Physiology of haemostasis system

Hemostasis systemHemostasis system Hemostasis is very important for our life, Hemostasis is very important for our life,

because if we are live our hemostatic system is because if we are live our hemostatic system is very strong. They are includes in a case of very strong. They are includes in a case of trauma, cutting the vessels etc. Hemostasis istrauma, cutting the vessels etc. Hemostasis is the physiologic system, which support the the physiologic system, which support the blood in the fluid condition and prevent blood in the fluid condition and prevent bloodless. Hemostasis system vital necessary bloodless. Hemostasis system vital necessary and functionally connect with the and functionally connect with the cardiovascular, breathing, endocrine and other cardiovascular, breathing, endocrine and other systems. systems.

The components of hemostasisThe components of hemostasis The components of hemostasis are wall of the The components of hemostasis are wall of the

vessels, blood cells – platelets, erythrocytes, vessels, blood cells – platelets, erythrocytes, leucocytes, enzymes and nonenzymes components of leucocytes, enzymes and nonenzymes components of plasma – clotting and anticlotting substances, plasma – clotting and anticlotting substances, fibrinolysis components of hemostasis. There are 2 fibrinolysis components of hemostasis. There are 2 kinds of hemostasis. They are vessel-platelets kinds of hemostasis. They are vessel-platelets (primary) and coagulative (secondary) hemostasis. (primary) and coagulative (secondary) hemostasis. Primary hemostasis activityPrimary hemostasis activity begin the first after the begin the first after the destroyed of vessels.destroyed of vessels. Secondary hemostasis Secondary hemostasis startsstarts after that in case the primary hemostasis do not after that in case the primary hemostasis do not stopped the bloodlessstopped the bloodless..

Vessel-platelets hemostasisVessel-platelets hemostasis (or primary (or primary hemostasis include in clotting first of all after the hemostasis include in clotting first of all after the

destroyed the safe of vessel wall.)destroyed the safe of vessel wall.) Properties and function of plateletsProperties and function of platelets Quantity of platelets is 180-320 G/L. Diameter of platelets is Quantity of platelets is 180-320 G/L. Diameter of platelets is

1-4 micrometers, thickness – 0,5-0,75 micrometers. They are 1-4 micrometers, thickness – 0,5-0,75 micrometers. They are the little peace of megacariocytes cytoplasm (from one the little peace of megacariocytes cytoplasm (from one megacariocytes may develop few hundred of platelets). megacariocytes may develop few hundred of platelets). Platelets circulated in blood from 5 to 11 days and than Platelets circulated in blood from 5 to 11 days and than destroyed in liver, lungs, spleen by the cells of macrophagal destroyed in liver, lungs, spleen by the cells of macrophagal system. system.

Function of platelets are:Function of platelets are: 1. hemostatic function – platelets produce substances, which 1. hemostatic function – platelets produce substances, which

are secure the hemostasis. 2. Angiotrophic function – provide are secure the hemostasis. 2. Angiotrophic function – provide trophic of endotheliocytes of vessel wall, support structure and trophic of endotheliocytes of vessel wall, support structure and functions of microvessels. These function is realize by functions of microvessels. These function is realize by adgesion of platelets to endotheliocytes and injection the adgesion of platelets to endotheliocytes and injection the enzymes into the endotheliocytes. For one day near 35 G/L enzymes into the endotheliocytes. For one day near 35 G/L platelets do this function. 3. Transport function – transfer the platelets do this function. 3. Transport function – transfer the enzymes, ADP, serotonin and other. 4. Phagocytosis function enzymes, ADP, serotonin and other. 4. Phagocytosis function – the contain of platelets help to kill viruses and antigens – the contain of platelets help to kill viruses and antigens bodies. 5. Regeneratory function – platelets have the growth bodies. 5. Regeneratory function – platelets have the growth factor, which help to grow the endothelial and muscles cells factor, which help to grow the endothelial and muscles cells which are present in the vessel wall.which are present in the vessel wall.

Stages of Stages of vvessel-platelets hemostasisessel-platelets hemostasis 1. Shorting spasm of the vessels – vascular spasm duration to 1. Shorting spasm of the vessels – vascular spasm duration to

1 minute is caused by catecholamins and other enzymes. 1 minute is caused by catecholamins and other enzymes. Diameter of vessels decrease on ½-⅓. Mechanism of it Diameter of vessels decrease on ½-⅓. Mechanism of it development determine by secretion of serotonin and development determine by secretion of serotonin and thromboxan Athromboxan A22 from platelets and epinephrine from ending of from platelets and epinephrine from ending of sympathetic nerves. sympathetic nerves.

