Coagulation of Blood

Coagulation of Blood


the transformation of liquid blood into an elastic clot; a protective reaction of man and animals that prevents the loss of blood. Coagulation occurs in a series of biochemical reactions involving a group of coagulation factors—plasma proteins and Ca2+ ions—that are designated by roman numerals. Factor I is fibrinogen, factor II prothrombin, factor III thromboplastin, factor IV calcium, and factors V and VI plasma and serum accelerator globulins, respectively. Factor VII is proconvertin, factor VIII antihemophilic globulin A, factor IX antihemophilic globulin B, or Christmas factor, and factor X Stuart-Prower factor, also called autoprothrombin C or thrombokinase. Factor XI is plasma thromboplastin antecedent, factor XII Hageman factor, and factor XIII fibrin stabilizing factor, or fibrinase.

Several components of the coagulation system are present in formed blood elements. For example, thrombocytes contain platelet factor 3 (thromboplastin antecedent), analogues of factors V and XIII, and fibrinogen. The principal reactions of blood coagulation occurring with the participation of enzymes are the formation of active thromboplastin, the conversion of prothrombin into thrombin, the conversion of fibrinogen into fibrin, and the stabilization of fibrin.

The enzymatic theory of blood coagulation was advanced by A. A. Shmidt, a professor at the University of Iur’ev (now Tartu), in studies published between 1872 and 1895. It was later discovered that coagulation is initiated by an internal process (thromboplastin is formed from plasma coagulation factors, and factor 3 from thrombocytes undergoing destruction), as well as an external one (thromboplastin is formed with the participation of a substance known as tissue fluid, released as a result of tissue injury). Several modern theories of blood coagulation, including the cascade hypothesis of the British scientist R. MacFarlane (1965–66), have been advanced on the basis of experimental and clinical findings. According to MacFarlane’s hypothesis, internal coagulation begins with activation of factor XII and its conversion to factor Xlla. Factor XII is activated when it comes in contact with a wettable surface, when it interacts with lipogranules (lipoprotein particles in the blood), when there is an excess of epinephrine in the bloodstream, and under other conditions. Factor Xlla initiates a series of sequential reactions involving factors XI to V inclusive, which are present in the blood plasma. The result is the formation of blood thromboplastin, or prothrombinase.

When a tissue antecedent penetrates the blood (extrinsic pathway of coagulation), active thromboplastin is formed with the participation of plasma factors V, VII, and X and of Ca2+ ions. Blood or tissue prothrombinase converts prothrombin (factor II) into the enzyme thrombin (factor IIa). This enzyme detaches the peptide fragments from fibrinogen, converting it into a fibrin monomer. Unstablized (soluble in urea and some acids) fibrin undergoes enzymatic stabilization by factor XIIIa in the presence of Ca2+ ions. The result is an insoluble fibrin polymer, which is the matrix of a blood clot, or thrombus. MacFarlane’s hypothesis is based on experimentation, but it does not take into account the role of natural anticoagulants present in the blood or the physiological regulation of the liquid state of blood and of the blood’s coagulation.

Blood coagulation time varies considerably from one species to another. Human blood extracted from the vascular bed normally clots in 5–12 min. A thromboelastograph is used to record coagulation time and impairment of coagulation. Coagulation is delayed in many diseases, often because of a deficiency, acquired or inherited, of one or more coagulation factors. For example, in cases where vitamin K cannot be absorbed, the ensuing hemorrhages result from impairment of the biosynthesis of factors II, VII, IX, and X. The same effect may arise from administration of excessive doses of indirect-action anticoagulants—antagonists of vitamin K—such as bishydroxycoumarin and its derivatives.

An example of a congenital impairment of coagulation is a deficiency of factor VIII (hemophilia A), which is transmitted by a female sex chromosome. A similar disease may be caused by an accumulation of factor VIII antagonists formed in the body or by impairment of the factor’s structure. Variants of hereditary deficiency or defects in molecular structure are known to occur in almost all the plasma coagulation factors.

Disturbances in the regulation of the blood’s liquid state and of coagulation also result in thrombogenesis, or the formation and stabilization of blood clots in the vascular bed. The formation of a thrombus cannot be ascribed solely to an intensification of coagulation. Such pathological conditions may also be caused by a local or systemic impairment in the function of the anticoagulation mechanism that regulates the liquid state of the blood. If the regulatory relationships between the coagulation and anticoagulation mechanisms are disrupted, a combination of hemorrhage and disseminated thrombosis may result.


Kudriashov, B. A. “Problema reguliatsii zhidkogo sostoianiia krovi i vzaimootnosheniia svertyvaiushchei, fibrinoliti cheskoi i protivosvertyvaiushchei sistemy.” Uspekhi fiziologicheskikh nauk, 1970, vol. 1, no. 4.
Kudriashov, B. A. Biologicheskie problemy reguliatsii zhidkogo sostoianiia krovi i ee svertyvaniia. Moscow, 1975.
Schmidt, A. Weitere Beiträge zur Blutlehre. Wiesbaden, 1895.
MacFarlane, R. G. “The Basis of the Cascade Hypothesis of Blood Clotting.” Thrombosis et diathesis haemorrhagica, 1966. vol. 15, no. 3/4.
Laki, K. “Our Ancient Heritage in Blood Clotting and Some of Its Consequences.” Annals of the New York Academy of Sciences, 1972, vol. 202.
Owren, P. A., and H. Stormorken. “The Mechanism of Blood Coagulation.” Reviews of Physiology, 1973, vol. 68.


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