From Big Medical Encyclopedia

COAGULANT SYSTEM OF BLOOD (synonym: coagulative system, system of a hemostasis, hemocoagulation) — the enzymatic system providing a stop of bleeding by formation of fibrinny blood clots, maintenance of an integrity of blood vessels and liquid state of blood. The village of the village to. — functional part fiziol. systems regulation of aggregate state of blood (see).

Bases of the doctrine about coagulation blood (see) were developed by A. A. Schmidt. He formulated the theory of a two-phase blood coagulation, according to a cut in the first phase of a blood coagulation as a result of enzymatic reactions is formed thrombin (see), in the second phase under the influence of thrombin fibrinogen (see) turns in fibrin (see). In 1904 Mr. Moravitts (R. O. of Morawitz), then Salibi (V. of S. Salibi, 1952) and Ovren (P. A. Owren, 1954) opened formation of thromboplastins in plasma and showed a role of calcium ions in transformation prothrombin (see) in thrombin. It allowed to formulate the three-phase theory of a blood coagulation, according to a cut process proceeds consistently: in the first phase there is a formation of active prothrombinase, in the second — formation of thrombin, in the third — emergence of fibrin.

According to Makfarlen's scheme a blood coagulation proceeds as the cascade, i.e. there is a consecutive transformation of an inactive factor (proferment) into active enzyme, to-ry activates the following factor. Thus, a blood coagulation — the difficult, multistage mechanism operating by the principle of a feed-back. At the same time in the course of such transformation the speed of the subsequent transformation and amount of the activated substance increases.

Components of plasma, thrombocytes and fabrics participate in the blood coagulation representing enzymatic chain reaction, to-rye are called blood-coagulation factors (see. Hemostasis ). Distinguish plasma (pro-coagulants), fabric (vascular) and cellular (platelet, erythrocyte, etc.) blood-coagulation factors.

The major plasma factors are a factor of I (see. Fibrinogen ), a factor of II (see. Protrombin ), a factor of III, or fabric thromboplastin, a factor of IV, or the ionized calcium, a factor of VII, or Koller's factor (see. Prokonvertin ), factors of V, X, XI, XII, XIII (see. Hemorrhagic diathesis ), factors of VIII and IX (see. Hemophilia ); the factor of III (a thromboplastic factor) — a phospholipoproteid, contains in all body tissues; forms at interaction with a factor of VII and calcium the complex activating a factor of X. Factors of II, V (Expert globulin), VII, IX, X, XI, XII and XIII are enzymes; a factor of VIII (anti-hemophilic globulin — AGG) — a strong aktselerator of clotting enzymes, together with a factor of I it makes not fermental group.

Fabric factors, components of kallikrein-kinin fermental system participate in activation of a blood coagulation and fibrinolysis (see. Kinina ): plasma prekallikrein (Fletcher's factor, factor of XIV) and high-molecular kininogen (Fittsdzherald's factor, Williams's factor, Flodzhek's factor, factor of XV). Villebrand's factor synthesized in an endothelium of vessels, activators and inhibitors belong to fabric factors fibrinolysis (see), prostacyclin — the inhibitor of aggregation of thrombocytes, and also subendobodies and-alnye structure (e.g., collagen) activating a factor of XII and adhesion thrombocytes (see).

Carry group of coagulative platelet factors to cellular factors of blood, from to-rykh thromboxane of Ag (G2 prostaglandin), an erythrocyte analog of a factor of 3 thrombocytes (erythroplates, eritrotsitin), etc. are most important a fosfoligshdny (membrane) factor of 3 thrombocytes (3 tf) and a proteinaceous anti-heparin factor (a factor 4), and also.

Conditionally the mechanism of a blood coagulation can be divided on external (it is started at receipt from fabrics in blood of fabric thromboplastin) and internal (start is carried out at the expense of the fermental factors which are contained in blood or plasma), to-rye to a phase of activation of a factor of X, or a Stuart factor — Prauera, and formations of a protrombinazny complex are carried out to some extent separately with involvement of different factors of coagulation, and afterwards are implemented on the general way. The cascade and complex mechanism of a blood coagulation is presented on the scheme.

