1. Damaged Blood Vessels. On vessel injury
HEMOSTASIS
Damaged Blood Vessels.
On vessel injury
Vasoconstriction occurs as a neurogenic response. Injury breaks the smooth endothelial lining, exposing Collagen that promotes thrombus formation by causing the adherence of platelets to the area of injury.
Collagen exposure also initiates the contact phase of coagulation, which begins a series of biochemical reactions known as the Intrinsic coagulation-pathway.
Tissue Thromboplastin is release from the injured vessel, which-promotes coagulation through a different series of reactions known as the Extrinsic pathway.
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2. Vessel wall, Blood flow & Coagulation Substances
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3. In Case if there is an Endothelial Injury (Bleeding must be prevented at site of injury)
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4. Flow must be Maintained
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5. HEMOSTASIS
Primary Hemostasis
Is initiated by the exposure of platelets to the sub-endothelial connective tissue components of blood vessels (collagen, microfilamients, basement membranes).
If acute injury occurs, the small vessels constrict, and platelets immediately adhere to the exposed surfaces and release ADP and ATP.
Thromboxane A also is released, which promotes further Vasoconstriction.
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6. HEMOSTASIS
A reversible primary platelet aggregation takes place during which platelets adhere to one another. Platelets also change shape, and their organelles become centralized. At this point, platelets may disaggregate in the absence of further stimulation. However, with continued stimulation, Secondary, irreversible, platelet aggregation naturally occurs.
Important substances released during platelet aggregation include ADP, ATP, and serotonin. The ADP promotes secondary platelet aggregation and recruits additional platelets to the site of injury. Serotonin promotes further vasoconstriction.
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7. HEMOSTASIS
During aggregation, phospholipid (PL) becomes available on the platelet membrane surface, providing a site for fibrin formation and thrombo-genesis (the formation of blood clots).
Secondary Hemostasis
The Intrinsic and Extrinsic Coagulation Pathways
The intrinsic system is activated in vivo by the contact of certain coagulation proteins with subendothelial connective tissue, which sets the secondary hemostatic mechanism into motion.
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8. HEMOSTASIS
The extrinsic coagulation pathway, in contrast, is initiated with the release of tissue factor from injured vessel endothelial cells and sub-endothelium into the vessel lumen.
Tissue factor, a high-molecular-weight lipoprotein, is found in most organs, including the lungs, kidneys, liver, brain, placenta, and spleen, as well as in large blood vessels such as the vena cava and aorta.
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9. HEMOSTASIS
Both the intrinsic and the extrinsic coagulation pathways lead to secondary hemostasis, namely, the formation of the stable fibrin clot. The clot thus includes both fibrin formed in secondary hemostasis and the platelet plug formed in primary hemostasis.
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10. Hemostatic Plug Formation
Thrombin
AGGREGATION
Fibrin
Hemostatic
clot
Clotting
Platelet Aggregation
0 min
10 min
5 min
SECONDARY
PRIMARY
COAGULATION
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11. HEMOSTASIS
COAGULATION PROTEINS
The intrinsic and extrinsic coagulation pathways are a series of reactions involve coagulation factors known as
1- enzyme precursors (zymogens)
2- non-enzymatic (cofactors)
3- calcium (Ca ++)
4- phospholipids (PL).
All coagulation factors normally are present in the plasma, with PL being provided by platelets.
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12. The zymogens are factors II, VII, IX, X, XI, XII, and prekallikrein
HEMOSTASIS
The zymogens are factors II, VII, IX, X, XI, XII, and prekallikrein
The cofactors are factors V, VIII, tissue factor, and high-molecular-weight kininogen (HMWK).
Zymogens are substrates that have NO biologic activity until converted by enzymes to active enzymes called serine proteases, which have exposed, serine-rich, active enzyme sites.
Serine proteases selectively hydrolyzed arginine or lysine-containing peptide bonds of other zymogens, thus converting them to serine proteases.
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13. COAGGULATION FACTORS
Factor Nomenclature
The nomenclature of coagulation factors covers those referred to by Roman numerals and the two factors in the kinin system, prekallikrein and HMWK, which are referred to by name only.
Each factor was assigned a Roman numeral by the International Committee in Nomenclature of Blood Coagulation Factors in the order of its discovery, not its place in the reaction sequence.
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14. COAGGULATION FACTORS
An important aspect of coagulation factor nomenclature is the “a” that sometimes accompanies a Roman numeral (e.g., factor Xlla). It indicates the activated serine protease form of that factor.
Tissue factor is sometimes referred to as factor III and calcium ions, as factor IV. However, tissue and calcium (Ca++) are the generally accepted terms today.
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15. 2- Prothrombin or vitamin K-dependent group; 3- Fibrinogen group.
