1. Hemostasis system

2. HEMOSTASIS SYSTEM Hemostasis is the physiologic system, which support the blood in the fluid condition and prevent bloodless. Hemostasis is the physiologic system, which support the blood in the fluid condition and prevent bloodless. Hemostasis system vital necessary and functionally connect with the cardiovascular, digestive, breathing, endocrine and other systems. Hemostasis system vital necessary and functionally connect with the cardiovascular, digestive, breathing, endocrine and other systems.

5. The components of hemostasis system 1. The components of hemostasis are - wall of the vessels, - wall of the vessels, - blood cells – platelets, erythrocytes, leukocytes, - blood cells – platelets, erythrocytes, leukocytes, - enzymes and nonenzymes components of plasma – clotting and anticlotting substances, fibrinolytic components. - enzymes and nonenzymes components of plasma – clotting and anticlotting substances, fibrinolytic components. 2. There are 2 kinds of hemostasis: vessel-platelets (primary) vessel-platelets (primary) coagulative (secondary). coagulative (secondary).

6. PLATELETS Properties and function of platelets Properties and function of platelets Quantity of platelets is 180-320 G/L. Quantity of platelets is 180-320 G/L. Diameter of platelets is 1-4 micrometers, thickness – 0,5-0,75 micrometers. Diameter of platelets is 1-4 micrometers, thickness – 0,5-0,75 micrometers. They are the little peace of megakaryocytes cytoplasm (from one megacariocytes may develop few hundred of platelets). Platelets circulates in blood from 5 to 11 days and than destroyed in liver, lungs, spleen by the cells of macrophages system. Formation is regulated by thrombopoietin. They are the little peace of megakaryocytes cytoplasm (from one megacariocytes may develop few hundred of platelets). Platelets circulates in blood from 5 to 11 days and than destroyed in liver, lungs, spleen by the cells of macrophages system. Formation is regulated by thrombopoietin. Their granules contain serotonin, Ca 2+, enzymes, ADP, and platelet-derived growth factor (PDGF) Platelets function in the clotting mechanism by forming a temporary plug that helps seal breaks in blood vessels Platelets not involved in clotting are kept inactive by Nitric Oxide (NO) and prostaglandins. Platelets not involved in clotting are kept inactive by Nitric Oxide (NO) and prostaglandins.

7. FORMATION OF PLATELET

8. Platelets Platelets activated platelets

9. Function of platelets are: 1. Haemostatic function – platelets produce substances, which are secure the hemostasis. 1. Haemostatic function – platelets produce substances, which are secure the hemostasis. 2. Angiotrophic function – provide trophy of endotheliocytes of vessel wall, support structure and functions of micro vessels. These function is realize by adhesion of platelets to endotheliocytes and injection the enzymes into the endotheliocytes. For one day near 35 G/l of platelets do this function. 2. Angiotrophic function – provide trophy of endotheliocytes of vessel wall, support structure and functions of micro vessels. These function is realize by adhesion of platelets to endotheliocytes and injection the enzymes into the endotheliocytes. For one day near 35 G/l of platelets do this function.

10. Function of platelets are: 3. Transport function – transfer the enzymes, ADP, serotonin and other. 3. Transport function – transfer the enzymes, ADP, serotonin and other. 4. Phagocytes function – the contain of platelets help to kill viruses and antigens bodies. 4. Phagocytes function – the contain of platelets help to kill viruses and antigens bodies. 5. Regeneratory function – platelets have the growth factor, which help to grow the endothelial and muscles cells which are present in the vessel wall. 5. Regeneratory function – platelets have the growth factor, which help to grow the endothelial and muscles cells which are present in the vessel wall.

11. STAGES OF VESSEL-PLATELETS HEMOSTASIS 1. Shorting spasm of the vessels – vascular spasm duration to 1 minute is caused by catecholamines and other enzymes. Diameter of vessels decrease on ½-⅓. Mechanism of it development determine by secretion of serotonin and thromboxan A 2 from platelets and epinephrine from ending of sympathetic nerves. 1. Shorting spasm of the vessels – vascular spasm duration to 1 minute is caused by catecholamines and other enzymes. Diameter of vessels decrease on ½-⅓. Mechanism of it development determine by secretion of serotonin and thromboxan A 2 from platelets and epinephrine from ending of sympathetic nerves. 2. Adhesion of platelets – activation of platelets and stick it to the place of defect in vessel wall. 2. Adhesion of platelets – activation of platelets and stick it to the place of defect in vessel wall. 3. Reverse aggregation of platelets – the thrombus which are formed may make way for plasma. 3. Reverse aggregation of platelets – the thrombus which are formed may make way for plasma. 4. Unreverse aggregation of platelets – the thrombus which are formed can not may make way for plasma. 4. Unreverse aggregation of platelets – the thrombus which are formed can not may make way for plasma. 5. Retraction of platelets plug – decrease the size of plug, pack down the plug. 5. Retraction of platelets plug – decrease the size of plug, pack down the plug.