Between both mechanisms of a blood coagulation there is complex relationship. So, under the influence of the external mechanism the small amounts of thrombin sufficient only for stimulation of aggregation of thrombocytes, releases of platelet factors, activation of factors of VIII and V are formed that strengthens further activation of a factor of X. The internal mechanism of a blood coagulation is more difficult, but its activation provides massive transformation of a factor of X in a factor Ha and respectively a prothrombin in thrombin. Despite, apparently, important role of a factor XII in the mechanism blood coagulations, at its deficit hemorrhages are absent, there is only a lengthening of a blood clotting time. Perhaps, it is explained by ability of thrombocytes in combination with collagen to activate at the same time factors IX and XI without participation of a factor of XII.

Components of kallikrein-kinin system take part in activation of the initial stages of a blood coagulation, the cut is a stimulator a factor of XII. Kallikrein participates in interaction of factors of XI 1a and XI and accelerates activation of a factor of VII, i.e. carries out a role of a link between internal and external mechanisms of a blood coagulation. The factor of XV takes part in activation of a factor of XI also. At different stages of a blood coagulation difficult proteinaceous and phospholipidic complexes are formed.

Changes and additions are made to a crust, time in the cascade scheme.

Scheme of the cascade and complex mechanism of a blood coagulation

Blood coagulation on the internal mechanism begins with activation of a factor of XII (a factor of contact, or Hageman's factor) at contact with collagen and other components of connecting fabric (at damage of a vascular wall), at emergence in a blood channel of surplus of catecholamines (e.g., adrenaline), proteases, and also owing to contact of blood and plasma with an alien surface (needles, glass) out of an organism. At the same time its active form — a factor HENNA, to-ry together with the factor of 3 thrombocytes which is phospholipid is formed (3 tf), affecting as enzyme a factor of XI, turns it into an active form — factor H1a. Calcium ions do not participate in this process.

Activation of a factor of IX is result of fermental impact of a factor on it H1a, and calcium ions are necessary for formation of a factor 1kha. Activation of a factor of VIII (a factor of Villa) happens under the influence of a factor 1kha. Activation of a factor of X is caused by a complex of factors of IXa, Villa and 3 tf in the presence of calcium ions.

At the external mechanism of a blood coagulation the fabric thromboplastin which came from fabrics and bodies to blood activates a factor of VII and in a complex with it in the presence of calcium ions creates the activator of a factor of X.

The general way of internal and external mechanisms begins with activation of a factor of X — rather stable proteolytic enzyme. Activation of a factor of X accelerates by 1000 times at its interaction with a factor of Va. The Protrombinazny complex which is formed at interaction of a factor Ha with a factor of Va, calcium ions and 3 tf leads to activation of a factor of II (prothrombin) therefore thrombin is formed.

The last phase of a blood coagulation consists in transformation of fibrinogen into the stabilized fibrin. Thrombin — proteolytic enzyme — chips off from alpha and beta chains of fibrinogen at first two peptides A, then two peptides B, as a result remain monomer of fibrin with four free bonds, to-rye then connect in polymer — fibers of not stabilized fibrin. Then with the participation of a factor of XIII (a fibrinstabiliziruyushchy factor) activated by thrombin fibrin is formed stabilized, or insoluble. The fibrinous clot contains many erythrocytes, the leukocytes and thrombocytes which are also providing its consolidation.

So, it is established that not all proteinaceous blood-coagulation factors are enzymes and therefore cannot cause splitting and activation of other proteins. It is established also that at different stages of a blood coagulation complexes of factors are formed, in to-rykh enzymes are activated, and not fermental components accelerate and strengthen this activation and provide specificity of action on substrate. It follows from this that it is reasonable to consider the cascade scheme as cascade and complex. In it the sequence of interaction of various plasma factors remains, but formation of the complexes activating the factors participating in the subsequent stages is provided.

