The Standardization of Blood Coagulants**Read before Scientific Section, A. Ph. A., New Pork meeting, 1919

Herbert C. Hamilton
1920 The Journal of the American Pharmaceutical Association (1912)  
Hemorrhage, whether due to an abnormal condition of the blood or to lacerated tissues intentional or otherwise, has long been the subject of careful consideration. Wiggers' found that in the different stages of pulmonary hemorrhage pituitary extracts, by their action in raising systemic arterial pressure, while at the same time lowering that in the pulmonary circuit, are peculiarly adapted to its control. This agent, however, has no direct effect on the rate of blood coagulation, its peculiar
more » ... fectiveness being due to its action on the heart and vessels. Adrenalin is frequently used and with very good results since it acts to constrict the vessels locally, retarding the flow of blood and permitting the formation of the clot. But so far as known, it has no action on the character of the blood to hasten coagulation. In hemorrhage, while any step which will favorably influence coagulation is t o be recommended, no procedure is equal to one which will shorten the coagulation time of the blood itself, promoting the formation of the clot at the exposed surface of the ruptured vessels and thus more quickly sealing them. The accepted theory of blood coagulation and its remaining fluid in the vascular system is that the substance essential to the formation of fibrin from fibrinogen is thrombin, which is held in the form of prothrombin by a hypothetical anti-thrombin or anti-prothrombin. Possibly both substances are present, the one to hold the prothrombin, the other to destroy or combine with any thrombin which may be formed. It is very difficult seriously to disturb the equilibrium which maintains intravascular fluidity. When the tissues are lacerated, however, the shed blood, if of normal character, will soon form a clot and tend to seal the wound. From the edges of the wound the tissue fluids exude, and from the blood platelets, which quickly disintegrate when exposed to the air, similar substances are set free. These two sets of fluids mix with the blood and start the process of coagulation which consists essentially in liberating the prothrombin from its antithrombin binding and in promoting the reaction first between prothrombin, thrombokinase and calcium ions by which thrombin is produced, then between the thrombin and fibrinogen, by which fibrin is split off and the clot formed. Morawitz2 designated this substance which initiates coagulation as thrombokinase. The change which has taken place appears to be two-fold. If we consider coagulation as an abnormal condition o€ the blood, the first departure from the normal is the cessation of metabolism by which the globulins are returned to the blood. When cytoglobulin,3 the anti-coagulative substance-anti-thrombin-is no longer poured into the blood, prothrombin is set free and predominates. With the calcium of the blood and in the presence of the tissue fluid containing thrombokinaae, which now appcars and constitutes the second abnormal condition, thrombin is produced and the clot-formation at once proceeds if the normal blood has been in proper equilibrium. Some have assumed that the office of the
doi:10.1002/jps.3080090204 fatcat:2ojvxrep2vhmrgyi7mnrlxwwjy