2. Adgesion of platelets – activation of platelets and stick it to 2. Adgesion of platelets – activation of platelets and stick it to the place of defect in vessel wall. the place of defect in vessel wall.

3. Reverse aggregation of platelets – the thromb which are 3. Reverse aggregation of platelets – the thromb which are formed may make way for plasma. formed may make way for plasma.

4. Unreverse aggregation of platelets – the thromb which are 4. Unreverse aggregation of platelets – the thromb which are formed can not may make way for plasma. formed can not may make way for plasma.

5. Retraction of platelets plug – decrease the size of plug, pack 5. Retraction of platelets plug – decrease the size of plug, pack down the plug.down the plug.

Investigation of vessel-platelets hemostasisInvestigation of vessel-platelets hemostasis

1. Calculation of the platelets quantity 180-320 1. Calculation of the platelets quantity 180-320 G/L. G/L.

2. Determination of duration of capillary 2. Determination of duration of capillary bleeding after Duke’s method – to 3 minute in bleeding after Duke’s method – to 3 minute in norm. norm.

3. Sample of fragility of capillars – to 10 3. Sample of fragility of capillars – to 10 petechias in norm in a round with diameter 5 petechias in norm in a round with diameter 5 santimetres.santimetres.

Coagulative (secondary) hemostasis.Coagulative (secondary) hemostasis. Characteristics of clotting factors Characteristics of clotting factors There are 12 clotting factors: There are 12 clotting factors: I – fibrinogen; II – prothrombine; III – I – fibrinogen; II – prothrombine; III –

thromboplastin of tissue; IV – ions of calcium; V – thromboplastin of tissue; IV – ions of calcium; V – proaccelerin; VII – proconvertin; VIII – proaccelerin; VII – proconvertin; VIII – antihemophylic factor A; IX – Christmas factor or antihemophylic factor A; IX – Christmas factor or antihemofilic factor B; X – Stuart-Prower factor or antihemofilic factor B; X – Stuart-Prower factor or prothrombinase; XI – plasma thromboplastin prothrombinase; XI – plasma thromboplastin antecedent; XII – Hageman factor; XIII – fibrin antecedent; XII – Hageman factor; XIII – fibrin stabilizing factor. stabilizing factor.

Some of them are enzymes – II, VII, IX, X, Some of them are enzymes – II, VII, IX, X, XI, XII,XIII; otherXI, XII,XIII; other are not – I, III, IV, V, VIII. are not – I, III, IV, V, VIII. The vitamin K is necessary for the functional The vitamin K is necessary for the functional activity of II, VII, IX, X factors.activity of II, VII, IX, X factors.

External mechanism of the first stageExternal mechanism of the first stage (3 factors from the injure (3 factors from the injure tissues go to plasma and interactions with VII factor, the last is tissues go to plasma and interactions with VII factor, the last is activated. VII active factor and IV factors form the complex activated. VII active factor and IV factors form the complex 1a: III + VII active + IV, which is activated X factor.)1a: III + VII active + IV, which is activated X factor.)

Inner mechanism of the first stageInner mechanism of the first stage (Factor 3 of (Factor 3 of platelets – platelets thromboplastine – influence on platelets – platelets thromboplastine – influence on XII factor. Active XII factor + XI is complex 1. XII factor. Active XII factor + XI is complex 1. Active XI factor activated IX factor. Active IX factor Active XI factor activated IX factor. Active IX factor + VIII factor + IV factor is complex 2. Complex 1a + VIII factor + IV factor is complex 2. Complex 1a and 2 are activate X factor. Factor X active + V + IV and 2 are activate X factor. Factor X active + V + IV formed complex 3 or thrombinasa complex.)formed complex 3 or thrombinasa complex.)

Course of the second and third stagesCourse of the second and third stages (The second (The second stage – formation of thrombin from prothrombin. The stage – formation of thrombin from prothrombin. The third stage is formation of fibrin from fibrinogen. The third stage is formation of fibrin from fibrinogen. The last stage has 3 period; formation of fibrin-last stage has 3 period; formation of fibrin-monomers; formation of fibrin S (solubilis); monomers; formation of fibrin S (solubilis); formation of fibrin I (insolubilis). Calcium is formation of fibrin I (insolubilis). Calcium is necessary for all stages.)necessary for all stages.)

