Mechanism of Blood Coagulation :
Introduction :- Mechanism of Blood Coagulation
Blood that has been shed becomes semisolid jelly and loses its mobility in a matter of minutes. We refer to this process as clotting or coagulation. When the clot is kept for longer, it folds down to a lesser amount and secretes a clear fluid known as the serum. Serum will no longer clot. Under an ultrasonic microscope, the coagulation process is observed to begin with the appearance of tiny granules, frequently in the vicinity of a cluster of dissolving platelets. These granules come combine to create needles, and then those needles combine once more to form long threads that crisscross the majority of the blood. The red and white cells become entangled in the meshes of this network, which is formed by the crossing of these threads. Gradually, the clot recedes and the serum separates.
Importance of Mechanism of blood Coagulation :-
The physiological significance of the coagulation phenomena cannot be overstated. Its goal is to halt more bleeding. When bleeding happens, the blood that is lost clots and blocks the bleeding vessels. The bleeding is halted when the clot retracts because it compresses the broken vessels even more.
Both primary and secondary hemostasis are involved in the coagulation phenomena.
Primary hemostasis: – The platelet forms a platelet plug by adhering to the vascular wall; this stage of the process is referred to as primary hemostasis.
Secondary hemostasis: Definitive hemostasis is the creation of a fibrin clot through the combination of clotting factor with the help of enzymatic processes.
Phases of Mechanism of blood Coagulation :-
Blood coagulation typically happens in three phases:
1. Prothrombin activator formation
2. Prothrombin’s conversion to thrombin
3. Fibrinogen conversion to fibrin.
Phase 1. Prothrombin activator formation :-
Prothrombin activator, a material that changes prothrombin into thrombin, is formed at the start of blood coagulation. Things created either outside or inside the blood begin the process of its creation.
The intrinsic pathway, the extrinsic pathway, and the common pathway are the three essential ways that make up this process.
1. Intrinsic Pathway
Disruption to the bloodstream vessel wall and protein exposure start the intrinsic route. It involves multiple clotting factors that are already in the blood, including XII, XI, IX, and VIII.
Reaction Cascade- i. The blood vessel is ruptured during the injury. Collagen beneath the endothelium is visible due to endothelial deterioration.
ii. Factor XII, also known as Hageman factor, is transformed into activated factor XII when it comes into contact with collagen in the presence of kallikrein and high molecular weight (HMW) kinogen.
iii. In the presence of HMW kinogen, activated factor XII transforms factor XI into activated factor XI.
iv. When factor IV (calcium) appears, the active factor XI stimulates factor IX.
v. When the factors VIII and calcium are present, engaged factor IX activates factor X.
vi. Platelets become activated and release phospholipids when they come into contact with the collagen of a broken blood artery.
vii. At this point, active factor X combines with factor V and platelet phos pholipid to create prothrombin activator. Calcium ions must be present for this to happen.
viii. The helpful feedback effect of thrombin also activates Factor V.
2. Extrinsic Pathway
This process includes the synthesis of tissue thromboplastin from injured tissues, which triggers the synthesis of prothrombin activator.
Reaction Cascade- i. Damaged tissues experience the tissue’s (factor III) release. Phospholipid and glycoprotein, two proteins found in thromboplastin, work as proteolytic enzymes.
ii. In the presence of factor VII, the glycoprotein and phospholipid components that make thromboplastin alter factor X into actuated factor X.
iii. Prothrombin activator is created when enacted calculate X combines with tissue thromboplastin’s phospholipid component and factor V. The presence of calcium particles is essential for this process.
3. Common Pathway :-
The intrinsic and extrinsic pathways come together when Factor X is activated.
Formation of Prothrombin Activator:
Phospholipids, calcium particles (Ca2+), activated Calculate X (X a), and Calculate V form the prothrombin activator complex. This complex converts prothrombin (Factor II) to thrombin (Factor IIa).