In system of a blood coagulation distinguish also so-called vascular and platelet (primary) and coagulative (secondary) mechanisms hemostasis (see). At the vascular and platelet mechanism occlusion of the damaged vessel by the mass of thrombocytes, i.e. formation of a cellular haemo static stopper is observed. This mechanism provides rather reliable hemostasis in small vessels with low blood pressure. At damage of a vascular wall there is its spasm. The bared collagen and a basal membrane cause adhesion of thrombocytes to a wound surface. Further accumulation and aggregation of thrombocytes in the field of defeat of a vessel with the participation of Villebrand's factor is carried out, there is a reaction of release of platelet blood-coagulation factors, the second phase of aggregation of thrombocytes „a secondary spasm of a vessel, formation of fibrin. The Fib-rinstabiliziruyushchy factor participates in formation of full-fledged fibrin. The important role in formation of platelet blood clot belongs to ADF, under influence a cut in the presence of calcium ions thrombocytes (see) are pasted to each other and form the unit. A source of ADF is ATP of a wall of vessels, erythrocytes and thrombocytes.

At the coagulative mechanism the main role belongs to S.'s factors of page to. Allocation of vascular and platelet and coagulative mechanisms of a hemostasis relatively since both usually function is interfaced. On time of developing of bleeding after influence of the injuring factor it is possible to establish its reason presumably. At defects in plasma factors it arises later, than at thrombocytopenia (see).

In an organism along with mechanisms of a blood coagulation there are mechanisms maintaining liquid state of the circulating blood. According to B. A. Kudryashov's theory, this function is carried out by so-called anticoagulative system, the cut is a fundamental unit the enzymatic and non-enzymatic fibrinolysis providing liquid state of blood in a vascular bed. Other researchers (e.g., A. A. Markosyan, 1972) consider anticoagulative mechanisms a part of uniform coagulant system. S.'s interrelation of page is established to. not only with fibrinolitic system, but also with kininam (see) and system complement (see). The activated factor of XII is for them starting; besides, it accelerates activation of a factor of VII. According to 3. S. Barkagan (1975) and other researchers, as a result of it the factor of XII — kallikreinovy «bridge» between internal and external mechanisms of a blood coagulation begins to function and the fibrinolysis is at the same time activated. The anticoagulative system (anticoagulative system) has the reflex nature. It is activated at irritation of chemoceptors of a circulatory bed owing to emergence in a blood-groove of relative excess of thrombin. Its effector act is characterized by emission in a blood stream heparin (see) and activators of a fibrinolysis from fabric sources. Heparin forms complexes with antithrombin III, thrombin, fibrinogen and some other thrombogenic proteins, and also catecholamines. These complexes have anticoagulating activity, lyse nestabiliziro-bathing fibrin, block in the non-enzymatic way polymerization fibrin-monomer and are antagonists of a factor of XIII. Owing to activation of an enzymatic fibrinolysis a lysis of the stabilized clots is carried out.

The complex system of inhibitors of proteolytic enzymes brakes activity of plasmin, thrombin, kallikrein and the activated blood-coagulation factors. The mechanism of their action is connected with formation of squirrels - proteinaceous complexes between enzyme and inhibitor. 7 inhibitors are revealed: and - a makroglobu-lean, inter - and - inhibitor of trypsin, the Cl-inactivator, alpha 1 - antichymotrypsin, antithrombin III, alpha 2 - anti-plasmin, о^-антитрипсиноним heparin has Immediate anticoagulating effect. The main inhibitor of thrombin is the antithrombin III connecting 75% of thrombin, and also other activated blood-coagulation factors (1kha, Ha, HPA) and kallikrein. In the presence of heparin activity of antithrombin III sharply increases. The globulin which is providing 25% of antithrombic potential of blood and completely suppressing activity of kallikrein is important for a blood coagulation a2 "makr °‘. But the main inhibitor of kallikrein is Cl-inhibitor, to-ry brakes a factor of XII. Antithrombic action also the fibrin, products of proteolytic degradation of fibrin/fibrinogen having antipolimerazny effect on the fibrin and fibrinopeptides which are chipped off from fibrinogen by thrombin possess. Disturbance of activity of S. of page to. high activity of enzyme of plasmin causes (see. Fibrinolysis ).

