TROMBYN (synonym of a fibrinogenaz) — the proteolytic enzyme (KF 22.214.171.124) of coagulant system of blood catalyzing hydrolytic decomposition of fibrinogen to fibrin-monomers to-rye will be polymerized in fibrin — a basis of blood clot. T. treats to peptide-hydrolases, a subclass of serinovy proteinases (see Peptide-hydrolase).
A. A. Schmidt established that in the circulating blood T. is in a form of the predecessor — a prothrombin, to-ry turns into T. in the enzymatic way (see the Prothrombin). In the 40th 20 century the first drugs of the USSR cleared by T. V in 1942 were received industrial production of T was mastered. from blood of horses by the B. A method. Kudryashova for use as a local hemostatic at bleedings from parenchymatous bodies.
T. represents a glycoprotein about a pier. it is powerful (weight) apprx. 40 Ltd companies, contains apprx. 5% of carbohydrates. The Pzo-elektrichesky point (see) T. is at pH 7,0 — 7,6. In more alkaline condition and during the strengthening of protein there is its autolysis (see), as a result to-rogo thrombin (and - thrombin) turns in (3-and 7 forms. These forms differ from and - thrombin on structure, have no coagulant activity, keep esterazny, ami-dazny and partially proteolytic activity. Specific inhibitor of T. hirudine is (see), to-ry it is irreversible blocks the site of «recognition» of high-molecular substrates out of an active center. Natural inhibitor T. antithrombin III (a cofactor of heparin) — a glycoprotein about a pier is. it is powerful apprx. 60 000 (see. Hemorrhagic diathesis).
T. represents uzkospetsifichny proteinase. It hydrolyzes the peptide, amide and radio bonds formed by the main amino acids preferential arginine. In the main substrate — fibrinogen (see) — T. hydrolyzes three couples of peptide bonds, releasing fibrinopeptide A (at the same time the fibrin-monomer containing so-called peptide B is formed) and tripeptide. Monomers of fibrin without peptides will quickly be polymerized and stabilized in fibrin (see) a factor of XIII. Monomers with peptides B will be polymerized restrictedly and form high-molecular complexes with fibrinogen — so-called soluble fibrin (see Parakoagulyation, t. 25, additional materials), to-ry appears in blood at nek-ry patol. states, napr, at a syndrome of the disseminated intravascular coagulation (see. Hemorrhagic diathesis), also serves as an indicator of a trombinemiya.
T. causes limited proteo-l from nek-ry factors of coagulant system of blood (see). T. affects blood cells and walls of blood vessels: induces aggregation and
reaction of release of thrombocytes (see), stimulates synthesis of A2 thromboxane by them (see P rostaglandina) and phosphorylation of intracellular proteins; stimulates release of prostacyclin (prostaglandin 12) with cells of an endothelium, synthesis and release of fibronectin (the protein which is available on an outer surface of normal cells); excites specific chemoceptors of a wall of vessels, initiating reflex reaction of anticoagulative system.
T. it is formed of a prothrombin under the influence of a factor Ha (an active Stuart factor — Prauera of the autoprothrombin C) which is in blood in the form of proferment — a factor of X (see the Prothrombin, Coagulant system of blood).
The condition of a final stage of process of a blood coagulation (transformation of fibrinogen into fibrin) reflects thrombin time, a cut is determined by time of coagulation of a blood plasma under the influence of standard solution of thrombin. Normal thrombin time makes 15 — 18 sec. Lengthening of thrombin time can be caused by qualitative or quantitative changes of fibrinogen (see), napr, at a dysfibrinogenemia, at a hypofibrinogenemia (see Afibrinogene-miya), accumulation of products of a fibrinolysis with antipolimerazny activity (see the Fibrinolysis), and also an inactivation of T., napr, at a hyperheparinemia, excess of antithrombins (see. Hemorrhagic diathesis)
what lack of correction of thrombin time at addition to an ispytuyemy blood plasma of fibrinogen testifies to.