COAGGULATION FACTORS
COAGULATION GROUPS
The properties of the coagulation and kinin factors have similarities that can divide these factors easily into three groups:
1- Contact group;
2- Prothrombin or vitamin K-dependent group;
3- Fibrinogen group.
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16. subendothelium in vivo.
COAGULATION GROUPS
Contact Group
Prekallikrein and HMWK of the kinin group along with factors XII and XI, make up the contact group.
The contact group is adsorbed by contact with a negatively charged surface such as collagen or the
subendothelium in vivo.
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17. COAGULATION GROUPS
This contact causes slow conversion of factor XII to XIIa, which initiates both intrinsic system coagulation and fibrinolysis.
Factor XIIa, and HMWK together activate factor XI to XIa, and convert prekallikrein to kallikrein. Kallikrein and HMWK together play a role in intrinsic coagulation activation, activation of fibrinolysis, kinin formation, and activation of the complement system.
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18. Prothrombin (Vitamin K-Dependent) Group
COAGULATION GROUPS
Prothrombin (Vitamin K-Dependent) Group
Contains the vitamin K-dependent coagulation factors
II, VII, IX, and X.
These factors are synthesized in the liver in the presence of vitamin K, which acts as a cofactor.
Vitamin K is fat soluble. It is normally ingested in the diet and also is manufactured by the gut flora. There is no substantial storage of vitamin K in the body.
Vitamin K is necessary to gamma-carboxylate the pre-formed enzyme precursors of factors (II, VII, IX, and X )
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19. (1) dietary vitamin K deficiency;
COAGULATION GROUPS
Vitamin K-dependent gamma-carboxylation reactions may be inhibited by several mechanisms:
(1) dietary vitamin K deficiency;
(2) administration of antibiotics that sterilize the intestinal tract, where normal flora usually synthesize vitamin K;
(3) oral anticoagulant therapy, such as with the coumarin and warfarin drug, which interferes with gamma carboxylation.
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20. COAGULATION GROUPS
Any of these mechanisms can cause the formation of non-functional vitamin K-dependent coagulation factors. When such factors are released to the circulation, they cannot bind to the platelet PL surface and ultimately prevent Prothrombin activation, causing a deficiency in the coagulation pathway.
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21. COAGULATION GROUPS
Fibrinogen Group
The fibrinogen group includes fibrinogen (factor I) and factor V, VIII, and XIII. These have the highest molecular weights of all factors, are the most labile, are consumed in coagulation, and are the only group that act as substrates for the fibrinolytic enzyme plasmin.
Only the factors found in the fibrinogen group are found in the platelets, specifically in the alpha granules with two exceptions: (1) factor XIII is found in the general platelet cytoplasm not in alpha granules, and (2) factor VIII:C, the coagulant portion of factor VIII, is not found in platelets.
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22. COAGULATION GROUPS
PHOSPHOLIPIDS CONTRIBUTING TO COAGULATION
Tissue Factor
The existence of a lipoprotein called Thromboplastin (a complex of two parts, a PL and a protein).
This substance initiates the extrinsic coagulation pathway by binding its PL portion to factor VII, converting factor VII to VIIa.
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23. PHOSPHOLIPIDS CONTRIBUTING TO COAGULATION
The term extrinsic was applied to this pathway because of the necessity of adding a tissue extract (PL) to plasma samples in vitro to initiate and evaluate this coagulation pathway in the laboratory.
The Prothrombin Time (PT) test which evaluates the extrinsic system, is performed using a reagent contained (rabbit brain) or lung tissue Thromboplastin as well as Ca++ to activate factor VII and initiate the extrinsic pathway.
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24. COAGULATION CASCAED
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25. The KININ System
Kinins are peptides of low molecular weight composed of a series of amino acids.
The kinin system contains factors that are activated by the coagulation and fibrinolytic systems.
They mediate inflammatory responses, increase vascular permeability, cause vasodilatation and hypotension.
Important in the contact activation phase of the intrinsic coagulation pathway as in complement activation.
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26. 3- kininogen (low and high molecular weight)
KININ System
The kinin system factors do not have assigned Roman numerals. They include:
1- prekallikrein
2- kallikrein
3- kininogen (low and high molecular weight)
Prekallikrein circulate in plasma as a complex with the cofactor HMWK, and both also are a part of the contact group.
Prekallikrein is converted to the serine protease kallikrein in the presence of factor XIIa and HMWK.
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27. COAGGULATION & The KININ System
Kallikrein accelerates factor XII activation
Also involved in the fibrinolytic system.
Kallikrein and activated XIIa form a complex known as the plasminogen activator which converts plasminogen to its active form, plasmin.
Plasmin is necessary for the degradation of the fibrin clot (fibrinolysis).
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