Blood-coagulation factors contains in an organism much more, than it is necessary for providing a hemostasis. However blood does not turn since there are anticoagulants, and in the course of a hemostasis only a small amount of coagulating factors, napr, a prothrombin, due to self-retardation of hemocoagulation, and also neuroendocrinal regulatory mechanisms is consumed.

Disturbances in S. of page to. can form a basis patol. the processes which are clinically shown in the form of thromboses of blood vessels (see. Thrombosis ), hemorrhagic diathesis (see), and also the accompanying disturbances in system of regulation of aggregate state of blood, napr, trombogemorragichesky syndrome (see), or Machabeli's syndrome. Changes of a hemostasis can be caused by various anomalies of thrombocytes, blood vessels, plasma factors of coagulation or their combination. Disturbances can be quantitative and (or) qualitative, i.e. connected with deficit or excess of any factor, disturbances of its activity or structure, and also with changes of a wall of vessels, bodies and fabrics. They are acquired (influence of toxic chemical connections, infections, ionizing radiation, disturbance of protein, lipidic metabolism, oncological diseases, hemolysis), hereditary or inborn (genetic defects). Among the acquired disturbances leading to deviations in S. page to., the most frequent are thrombocytopenia (see), the functions of marrow connected with oppression, napr, at hypoplastic anemia (see), or with excess destruction of thrombocytes, napr, at Verlgof's disease (see. Werlhof's disease ). Often also meet acquired and hereditary trombotsitopatiya (see), to-rye are result of qualitative defects in a cover of thrombocytes (e.g., deficit of membrane glycoproteins), their enzymes, reaction of release of the thrombocytes leading to disturbance of their ability to aggregation or adhesion, to decrease in maintenance of platelet blood-coagulation factors, etc.

The raised bleeding can develop owing to deficit of blood-coagulation factors or their ingibition specific antibodies. Since many blood-coagulation factors are formed in a liver, at its defeat (hepatitis, cirrhosis) quite often there are hemorrhages caused by decrease in concentration in blood of factors II, V, VII, IX, X or hepatic yew (hypo) fibrinogenemia. Deficit K-vitaminozavisimykh of factors (II, VII, IX, X), followed in some cases by bleeding, it is observed at disturbance of intake of bile in intestines (mechanical jaundice), excess reception of antagonists of phthiocol (coumarins, warfarin), an intestinal dysbiosis, at a hemorrhagic disease of newborns (see. Hemorrhagic diathesis ).

As a result of S.'s activation by the village to., in particular fabric thromboplastins (an operative measure, severe injuries, burns, shock, sepsis, etc.), the full and incomplete disseminated intravascular blood coagulation often develops (see. Trombogemorragichesky syndrome ), the village which is badly giving in to correction, demanding dynamic control of indicators of S. to.

Development of the disseminated blood coagulation and thromboses is promoted by also hereditary or acquired deficit of the main fiziol. anticoagulants, especially antithrombin III, and components of fibrinolitic system. The secondary exhaustion of these substances demanding performing transfusion replacement therapy can be a consequence of their intensive consumption both in the course of a blood coagulation, and at intensive use of the heparin strengthening a metabolization of antithrombin III, the activators of a fibrinolysis (e.g., Streptokinasas) reducing the level of plasminogen in blood.

Disturbances of lipidic exchange and inflammatory processes in walls of vessels lead to structural changes in a vascular wall, organic narrowing of its gleam that can serve as a releaser in formation of blood clot (e.g., at a myocardial infarction). Excess destruction of the erythrocytes containing thromboplastic factors also quite often is premises for formation of blood clots, napr, at a paroxysmal night haemoglobinuria and autoimmune hemolitic anemia (see. Hemolitic anemia ), sickemia (see).

