Biochemical techniques of isolation and purification, immunological methods of identification have shown that blood clotting has the character of a “chain reaction” in which apart from the four factors constituting the basis of the classic theory (factor I—fibrinogen ; factor II—prothrombin ; factor III—thromboplastin ; and factor IV- calcium), a number of other factors are also involved.
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We will first consider these factors and then we will discuss the mechanism of blood clotting.
Factor I (fibrinogen):
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Virchow (1845) first of all pointed out that fibrinogen is a plasma protein of high molecular weight (400,000- 500,000) which actively takes part in the clotting of blood. Fibrin is the end product of the blood clotting reaction.
Latest discoveries show that fibrinogen in its native state consists of particles of mycella which unite at the time of clotting to form fibrin threads of about 0’4/x long. Most fibrinogen is synthesized in the liver.
The biological feature of fibrinogen, is that it clots and the clotting occurs in the presence of a specific enzyme, thrombin.
Factor II (prothrombin):
This factor was discovered by Schmidt in 1863. Prothrombin is a glycoprotein synthesized in the liver. Vitamin K is essential for its formation.
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Inactive prothrombin is converted into active thrombin in the presence of thromboplastin and accelerators and calcium ions.
The amount of thrombin formed is proportional to the initial level of prothrombin. However, its insufficient amount is always present in the circulating flood in connection with continuous latent microcoagulation.
Prothrombin has the molecula weight about 69,000, while that of thrombin sapproximately hal that o£ prothrombin, i.e., about 33,000.
Factor III (thromboplastin):
It is a lipoprotein found in blood platelets and tissue cells. Its role was discovered and studied by Schmidt.
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It is secreted in its inactive form called prothromboplastin (Kudryashov, 1948) in the tissues.
Under the action of a powerful activator, proconvertin contained in the plasma tissue, prothromboplastin is transformed into active thromboplastin.
Modern investigators regard the action of thromboplastin as enzymatic, catalyzing the process of conversion of prothrombin into thrombin in the presence of factors V, VII and X, Ca++ and phospholipids.
Factor IV (calcium ions):
Although the role of calcium ions has not been definitely established, its importance in the process of haemostasis is generally recognized.
It is not directly involved in the reaction of thrombin formation but it is required for the formation of prothrombin activator, and for the formation of insoluble fibrin clot.
Factor V (labile factor):
This factor was first of all described by Owren in 1947 and is essential for conversion of prothrombin to thrombin by tissue extract and plasma factors. Factor V is absent from serum being consumed during blood clotting.
Factor VII (stablefactor, autoprothrcmbin I):
This factor is required for the formation of prothrombin /activator by tissue extract and is present in serum as well as plasma as being not consumed during blood clotting.
Its deficiency is rarely occurred but is frequently induced by oral anticoagulated drugs of the coumarin type.
Factor VIII (antihaemophilic globulin, antihaemophilic factor):
This factor is required for the formation of prothrombin activator from blood constituents and is found absent from blood serum being consumed during blood clotting. The deficiency of this factor may cause haemophilia.
Factor IX (Christmas factor, plasma thromboplastin component, autoprothrombin II):
This factor is also required for the formation of prothrombin activator from blood constituents.
It is found in plasma and it is activated during clotting so that the activity in serum is much greater than in plasma.
The deficiency of this factor is associated with a congenital haemorrnagic state resembling haemophilia (Christmas disease).
Factor X (Stuart-power factor):
This factor is found in plasma and serum and is responsible for haemorrhagic state is deficiency.
Factor XI (plasma thromboplastin antecedent):
This factor is found in plasma and serum and is required for formation of prothrombin activator from blood constituents. Its deficiency causes a haemorrhagic state.
Factor XII (Hageman factor):
This factor is also found in plasma and serum and is required for the formation prothrombin activator from blood constituents. In the deficiency of this factor blood clots very slowly.
Factor XIII (fibrin stabilizing factor):
This is a plasma protein which causes polymerization of soluble fibrin to produce insoluble fibrin. Its deficiency causes haemorrhagic state.
Blood platelets are not true cells but cell fragments formed in the bone marrow, lungs, liver and spleen.
These tend to clump readily, cling to rough surfaces and liberate phospholipids which are essential for clotting in the absence of tissue extract.