Hemostasis system

HEMOSTASIS SYSTEM HEMOSTASIS SYSTEM Hemostasis is the physiologic Hemostasis is the physiologic

system, which support the blood in system, which support the blood in the fluid condition and prevent the fluid condition and prevent bloodless. bloodless.

Hemostasis system vital necessary Hemostasis system vital necessary and functionally connect with the and functionally connect with the cardiovascular, cardiovascular, digestive, digestive, breathing, breathing, endocrine and other systems. endocrine and other systems.

The components of hemostasisThe components of hemostasis systemsystem

1. 1. The components of hemostasis are The components of hemostasis are - - wall of the vessels, wall of the vessels, - - blood cells – platelets, erythrocytes, blood cells – platelets, erythrocytes, leukocytesleukocytes,, - - enzymes and nonenzymes components of plasma – enzymes and nonenzymes components of plasma –

clotting and anticlotting substances, clotting and anticlotting substances, fibrinolyticfibrinolytic components. components.

2. 2. There are 2 kinds of hemostasisThere are 2 kinds of hemostasis:: vessel-platelets (primary) vessel-platelets (primary) coagulative (secondary)coagulative (secondary)..

PLATELETSPLATELETS Properties and function of plateletsProperties 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 Diameter of platelets is 1-4 micrometers, thickness – 0,5-0,75

micrometers. micrometers. They are the little peace of megakaryocytes cytoplasm (from They are the little peace of megakaryocytes cytoplasm (from

one megacariocytes may develop few hundred of platelets). one megacariocytes may develop few hundred of platelets). Platelets circulates in blood from 5 to 11 days and than Platelets circulates in blood from 5 to 11 days and than destroyed in destroyed in liver, lungs, spleenliver, lungs, spleen by the cells of macrophages by the cells of macrophages system. system. Formation is regulated by thrombopoietin.Formation is regulated by thrombopoietin.

Their granules contain serotonin, Ca2+, 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 Platelets not involved in clotting are kept inactive by Nitric Oxide (NO) and prostaglandins.Oxide (NO) and prostaglandins.

FORMATION OF PLATELETFORMATION OF PLATELET

PlateletsPlateletsactivated platelets

Function of platelets are:Function of platelets are: 1. Haemostatic function – 1. Haemostatic function –

platelets produce substances, platelets produce substances, which are secure the which are secure the hemostasis. hemostasis.

2. Angiotrophic function – 2. Angiotrophic function – provide trophy of provide trophy of endotheliocytes of vessel endotheliocytes of vessel wall, support structure and wall, support structure and functions of micro vessels. functions of micro vessels. These function is realize by These function is realize by adhesion of platelets to adhesion of platelets to endotheliocytes and injection endotheliocytes and injection the enzymes into the the enzymes into the endotheliocytes. For one day endotheliocytes. For one day near 35 G/l of platelets do near 35 G/l of platelets do this function. this function.

Function of platelets are:Function of platelets are: 3. Transport function – 3. Transport function –

transfer the enzymes, transfer the enzymes, ADP, serotonin and other. ADP, serotonin and other.

4. Phagocytes function – 4. Phagocytes function – the contain of platelets the contain of platelets help to kill viruses and help to kill viruses and antigens bodies. antigens bodies.

5. Regeneratory function 5. Regeneratory function – platelets have the – platelets have the growth factor, which help growth factor, which help to grow the endothelial to grow the endothelial and muscles cells which and muscles cells which are present in the vessel are present in the vessel wall.wall.

STAGES OF VESSEL-PLATELETS STAGES OF VESSEL-PLATELETS HEMOSTASISHEMOSTASIS

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 catecholamines and other enzymes. 1 minute is caused by catecholamines 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. Adhesion of platelets – activation of platelets and stick it to 2. Adhesion 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 thrombus which are 3. Reverse aggregation of platelets – the thrombus which are formed may make way for plasma. formed may make way for plasma.

4. Unreverse aggregation of platelets – the thrombus which are 4. Unreverse aggregation of platelets – the thrombus 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.

Primary haemostasisPrimary haemostasis

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

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; 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.

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

VVitamin K (produced by bacteria in the itamin K (produced by bacteria in the colon) stimulates the production of colon) stimulates the production of prothrombin by the liver.prothrombin by the liver.

Clot formation & retractionClot formation & retraction

Fibrinogen

Fibrin Mononer

Fibrin Polymer

Cross LinkedFibrin

Thrombin

F-XIIIa

Blood clotBlood clot

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 prothrombinase. In cases of big from which produced prothrombinase. 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 1.1. Time of clotting by Ly-Wait – 5-10 minutes; Time of clotting by Ly-Wait – 5-10 minutes;

2.2. Time of plasma recalcification – 60-120 seconds; Time of plasma recalcification – 60-120 seconds;

3.3. Thrombotest – IV, V, VI degree; Thrombotest – IV, V, VI degree;

4.4. Thromboplastin time – 12-15 seconds;Thromboplastin time – 12-15 seconds;

5.5. Thromboplastin index – 80-105 %;Thromboplastin index – 80-105 %;

6.6. Concentration of fibrinogen – 2-4 g/L;Concentration of fibrinogen – 2-4 g/L;

7.7. Tolerance of plasma to heparin – 6-11 minutes; Tolerance of plasma to heparin – 6-11 minutes;

8.8. Heparin time – 50-60 seconds;Heparin time – 50-60 seconds;

9.9. Fibrinolysis – 15-20 %.Fibrinolysis – 15-20 %.

Assessment of vascular-platelet hemostasisAssessment of vascular-platelet hemostasis 1. Tests on resistance (fragility) of capillaries. The most 1. Tests on resistance (fragility) of capillaries. The most

commonly used test Konchalovsky-Rhumpel-Leyede. commonly used test Konchalovsky-Rhumpel-Leyede. Evaluation is carried out by the number of Points Evaluation is carried out by the number of Points hemorrhage arising on top of the inner surface of the hemorrhage arising on top of the inner surface of the forearm in a circle with a diameter of 5 cm after 5-minute forearm in a circle with a diameter of 5 cm after 5-minute compression arm cuff at a pressure of 90-100 millimeters compression arm cuff at a pressure of 90-100 millimeters of mercury. Calculation is carried out in 5 minutes after of mercury. Calculation is carried out in 5 minutes after removal of the cuff.removal of the cuff.

