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Secondary haemostasis or coagulation (clotting) mechanismThe primary haemostasis (vascular spasm & platelet plugs) alone is not sufficient to close tears or cuts. When a blood vessel is severely damaged coagulation or blood clotting results in the formation of a clot (a clot is a network of thread like protein fibers called fibrin that traps blood cells, platelets and fluid). some that promote coagulation called procoagulants & others that inhibit coagulation called anticoagulants. Whether or not the blood will coagulate depends on the balance between these two groups of substances.
12 clotting factors was designated with Roman numerals I through XIII as shown in the Table in next plate. All clotting factors are synthesized by the liver, except factor VIII it is synthesized by the endothelial cells of the blood vessels. Factors: II (prothrombin), VII, IX, X& protein C are vitamin K dependant. Deficiency of vitamin K cause deficiency of the above mentioned clotting factors &clotting time is prolonged.It can lead to serious bleeding tendencies.Obstruction of bile ducts or liver diseases cause vit. K deficiency.
Table: system for naming blood-clotting factors.
FactorNames
Arabic Number
Roman number
Fibrinogen
1
I
prothrombin
2
II
Tissue thromboplastin
3
III
Calcium
4
IV
Labile factor
5
V
Stable factor
7
VII
Antihemophilic factor A, classic factor, von-Willebrand factor
8
VIII
Antihemophilic factor B, Christmas factor.
9
IX
Stuart-Prower factor
10
X
Antihemophilic factor C, plasma thromboplastin
11
XI
Hageman factor, glass factor
12
XII
Fibrin-stabilizing factor
13
XIII
High-molecular-weight kininogen
-
HMW-K
Prekalikrein
-
Pre-K
platelet phospholipid , or Platelet factor 3
-
PL , or PF3
Secondary hemostasis consists of a series of biochemical events resulting in the formation of fibrin clot. The clotting mechanism is subdivided into three interacting pathways: 1-The intrinsic pathway. 1-6 minutes 2-The extrinsic pathway.15 seconds in sever tissue truma depend on factors III,, VII& V quantities 3-The common pathway
INTRINSIC PATHWAY
XIْْْْْْْْXIII XIII
Each pathway involves reactions with a specific group of factors. Both the intrinsic & extrinsic systems eventually activate the common pathways influence one another. The clotting mechanism responsible for the formation of fibrin involves a cascade of reactions in which inactive enzymes are activated (a) and the activated enzymes in turn activate other inactive enzymes. The fundamental reaction in the clotting of blood is conversion of the soluble plasma protein fibrinogen to insoluble fibrin.
1. Intrinsic pathway: The intrinsic pathway is named because it begins with chemicals that are inside or intrinsic to the blood. This pathway leading to the activation of Stuart Prower factor (factor X) which in turn leads to conversion of fibrinogen (factor I) into fibrin (clot) in the common pathway. Clotting can occur in 1- 6minutes by intrinsic pathway. 2. Extrinsic pathway: The name extrinsic is derived from the fact that activation of this pathway requires a factor not normally present in the blood but in the most cells of the body. This factor is known as tissue factor or tissue thromboplastin (factor III).
Interaction between extrinsic and intrinsic pathways: a. the end result of both intrinsic and extrinsic pathway is to activate Stuart Prower factor after the blood vessels rupture. B.Clotting is initiated by both pathways simultaneously.C.an important difference between the two pathway that in severe tissue trauma( tissue factor initiates the extrinsic). whereas XII & platelets initiates intrinsic. 3- Common pathway: This is activated by both intrinsic and extrinsic pathways. Intrinsic
IXa, VIIIa; PF3; Ca++ X Xa VIIa, activated tissue factor (IIIa); Ca++; PF3 Extrinsic
The common pathway consists of 5 different steps:1. Activation of Stuart Prower factor by both intrinsic and extrinsic pathways. 2. Formation of prothrombin activator by activated factor X(X a). 3. Conversion of prothrombin (factor II) into thrombin by prothrombin activator. Prothrombin is a plasma protein and α-globulin, & is formed continually by the liver cells. Normal concentration in plasma is 15mg/dL. Vitamin K is required by the liver for normal formation of prothrombin. In liver disease, there is lack of vitamin K that prevents normal prothrombin synthesis can decrease the level of prothrombin in plasma & bleeding tendency results. 4. Conversion of fibrinogen into fibrin by thrombin. 5.stabilization of fibrin
The fibrin (clot) is initially a loose mesh of interlacing strands i.e. the resultant clot (fibrin) is weak & can be broken apart with ease. Activated – stabilizing factor (XIIIa) convert weak soluble fibrin into a dense, stable, insoluble fibrin (clot).
Clot Retraction Within 3-6 minutes after rupture of a blood vessel, if the vessel opening is not too large the entire opening or broken end of the vessel is filled with clot. After 20 minutes to an hour, the clot retracts. Platelets play an important role in the retraction because it contain contractile protein actin & myosin. As the clot condenses, a fluid called serum is squeezed out of it. Serum is plasma from which fibrinogen & some of clotting factors have been removed. Serum cannot clot because of lack of these factors. As the clot retracts, the edges of the broken blood vessels are pulled together, thus possibly contributing to the ultimate state of hemostasis.
Role of calcium in clotting mechanism:. Clotting of blood is prevented by reducing the concentration of Ca++ either by deionizing Ca++ by reacting it with substances such as citrate ions or by precipitating the Ca++ with substances such as oxalate ion ( in vitro ).Vitamin k in clotting mechanism:Deficiencies of vit. K can lead to severe bleeding tendencies and ineffective coagulation. Vit. K is present in many foods, especially green vegetables. Because cow’s milk contain more vit. K than does human milk, breast-fed infants are more susceptible to hemorrhage than bottle-fed infants. Vitamin K deficiency can result in hemorrhages such as frequent nosebleeds.