For definition of activity of T. several methods are offered. Most often apply a method of definition of time of coagulation of 0,1 — 0,5% of solutions of fibrinogen or a blood plasma the studied solution T. The method of definition of amidazny activity of T is highly sensitive. in relation to highly specific chromogenic substrates — the n-nitroanilides of tripeptides of arginine imitating binding sites of enzyme in a molecule of fibrinogen. About emergence of T. in blood testify increase in maintenance of products of early proteolysis of fibrinogen in it thrombin — fibrinopeptide A and soluble fibrin, decrease in concentration in blood of antithrombin III and detection of its complexes with T., and also emergence of reaction products of release of thrombocytes — a platelet factor 4 and R-trom-boglobulina. The analysis of these data has diagnostic value at a syndrome of the disseminated intravascular coagulation, fibrinferment (see), thromboembolisms (see) etc.
Thrombin as drug. Applied in the medical practician T. receive from plasma of donor blood. In the USSR a method of production receiving the dried-up drug T. from blood of the person it was for the first time developed in 1949 in Leningrad awards of the Labour Red Banner of scientific research institute of hematology and hemotransfusion.
Drug T. (Tbrombinum) represents inodorous white amorphous powder, soluble in isotonic (0,9%) solution of sodium chloride (pH 6,2 — 7,2). In solutions thrombin quickly loses the activity. Besides, T. it is inactivated under influence to - t, alkalis and salts of heavy metals.
Activity of drug is expressed in EA (activity units). For 1 EA accept activity of such number of T., a cut at t ° 37 ° causes coagulation of 1 ml of a fresh blood plasma during 30 sec. or 1 ml of 0,1% of solution of fibrinogen during 15 sec.
On pharmakol. to properties T. treats styptic means (see) local action. During the putting solution of thrombin on the surface of the bleeding fabric there is a bystry fibrillation and film formation of fibrin, edges interferes with bleeding from the damaged small vessels.
T. it is applied to a stop of capillary and parenchymatous bleedings at kidney, liver operations and other parenchymatous bodies, at craniocereberal operations, and also at bleedings, napr, from gums, especially at hypoplastic anemia (see) and Verlgof's diseases (see a Werlhof's disease).
Drug is used locally, dissolving it just before the use in sterile isotonic solution of sodium chloride of room temperature with observance of rules of an asepsis. Impregnate with solutions of drug sterile gauze napkins or an absorbable gelatin sponge, to-rye impose on the bleeding surface. If the wound is closed tightly, the gauze tampon is deleted right after a stop of bleeding. It is necessary to delete a tampon from a wound with care not to damage the formed fib-rinny film and blood clots. In case of treatment of a wound in the open way the tampon can be deleted at the next bandaging. It is possible to leave the absorbable gelatin sponge impregnated with solution of thrombin in a wound since the sponge in it resolves.
Side effect of T. the hl is shown rather seldom. obr. allergic reactions.
T. it is contraindicated at bleedings from large vessels. Solutions of thrombin should not be entered intravenously and intramusculary in order to avoid development of widespread thromboses from the death.
Form of release: the ampoules and bottles with a capacity of 10 ml containing not less than 125 EA of drug. The quantity and activity of drug are specified on ampoules and bottles. Keep in the dry place at a temperature from 2 to 10 °.
Bibliography: Zubairov D. M. Biochemistry of a blood coagulation, M., 1978;
Kudryashov B. A. Biological problems of regulation of liquid state of blood and its coagulation, M., 1975; Laboratory methods of a research of system of a hemostasis, under the editorship of E. D. Goldberg, Tomsk, 1980; Mashkovsky M. D. Pharmaceuticals, p. 2, page 83, M.,
1984; Strukov A. I. and Stru-k about in and S. M. Structurally functional bases of a hemostasis and its pathology, Arkh. patol., t. 42, century 9, page 3, 1980;
Strukova of S. M. Strukturno-funk-tsionalnye of feature of thrombin, in book: Biochemical animals and the person, under the editorship of M. D. Kursky, etc., century 6, page 26, Kiev, 1982; Chemistry and biology of thrombin, ed. bv R. L. Lundblad a. o., Ann Arbor, 1977; ‘Fenton J. W. Thrombin specificity, Ann. N. Y. Acad. Sci., v. 370, p. 468, 1981; The physiological inhibitors of blood coagulation and fibrinolysis, ed. by D. Collen a. o., p. 19, Amsterdam a. o.,
S. M. Strukova; V. K. Muratov (pharm.).