FIBRINOLYSIS (fibrin - f-Greek
lysis dissolution, destruction) — the process of dissolution of fibrin which is carried out enzymatic fibrin by lytic system. T. represents a link of anticoagulative system of an organism (see. Coagulant system of the blood) providing preservation of blood in a vascular bed in liquid state.
At F. fibrinolitic enzyme ilazmin, or fibriiolizin (see), splits peptide bonds in molecules of fibrin (see) and fibrinogen (see) therefore fibrin breaks up to soluble fragments in plasma, and fibrinogen loses ability to be curtailed. At F. in the beginning so-called early cleavage products of fibrin and fibrinogen — high-molecular fragments of X and U are formed, and the fragment of X keeps ability to be curtailed iod influence of thrombin (see). Then fragments with a smaller molecular weight (weight) — so-called late cleavage products — fragments and E are formed. Cleavage products of fibrin and fibrinogen possess biol. activity: early cleavage products — the expressed antithrombic action, late, especially a fragment of D — antiioli-merazny activity, ability to slow down aggregation and adhesion of thrombocytes (see), to strengthen action boil it is new (see).
The phenomenon of a fibrineliz was open in 18 century when ability of blood after sudden death was described to remain in liquid state. In a crust, time process F. it is studied at molecular level. The fibrinolitic system consists of four main components: proferment of plasmin — plasminogen, active enzyme — plasmin, fiziol. activators and inhibitors of plasminogen. Most of all plasminogen contains in a blood plasma, from a cut it is besieged together with euglobulina or as a part of
the III fraction at sedimentation of proteins by Kohn's method (see Immunoglobulins). The B to a molecule of plasminogen at operation of activators occurs splitting at least of two peptide bonds and formation of active plasmin. Plasmin has high specificity concerning splitting lysyl-are-gininovykh and lizil-lizinovy bonds in proteinaceous substrates, however substrates, specific to it, are fibrin and fibrinogen. Activation of an ilazminogen in plasmin is carried out as a result of the proteolytic process caused by action of a number of substances.
Fiziol. plasminogen activators are found in plasma and in uniform elements of blood, in excretes (tears, breast milk, saliva, semen, urine), and also in the majority of fabrics. On the nature of action on substrate they are characterized as the argininovy esterases (see) splitting at least one arginil-valinovy communication in a molecule of plasminogen. The following fiziol is known. plasminogen activators: plasma, vascular, fabric, renal or an urokinase, the XII blood-coagulation factors (see. Hemorrhagic diathesis), kallikrein (see Kinina). Besides, activation carry out trypsin (see), Streptokinasa, hundred - a phylokinase. Importance in strengthening F. have the plasminogen activators which are formed in an endothelium of blood vessels. Obrazo
vaniye of plasmin and T. are carried out by the proferment and its activators immobilized (occluded) on a fibrinous clot. Activity F. it is limited to effect of numerous inhibitors of plasmin and its activators. At least 7 inhibitors, or anti-plasmins, partially or completely oppressing activity of plasmin are known. The main physiological quickly operating inhibitor is a2-anti-plasmin, to-ry contains in blood of healthy people in concentration of 50 — 70 mg/l. It suppresses fibrinolitic and esterazny activity of plasmin almost instantly, forming a stable complex with enzyme. High affinity to plasmin defines an important role of this anti-plasmin in regulation of a fibrinolysis of in vivo. The second important inhibitor of plasmin is a2-macroglobulin about a pier. it is powerful (weighing) 720 Ltd companies — 760 000. It biol. function consists in protection of the related plasmin from self-digestion and the inactivating action of others iroteinaz. a2-Antiplazmin and a2-macroglobulin at action on plasmin compete among themselves. Antithrombin III has ability to slowly brake activity of plasmin. Besides, possesses active action о^-анти-трипсин, inter-a2-inhibitor of trypsin, the Cl-inactivator and о^-анти-химотрипсиноним In blood, a placenta, an amniotic fluid are available inhibitors of plasminogen activators: anti-urokinase, anti-asset
of a Torah, anti-Streptokinasa, inhibitor of activation of plasminogen. Existence of a large number of inhibitors of a fibrinolysis is regarded as a form of protection of blood proteins against splitting by their plasmin.
As F. is one of links of anticoagulative system of blood, excitement of chemoceptors of vessels the formed thrombin leads to release in blood of plasminogen activators and bystry activation of proferment. Normal free plasmin in blood is absent or it is connected with anti-plasmins. Activation F. occurs at contagious excitation, a fright, fear, concern, injuries, a hypoxia and a hyperoxia, poisoning of C02, hypodynamia, exercise stresses and at other influences leading to increase in permeability of a vascular wall. At the same time in blood there are high concentration of plasmin causing full hydrolysis of fibrin, fibrinogen and other blood-coagulation factors that leads to disturbance of coagulability of blood. The cleavage products of fibrin and fibrinogen which are formed in blood cause disturbance of a hemostasis (see). Feature F. ability to bystry activation is.