12. Primary haemostasis

13. Investigation of vessel-platelets hemostasis 1. Calculation of the platelets quantity 180-320 G/l. 1. Calculation of the platelets quantity 180-320 G/l. 2. Determination of duration of capillary bleeding after Duke’s method – to 3 minute in norm. 2. Determination of duration of capillary bleeding after Duke’s method – to 3 minute in norm. 3. Sample of fragility of capillary – to 10 petechias in norm in a round with diameter 5 centimeters. 3. Sample of fragility of capillary – to 10 petechias in norm in a round with diameter 5 centimeters.

15. Coagulative (secondary) hemostasis. Characteristics of clotting factors Characteristics of clotting factors There are 12 clotting factors: There are 12 clotting factors: I – fibrinogen; I – fibrinogen; II – prothrombine; II – prothrombine; III – thromboplastin of tissue; III – thromboplastin of tissue; IV – ions of calcium; IV – ions of calcium; V – proaccelerin; V – proaccelerin; VII – proconvertin; VII – proconvertin; VIII – antihemophylic factor A; VIII – antihemophylic factor A; IX – Christmas factor or antihemofilic factor B; IX – Christmas factor or antihemofilic factor B; X – Stuart-Prower factor or prothrombinase; X – Stuart-Prower factor or prothrombinase; XI – plasma thromboplastin antecedent; XI – plasma thromboplastin antecedent; XII – Hageman factor; XII – Hageman factor; XIII – fibrin stabilizing factor. XIII – fibrin stabilizing factor.

16. Some of them are enzymes – II, VII, IX, X, XI, XII,XIII; other are not – I, III, IV, V, VIII. The vitamin K is necessary for the functional activity of II, VII, IX, X factors. Some of them are enzymes – II, VII, IX, X, XI, XII,XIII; other are not – I, III, IV, V, VIII. The vitamin K is necessary for the functional activity of II, VII, IX, X factors. Vitamin K (produced by bacteria in the colon) stimulates the production of prothrombin by the liver. Vitamin K (produced by bacteria in the colon) stimulates the production of prothrombin by the liver.

18. Clot formation & retraction Fibrinogen Fibrin Mononer Fibrin Polymer Cross Linked Fibrin Thrombin F-XIIIa

19. Blood clot

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

22. Coagulogram 1. Time of clotting by Ly-Wait – 5-10 minutes; 2. Time of plasma recalcification – 60-120 seconds; 3. Thrombotest – IV, V, VI degree; 4. Thromboplastin time – 12-15 seconds; 5. Thromboplastin index – 80-105 %; 6. Concentration of fibrinogen – 2-4 g/L; 7. Tolerance of plasma to heparin – 6-11 minutes; 8. Heparin time – 50-60 seconds; 9. Fibrinolysis – 15-20 %.

23. Assessment of vascular-platelet hemostasis 1. Tests on resistance (fragility) of capillaries. The most commonly used test Konchalovsky-Rhumpel-Leyede. Evaluation is carried out by the number of Points hemorrhage arising on top of the inner surface of the forearm in a circle with a diameter of 5 cm after 5-minute compression arm cuff at a pressure of 90-100 millimeters of mercury. Calculation is carried out in 5 minutes after removal of the cuff. 1. Tests on resistance (fragility) of capillaries. The most commonly used test Konchalovsky-Rhumpel-Leyede. Evaluation is carried out by the number of Points hemorrhage arising on top of the inner surface of the forearm in a circle with a diameter of 5 cm after 5-minute compression arm cuff at a pressure of 90-100 millimeters of mercury. Calculation is carried out in 5 minutes after removal of the cuff. 2. Samples of the length of capillary bleeding. Sample Duke. 2. Samples of the length of capillary bleeding. Sample Duke. 3. Counting the number of platelets. 3. Counting the number of platelets. 4. Investigation of platelet aggregation ability. 4. Investigation of platelet aggregation ability.