Regulation of the clotting mechanismsRegulation of the clotting mechanisms Increase of clotting names hypercoagulation, decrease Increase of clotting names hypercoagulation, decrease

– hypocoagulation. Hypercoagulation may be in a – hypocoagulation. Hypercoagulation may be in a stress cases. It depends on epinephrine, which stress cases. It depends on epinephrine, which concentration increased in the cases of stress. concentration increased in the cases of stress. Epinephrine increase from the vessels walls factors Epinephrine increase from the vessels walls factors from which produced prothrombinasa. In cases of big from which produced prothrombinasa. In cases of big concentration epinephrine should activate XII factor concentration epinephrine should activate XII factor in a bloodstream. It divides fats and fat acids, which in a bloodstream. It divides fats and fat acids, which have prothrombinase activity. After the have prothrombinase activity. After the hypercoagulation stage may be secondary hypercoagulation stage may be secondary hypocoagulation.hypocoagulation.

CoagulogramCoagulogram

Time of clotting by Ly-Wait – 5-10 minutes; Time of clotting by Ly-Wait – 5-10 minutes; time of plasma recalcification – 60-120 time of plasma recalcification – 60-120 seconds; thrombotest – IV, V, VI degree; seconds; thrombotest – IV, V, VI degree; thromboplastin time – 12-15 seconds; thromboplastin time – 12-15 seconds; thromboplastin index – 80-105 %; thromboplastin index – 80-105 %; concentration of fibrinogen – 2-4 g/L; concentration of fibrinogen – 2-4 g/L; tolerancy of plasma to heparin – 6-11 minutes; tolerancy of plasma to heparin – 6-11 minutes; heparin time – 50-60 seconds; fibrinolysis – heparin time – 50-60 seconds; fibrinolysis – 15-20 %.15-20 %.

Anticoagulative mechanisms. Fibrinolysis.Anticoagulative mechanisms. Fibrinolysis. The tendency of blood to clot is balanced by a The tendency of blood to clot is balanced by a

number of limiting reactions that tend to number of limiting reactions that tend to prevent clotting inside the blood vessels and to prevent clotting inside the blood vessels and to break down any clots that do form.break down any clots that do form.

The primary anticoagulants are The primary anticoagulants are antithrombin III (It is the most important antithrombin III (It is the most important

anticoagulant in the blood); heparin (anticoagulant in the blood); heparin (This substance This substance was originally found inwas originally found in the liverthe liver, , by large basophilic by large basophilic cells (mast cells) in tissues of various organs. Heparin cells (mast cells) in tissues of various organs. Heparin reduces the ability of the blood to clot by blocking the reduces the ability of the blood to clot by blocking the changechange of prothrombin to thrombin. It can also be of prothrombin to thrombin. It can also be used to aid in reducing clots in cases in which internal used to aid in reducing clots in cases in which internal clotting has already occurred. clotting has already occurred. HeparinHeparin form complex form complex with antithrombin-III. Activate nonenzyme with antithrombin-III. Activate nonenzyme fibrinolysis.); fibrinolysis.);

alpha-2-macroglobulin, alpha-1-antitripsin, protein C (Alpha-alpha-2-macroglobulin, alpha-1-antitripsin, protein C (Alpha-2-macroglobulin is a similar to antithrombin-heparin cofactor 2-macroglobulin is a similar to antithrombin-heparin cofactor in that it combines with the proteolytic coagulation factors. Its in that it combines with the proteolytic coagulation factors. Its activity is not accelerated by heparin. Its function is mainly to activity is not accelerated by heparin. Its function is mainly to act as a binding agent for the coagulation factors and prevent act as a binding agent for the coagulation factors and prevent their proteolytic action until they can be destroyed in various their proteolytic action until they can be destroyed in various ways. It a faint inhibitor of thrombin, connect with plasmin. ways. It a faint inhibitor of thrombin, connect with plasmin. Alpha-1-antitripsin inhibits thrombin activity, IXa, XIa, XIIa Alpha-1-antitripsin inhibits thrombin activity, IXa, XIa, XIIa factors, plasmin and kallilrein. Protein C inhibits VIIIa, Va factors, plasmin and kallilrein. Protein C inhibits VIIIa, Va factors. It activity depend of thrombin and vitamin K factors. It activity depend of thrombin and vitamin K concentration.concentration.

Functionation of secondary anticlotting Functionation of secondary anticlotting substancessubstances

Primary anticoagulants are produce and Primary anticoagulants are produce and present all time in plasma and secondary present all time in plasma and secondary anticoagulants form in a case of blood clotting. anticoagulants form in a case of blood clotting. They are antithrombin-I or fibrin and products They are antithrombin-I or fibrin and products of fibrinolysis or products of fibrinogen of fibrinolysis or products of fibrinogen degradation. Fibrin is sorbs and inactivates degradation. Fibrin is sorbs and inactivates thrombin and Xa factor. Products of thrombin and Xa factor. Products of fibrinolysis inactivate ending stage of clotting, fibrinolysis inactivate ending stage of clotting, IXa factor, platelets' agregation.IXa factor, platelets' agregation.

THANK YOU!THANK YOU!