Most often deficit of blood-coagulation factors is caused genetically. So, deficit of factors of VIII, IX, by XI is observed at patients with hemophilia (see). Leads to the raised bleeding deficit of factors of II, V, VII (see. Hypoproconvertinemia ), and also factors of X, XIII and hypofibrinogenemia or afibrinogenemiya (see).

Hereditary functional inferiority of thrombocytes is the cornerstone of big group of diseases, napr, Glantsmann's thrombasthenias, edge is characterized by disturbance of aggregation ability of thrombocytes and retractions of a blood clot (see. Trombotsitopatiya ). The hemorrhagic diathesis proceeding with disturbance of reaction of release of components of granules of thrombocytes or with disturbance of accumulation in thrombocytes of ADF and other stimulators of aggregation (a so-called disease of a pool of accumulation) is described. Quite often trombotsitopatiya are combined with thrombocytopenia (Bernard's disease — Sulye, etc.). Disturbance of aggregation of thrombocytes, defect of granules, decrease in maintenance of ADF are noted at Chediak's anomaly — Higasi (see. Trombotsitopatiya ). Deficit of the plasma proteins participating in processes of adhesion and aggregation of thrombocytes can be the cause of dysfunction of thrombocytes. So, at deficit of a factor of Villebrand adhesion of thrombocytes to a subendothelium and to an alien surface is broken and at the same time coagulative activity of a factor of VIII decreases, one of components to-rogo is Villebrand's factor. At an angiohemophilia — Yurgensa (see. Angiogemophilia ) in addition with these disturbances activity of a fos-folipidny factor of 3 thrombocytes decreases.

Methods of a research C. of page to. are used for clarification of the reasons of bleeding, thromboses and trombogemorragiya. Ability of blood to be curtailed is investigated a series of methods, to-rykh determination of speed of emergence of a blood clot in different conditions is the cornerstone. The most widespread methods having approximate value are establishment blood clotting time (see), a bleeding time (see), a calcium clotting time of plasma and Ovren the thrombotest, to-ry is applied to control of anticoagulating therapy. During the definition of a calcium clotting time of plasma add a distilled water and solution of Calcium chloratum to the studied plasma; fix time of formation of a clot (lengthening of time testifies to tendency to bleeding, shortening — to hypercoagulation). At Ovrena a thrombotest add a reactant to the studied plasma, in Krom all blood-coagulation factors, except factors of II, VII, IX and X contain; the delay of coagulation of plasma testifies to deficit of these factors.

Carry a method of Zigga to more exact methods, with the help to-rogo define tolerance of plasma to heparin, tromboelastografiya (see), methods of definition of thrombin time (see. Thrombin ) and prothrombin time (see), test of generation of thromboplastin, or method of a thromboplastinopoiesis of Biggs Douglas, method of definition kaolin-kefalinovogo of time. At a method of a thromboplastinopoiesis of Biggs — Douglas add the plasma processed by aluminum hydroxide and thrombocytes of the healthy person to the studied serum; the delay of coagulation of plasma at the same time testifies to deficit of blood-coagulation factors. For definition a kaolin-kefalinovogo of time to the studied plasma poor in thrombocytes, add suspension of a kaolin and solution of Calcium chloratum; on time of coagulation of plasma it is possible to establish deficit VIII, IX, XI and XII factors and excess of anticoagulants.

Fibrinolitic activity of blood is defined euglobinovy, gistokhy. by method, etc. (see. Fibrinolysis ). There are additional methods, napr, tests of identification of Cold activation of the kallikreino-vy bridge between factors of XII and VII, methods of definition of products of paracoagulation, physiological anticoagulants, antitromboplasti-new activity, products of degradation of fibrinogen, etc.

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O. K. Gavrilov.