24. Counting the number of platelets In a blood smear under immersion lens erythrocyte count in 1000 and that the number of platelets, which are found at the same time. Platelet count in 1 liter of blood is determined by the formula: In a blood smear under immersion lens erythrocyte count in 1000 and that the number of platelets, which are found at the same time. Platelet count in 1 liter of blood is determined by the formula: х = (а · в) : 100, where х = (а · в) : 100, where x - the number of platelets in 1 liter of blood a - the number of platelets in the blood smears per 1000 erythrocytes b - the number of red blood cells x - the number of platelets in 1 liter of blood a - the number of platelets in the blood smears per 1000 erythrocytes b - the number of red blood cells The normal platelet count is 180-320 g / l.

25. Thromboelastography R - time from the beginning of the fluctuations of the cell to the formation of the first fibrin strands. Characterizes the phase of coagulation. R - time from the beginning of the fluctuations of the cell to the formation of the first fibrin strands. Characterizes the phase of coagulation. K - the time since the beginning of clot formation to achieve a fixed level of its density. 3 Displays the phase of blood coagulation. K - the time since the beginning of clot formation to achieve a fixed level of its density. 3 Displays the phase of blood coagulation. MA -maximum amplitude - displays the maximum density of the bunch. 80% of the number of MA and properties of platelets (the ability to aggregate), 20% - the number of formed fibrin. MA -maximum amplitude - displays the maximum density of the bunch. 80% of the number of MA and properties of platelets (the ability to aggregate), 20% - the number of formed fibrin.

26. Anticoagulative mechanisms. Fibrinolysis. The primary anticoagulants are The primary anticoagulants are antithrombin III (the most important anticoagulant in the blood); antithrombin III (the most important anticoagulant in the blood); heparin (originally found in the liver, by large basophilic cells in tissues of various organs. Heparin reduces the ability of the blood to clot by blocking the change of prothrombin to thrombin. It can also be used to aid in reducing clots in cases in which internal clotting has already occurred. Heparin form complex with antithrombin-III. Activate nonenzyme fibrinolysis.); heparin (originally found in the liver, by large basophilic cells in tissues of various organs. Heparin reduces the ability of the blood to clot by blocking the change of prothrombin to thrombin. It can also be used to aid in reducing clots in cases in which internal clotting has already occurred. Heparin form complex with antithrombin-III. Activate nonenzyme fibrinolysis.);

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

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

30. Fibrinolysis Clot dissolved by activity of plasmin, an enzyme which hydrolyzes fibrin Clot dissolved by activity of plasmin, an enzyme which hydrolyzes fibrin

31. System of fibrinolysis The composition of fibrinolysis include: 1) plasminogen - inactive proteolytic enzyme that is always found in the blood plasma; 2) plasmin - the active form of plasminogen. 3) activators of fibrinolysis - a large group of substances or proteases and are themselves capable of converting plasminogen to plasmin, or causes appearance of these proteases; 4) inhibitors of fibrinolysis. These include protease inhibitors, among which the most important is α2-antiplasmin. The composition of fibrinolysis include: 1) plasminogen - inactive proteolytic enzyme that is always found in the blood plasma; 2) plasmin - the active form of plasminogen. 3) activators of fibrinolysis - a large group of substances or proteases and are themselves capable of converting plasminogen to plasmin, or causes appearance of these proteases; 4) inhibitors of fibrinolysis. These include protease inhibitors, among which the most important is α2-antiplasmin.

32. PHASE of FIBRINOLYSIS In the flow of fibrinolysis are three phases: In the flow of fibrinolysis are three phases: I phase - formation profibrinolysis activators. I phase - formation profibrinolysis activators. II phase - conversion profibrinolysis (plasminogen) in fibrinolysin (plasmin). II phase - conversion profibrinolysis (plasminogen) in fibrinolysin (plasmin). III phase - splitting fibrin fibrinolysin to peptides and amino acids. III phase - splitting fibrin fibrinolysin to peptides and amino acids.

33. Regulation of blood coagulation Levels of regulation of hemostasis: Molecular - maintains homeostatic balance of certain factors. This balance always exists between the levels of prostacyclin and thromboxane A2, coagulants and anticoagulants, activators and inhibitors of fibrinolysis. Cells - Provides production factors involved in hemostasis. Organs - providing optimum functioning of the hemostatic system in different parts of the vascular, the synthesis and destruction of its components.

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