Phase 2. Prothrombin's conversion to thrombin :-
The production of thrombin is essential to blood coagulation. Clot formation is unquestionably triggered by the production of thrombin.
Reaction Cascade- i. Within the presence of calcium, prothrombin is converted into thrombin by prothrombin activator, which is produced in both intrinsic and extrinsic pathways (factor IV).
ii. After forming, thrombin triggers the synthesis of further thrombin molecules. Factor V is activated by the thrombin that was first produced. The production of intrinsic and extrinsic prothrombin activator, which changes prothrombin into thrombin, is accelerated by factor V. Positive feedback effect is the name given to this thrombin effect.
Phase 3. Fibrinogen conversion to fibrin. :-
The last step of blood clotting is the thrombin-mediated conversion of fibrinogen to fibrin.
Reaction Cascade- i. Thrombin causes the loss of two sets of polypeptides from every fibrinogen molecule, converting inactive fibrinogen into activated fibrinogen. Fibrin monomer is the name for the activated fibrinogen.
ii. The monomer of fibrin becomes polymerized with different monomer molecules to create strands of fibrin that are loosely organized.
iii. Later, in the occurrence of calcium ions, fibrinogen-stabilizing factor (factor XIII) modifies these loose strands into thick and tight fibrin threads. A stable clot is formed by the aggregation of all the compact fibrin strands.
Factors involve in Mechanism of blood Coagulation :-
Certain blood proteins called blood clotting factors work together to form blood clots and prevent excessive bleeding if a blood vessel is damaged. These components are part of a complex cascade called the coagulation cascade, which consists of a series of phases in which each component activates other components within a specific group.
FACTORS :- Mechanism of Blood Coagulation
Factors I – Fibrinogen
Factors II – Prothrombin
Factors Ill – Tissue factors or Thromboplastin
Factors IV – Calcium
Factors V – Proaccelerin (labile factor )
Factors VII- Stable factor
Factors VIII- Antihaemophilic factor A
Factors IX – Antihaemophilic factor B ( plasma thromboplastin factor or Christmas factor )
Factors X – Stuart prower factor
Factors XI – Plasma thramboplastin antecedent
Factors XII – Hageman factor
Factors XIII – Fibrin stablising factor
Factors I - Fibrinogen :-
1. Although it is essentially a globulin, the molecule is much larger than serum globulin. Its molecular weight is about 33,000.
2. At about 56 °C, ammonium sulfate and one-fifth of the NaCl saturation amount coagulate and precipitate.
3. Its ability to cause blood clotting, a process in which fibrinogen is converted to fibrin, distinguishes it from other plasma proteins.
Factors II - Prothrombin :-
1. It is a type of protein that can be found in human plasma.
2. It possesses a molecular weight of about 62,700.
3. In an aqueous solution, it is highly unstable and deactivated by heat at 60 °C, basic at pH 10, and acids at pH 4.8. On the other hand, once released from the frozen form, it remains stable forever. (A liquid’s pH level indicates how many hydrogen ions (H-) are present. The blood typically has a pH of 7.35 to 7.45.)
4. Oxalated plasma contains two types of prothrombin: “A” and “B”. Oxygen destroys the “A” form, and it is unstable to heat. Aluminum hydroxide can be used to eliminate the “B” form. The two forms stay linked together as calcium compounds in normal plasma.
5. The addition of oxalate causes the calcium to be eliminated, separating the two substances.
6. The prothrombin activity of blood is determined by measuring the clotting time of tissue emulsion added to recalculated oxalated plasma.
7. The average ‘prothrombin time’ in human subjects is 12 seconds. If you are lacking in Stuart factor, factor VII, or factor V, your prothrombin time will be longer.
8. The liver is where prothrombin is made. Vitamin K is necessary for prothrombin synthesis. Prothrombin is changed into thrombin during the clotting process.
