reason.

These include:

• antibodies to coagulation factors, often to VIII and V (usually appear in hemophilia, after delivery and massive blood transfusions);
• immune complexes - Volchanochnyi anticoagulant, violates the initial stages of clotting;
• In антитромбин, often detected in rheumatoid arthritis, and etc.