A study of the normal blood coagulation process reveals a two-stage reaction in which four main concepts about the chemistry of blood coagulation are integrated in proper order. The first stage of the reaction, in which the prothrombin of plasma is activated to thrombin represents a co-ordination of the first two concepts, viz., (1) prothrombin activation and (2) inhibition of prothrombin activation. The second stage of the reaction in which thrombin interacts with plasma fibrinogen to form fibrin, represent an integration of the last two concepts, viz., (3) action of thrombin and (4) neutralization of thrombin activity. In prothrombin activation, substances which are essential in the conversion of prothrombin to thrombin, are calcium-irons and active thromboplastin as present in tissue extracts. There are certain other substances, which either accelerate the process, or are otherwise important in the initiation of it.
Coagulation of blood are is a complicated process in which more or less thirteen coagulation factors are involved. The appended table shows the factors authenticated by the International Nomenclature Committee and designated by Roman numerals.
The International Roman Nomenclature for Blood Coagulation Factors.
Factor Synonym
I - Fibrinogen
II - Prothrombin
III - Thromboplastin(tissue extract)
IV - Calcium
V - Proaccelerin, liable factor.
VI - Accelerin (now obsolete)
VII - Proconvertin
VIII - Antihaemophilic factor (AHF)
IX - Christmas factor, plasma thromboplastin
Component(PTC)
X - Stuart-Power factor
XI - Plasma thromboplastin antecedent
(PTA)
XII - Hageman Factor
XIII - Fibrin stabilising factor
A scheme illustrating the way in which these factors interact to produce coagulation of blood in a glass tube is shown below, which illustrates “intrinsic thromboplastin” formation.
In the inhibition of prothrombin activation, two substances are important; these are (1) Antithromboplastin, – a lipid, normally present in plasma and (2) Heparin, – which, acting with a plasmaprotien co-factor, inhibits the activation of prothrombin. In the action of thrombin, the modern concept is that once thrombin is formed it interacts with the fibrinogen of plasma, so that, in the very beginning of this interaction thrombin removes a small peptide from the fibrinogen molecule after which the latter of neutralization of thrombin activity centres round mechanism of antithrombin phenomena in which four main events are concerned, viz., (a) a small amount of thrombin is absorbed on the fibrin it self; (b) a plasma protein slowly neutralizes thrombin activity (c) heparin, with a plasma co-factor, interferes quickly with the interaction of thrombin and fibrinogen and (d) certain interactions arising during the activation of prothrombin cause neutralization of thrombin activity. Delayed coagulation in vitro occurs when the calcium is less than 2’5mg. per cent. or less, but such a calcium level in blood is incompatible with life. Hence, calcium deficiency of tissue thromboplastin does not ever exist as a cause of any coagulation defect. Hence, defective coagulation may only, either (A) when there are deficiencies of one or more of the following elements concerned in the normal coagulation reaction, viz. , (1) prothrombin (2) plasma and platelets factors which contribute towards prothrombin conversion and (3) fibrinogen, or (B) when the inhibitors predominate, eg., excess of antithromblastin or heparin or other anticoagulants. An aetiological classification of haemorrhagic disorders, in which the intravascular abnormality is defective coagulation of blood, can be made as follows :
A. Prothrombin defect
Congenital – Hypoprothrombinaemia ( or the so-called haemophilia neonatorum).
Acquired – Biliary obstruction, liver disease, fatty diarrhea, vitamin K deficiency or following the administration of drugs of dicoumarol group which mainly reduce Factor VIII.
B. Prothrombin accelerator defects : Lack of antihaemophilic globulin ( Factor (VIII), Factor V, Factor VIII, Factor IX (PTC), PTA(Plasma thromboplastin antecedent).
C.Prothrombin activation-inhibitor defect : Excess of antithromboplastin haemophilia.
D. Fibrinogen defects :
Congenital – Fibrinogenopenia.
Acquired – Severe liver damage, fibrinolysis.
E. Anticoagulants : (i) Anti-prothrombins – Dicoumarol, salicylates,
heparin
(ii) Anti-thrombins – Heparin, hirudin.
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