2. Samples of the length of capillary bleeding. Sample 2. Samples of the length of capillary bleeding. Sample Duke.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.

Counting the number of plateletsCounting the number of platelets In a blood smear under immersion In a blood smear under immersion

lens erythrocyte count in 1000 lens erythrocyte count in 1000 and that the number of platelets, and that the number of platelets, which are found at the same time. which are found at the same time. Platelet count in 1 liter of blood is Platelet count in 1 liter of blood is determined by the formula:determined by the formula:

х = (а · в) : 100х = (а · в) : 100, where, where x - the number of platelets in 1 x - the number of platelets in 1

liter of bloodliter of blooda - the number of platelets in the a - the number of platelets in the blood smears per 1000 blood smears per 1000 erythrocyteserythrocytesb - the number of red blood cellsb - the number of red blood cells

The normal platelet count is 180-320 g / l.

ThromboelastographyThromboelastography R - time from the beginning of the fluctuations of the cell to the R - time from the beginning of the fluctuations of the cell to the

formation of the first fibrin strands. Characterizes the phase of formation of the first fibrin strands. Characterizes the phase of coagulation.coagulation.

K - the time since the beginning of clot formation to achieve a fixed K - the time since the beginning of clot formation to achieve a fixed level of its density. 3 Displays the phase of blood coagulation.level of its density. 3 Displays the phase of blood coagulation.

MA -maximum amplitude - displays the maximum density of the MA -maximum amplitude - displays the maximum density of the bunch. 80% of the number of MA and properties of platelets (the bunch. 80% of the number of MA and properties of platelets (the ability to aggregate), 20% - the number of formed fibrin.ability to aggregate), 20% - the number of formed fibrin.

Anticoagulative mechanisms. Fibrinolysis.Anticoagulative mechanisms. Fibrinolysis. The primary anticoagulants are The primary anticoagulants are antithrombin III (the most important anticoagulant in antithrombin III (the most important anticoagulant in

the blood); the blood); heparin (heparin (originally found inoriginally found in the liverthe liver, , by large by large

basophilic cells in tissues of various organs. Heparin basophilic cells in tissues of various organs. Heparin reduces the ability of the blood to clot by blocking reduces the ability of the blood to clot by blocking the changethe change 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-2-macroglobulin is a alpha-2-macroglobulin (Alpha-2-macroglobulin is a similar to antithrombin-heparin cofactor in that it similar to antithrombin-heparin cofactor in that it combines with the proteolytic coagulation factors. Its combines with the proteolytic coagulation factors. Its activity is not accelerated by heparin. Its function is activity is not accelerated by heparin. Its function is mainly to act as a binding agent for the coagulation mainly to act as a binding agent for the coagulation factors and prevent their proteolytic action until they factors and prevent their proteolytic action until they can be destroyed in various ways. It a faint inhibitor can be destroyed in various ways. It a faint inhibitor of thrombin, connect with plasmin), of thrombin, connect with plasmin),

alpha-1-antitripsin (Alpha-1-antitripsin inhibits alpha-1-antitripsin (Alpha-1-antitripsin inhibits thrombin activity, IXa, XIa, XIIa factors, plasmin and thrombin activity, IXa, XIa, XIIa factors, plasmin and kallilrein), kallilrein),

protein C (Protein C inhibits VIIIa, Va factors. It protein C (Protein C inhibits VIIIa, Va factors. It activity depend of thrombin and vitamin K 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' aggregation.IXa factor, platelets' aggregation.

FibrinolysisFibrinolysis Clot dissolved by activity of plasmin, an enzyme Clot dissolved by activity of plasmin, an enzyme

which hydrolyzes fibrinwhich hydrolyzes fibrin

System of fibrinolysisSystem of fibrinolysis The composition of fibrinolysis include:The composition of fibrinolysis include:

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

PHASE of FIBRINOLYSISPHASE 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 II phase - conversion profibrinolysis

(plasminogen) in fibrinolysin (plasmin).(plasminogen) in fibrinolysin (plasmin). III phase - splitting fibrin fibrinolysin to III phase - splitting fibrin fibrinolysin to

peptides and amino acids.peptides and amino acids.

Regulation of blood coagulationRegulation of blood coagulationLevels of regulation ofLevels of regulation of

hemostasis:hemostasis:

Molecular Molecular - maintains homeostatic - maintains homeostatic balance of certain factors. This balance of certain factors. This balance always exists between balance always exists between the levels of prostacyclin and the levels of prostacyclin and thromboxane A2, coagulantsthromboxane A2, coagulants

and anticoagulants, activators and and anticoagulants, activators and inhibitors of fibrinolysis.inhibitors of fibrinolysis.

Cells Cells - Provides production factors involved in hemostasis.- Provides production factors involved in hemostasis.OrgansOrgans - providing optimum functioning of the hemostatic - providing optimum functioning of the hemostatic system in different parts of the vascular, the synthesis and system in different parts of the vascular, the synthesis and destruction of its components.destruction of its components.

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