For measurement of fibrinolitic activity of blood use methods of definition of plasmin activity, plasminogen activators and inhibitors — anti-plasmins and anti-activators. Fibrinolitic activity of blood is determined by time of a lysis of clots, plasma or the euglobulin allocated from plasma, by concentration of fibrinogen, lizirovanny in an incubation period, or by number of the erythrocytes which are released from clots. Besides, apply a trombozlastografichesky method (see Tromboelastografiya) and define activity of thrombin (see). The maintenance of plasminogen activators, plasmin and anti-plasmins determine by the sizes of zones of a lysis (the work of two perpendicular diameters) which are formed on fibrinous or fibrin agar plates after putting solutions of euglobulin of plasma on them. The maintenance of anti-activators is defined, at the same time applying Streptokinasa or an urokinase on plates. Esterazny activity of plasmin and activators is established on hydrolysis of chromogenic substrates or nek-ry ethers of arginine and a lysine. Fibrinolitic activity of fabrics is revealed gistokhy. by method by the sizes of zones of a lysis of fibrinous plates after drawing on them thin sections of body or fabric.
Disturbance F. and leads functions of fibrinolitic system to development patol. states. Oppression F. promotes a thrombogenesis (see Thrombosis), to development of atherosclerosis (see), a myocardial infarction (see), a glomerulonephritis (see). Decrease in fibrinolitic activity of blood is caused by reduction in blood of maintenance of plasminogen activators owing to disturbance of their synthesis, the mechanism of release and exhaustion of stocks in cells or increase in amount of anti-plasmins and anti-activators. In an experiment on animals close connection between the maintenance of blood-coagulation factors is established (see. Coagulant system of blood), decrease F. and development of atherosclerosis. At reduced F. fibrin in a vascular bed remains, exposed to lipidic infiltration and causes development of atherosclerotic changes. Fibrin and fibrinogen are found in patients with atherosclerosis in lipidic spots, atherosclerotic plaques. At a glomerulonephritis of adjournment of fibrin are found out in renal balls that it is connected with falloff of fibrinolitic activity of renal fabric and blood.
At oppression F. administer intravenously the drug fibrinolysin (see) and activators of a plazmynogen — Streptokinasa, an urokinase, etc. (see. Fibrinolitic means), the blood increasing fibrinolitic activity causing a lysis of blood clots and their rekanalization (see Thrombosis). This method of conservative treatment of thromboses is theoretically reasonable as a method of imitation of defense reaction of anticoagulative system of an organism against thrombosis. At treatment of thromboses and for the prevention of formation of blood clots F. raise pharmakol. the non-enzymatic connections entered orally; one of them have fibrinolitic effect, braking activity of anti-plasmins, others indirectly cause release of activators of a plazmynogen from an endothelium of vessels. To increase in synthesis of activators F. anabolic steroids promote (see) at their prolonged use and antidiabetic means (see Gipoglike-miziruyushchy means).
Excessive activation F. causes development of hemorrhagic diathesis (see). Allocation in blood of activators of a plazmynogen, formation of a large amount of plasmin promote proteolytic splitting of fibrinogen and blood-coagulation factors that leads to disturbance of a hemostasis.
A number of researchers distinguish primary and secondary raised F. Pervichny raised F. is caused by massive penetration into blood of activators of plasminogen from fabrics that leads to formation of plasmin, to splitting by it V and VII blood-coagulation factors, to hydrolysis of fibrinogen, disturbance of a platelet link of a hemostasis and as a result — to an incoagulability of blood, are a consequence of what fibrinolitic bleedings (see) - Primary general raised F. it can be observed at extensive injuries, disintegration of cells under the influence of toxins, operative measures with extracorporal blood circulation, at an agony, an acute leukosis, and also at hron. myeloleukemia. Primary local raised F. can be the cause of hemorrhages at operative measures, in particular at a prostatectomy, a thyroidectomy, at damage of bodies with the high content of activators of a plazmynogen, uterine bleedings (owing to sharply increased fibrinolitic activity of an endometria). Primary local raised F. can support and strengthen bleeding at a peptic ulcer, injuries of a mucous membrane of an oral cavity, an exodontia, can be the cause of nasal bleedings and a fibrinolitic purpura.
Secondary raised F. develops in response to the disseminated intravascular blood coagulation (see. Hemorrhagic diathesis, Trombogemorragichesky syndrome, t. 29, additional materials). At the same time bleeding arising owing to consumption of blood-coagulation factors amplifies. Differentiation primary and secondary raised F. has practical value. For primary raised F. decrease in content of fibrinogen, plasminogen, inhibitors of plasmin and the normal maintenance of thrombocytes and a prothrombin therefore at it use of inhibitors of a fibrinolysis is shown that it is contraindicated at secondary F is characteristic.
At the bleedings caused raised F., appoint synthetic inhibitors of a fibrinolysis — e-aminokaironovuyu to - that (see. Aminocaproic acid), the para-aminomethylbenzoic to - that (Ambenum), Trasylolum (see) etc. Control of treatment by fibrinolitic drugs and inhibitors of a fibrinolysis is carried out by means of definition of activity of thrombin tromboelastografichesky and other methods characterizing a functional condition of coagulant and anticoagulative systems of blood.
Bibliography: Andreenko G. V. Fibrinolysis. (Biochemistry, physiology, pathology), M., 1979; Biochemistry of animals
and the person, under the editorship of M. D. Kursky,
century 6, page 84, 94, Kiev, 1982; Kudryashov B. A. Biological problems of regulation of liquid state of blood and its coagulation, M., 1975; Methods of a research of fibrinolitic system of blood, under the editorship of G. V. Andreenko, M., 1981; The Fibrinolysis, Modern fundamental and clinical concepts, under the editorship of P. J. Gaffney and S. Balkuv-Ulyutin, lane with English, M., 1982; H elements of E. I. and L of joint stock company and K. M N. Anticoagulants and fibrinolitic means, M., 1977.
G. V. Andreenko.