Factors Ill - Tissue factors or Thromboplastin :-
Factors such as Hageman factor (factor XII), PTA (factor XI), Christmas factor (factor IX), antihemophilic globulin (factor VIII), calcium ions, factor V, and factor V. In the presence of calcium ions, endogenous thromboplastin helps convert prothrombin to thrombin. Note that if blood flows normally through the circulatory system, it will not clot. However, even in the absence of tissue extracts (exogenous thromboplastin), blood will clot if the surface of the blood vessels is roughened for some reason.
It is created from a variety of tissues, such as damaged brain, lung, or other tissue components. It was previously understood that prothrombin was changed into thrombin by the action of calcium ions and thromboplastin that was freed from injured tissues. However, it has recently been discovered that different plasma factors—such as proconvertin or factor VII—are necessary for this conversion, which is known as extrinsic thromboplastin production.
Factors IV - Calcium :-
Ionic calcium functions as an additional component in the coagulation process, which makes it necessary for blood clotting. It is necessary for prothrombin’s conversion to thrombin as well as the production of extrinsic and intrinsic thromboplastins.
Factors V - Proaccelerin (labile factor ) :-
This component is required for the extrinsic or intrinsic thromboplastin to fully convert prothrombin into thrombin. This protein is heat-labile and can be activated in 30 minutes at 56°C or by raising the pH to 10.5 levels. Although it appears in plasma, clotting uses it all up.
Factors VII- Stable factor :-
This component is found in plasma and remains unaltered during the clotting process. It is resistant to heat and can tolerate temperatures as high as 56°C. It is still connected to prothrombin and is a protein. It is activated by extract produced from injured tissue, which speeds up the creation of extrinsic or tissue thromboplastin. When dicoumarin is administered and there is a vitamin K shortage, its creation is slowed down. Proconvertin is converted to convertin during blood coagulation.
Factors VIII- Antihaemophilic factor A :-
It has a molecular weight of over 200,000 and is dependent on barium sulfate. This component supports the production of endogenous prothrombin and endogenous thromboplastin. It is present in plasma and disappears when blood clots. It is protein in nature and is closely related to fibrinogen. It is an antihemophilic factor. Deficiency of this factor, which contributes to the destruction of platelets and the release of platelet component I (also called thromboplastin factor), causes hemophilia (a bleeding disorder). AHG deficiency causes classical hemophilia in males and is an inherited X-linked recessive trait. With a defective gene, the body is unable to produce globulins because it lacks a specific enzyme required for this important globulin synthesis.
Factors IX - Antihaemophilic factor B ( plasma thromboplastin factor or Christmas factor ) :-
Aluminum hydroxide absorbs it and, although heat labile, is relatively stable during storage. Ammonium sulfate accounts for 59% of precipitation. This component is required for the production of endogenous thromboplastin. Deficiency of this component causes hemophilia C, a sex-linked recessive inherited form of hemophilia in males. The name of the Christmas element comes from the first patient diagnosed with this type of disease. This component is not consumed by coagulation.
Factors X - Stuart prower factor :-
Chemically, it has some similarities to factor VII. Its synthesis is also delayed after administration of dicoumarin. Lack of this component leads to a moderate bleeding diathesis. In serum, it is rapidly degraded at 56 °C, but is stable at room temperature.
Factors XI - Plasma thramboplastin antecedent :-
This is eventually responsible for the synthesis of thrombin and is triggered by active Hageman factor. A sex-linked dominant, deficiency in this results in minor bleeding tendencies of the hemophilioid D type in both sexes.
Factors XII - Hageman factor :-
In biological terms, this is protein. Surface contact activates the inactive form. Consequently, this triggers the production of the plasma kinins by the proteinsplitting enzyme it. Increased vascular permeability and blood vessel dilatation are the outcomes.
Factors XIII - Fibrin stablising factor :-
The loose fibrin clot is converted into a solid fibrous clot by activation and Ca++. Furthermore, the solubility of the clot in urea solution is reduced by its activity. Individuals with congenital LLF malformations have difficulty in wound healing.