Existence and significance of a physiological anticoagulating system.

Abstract

WHEN moderate doses of tissue thromboplastin are injected into the jugular vein of rats the circulating blood loses its clotting properties, with the result that no intravascular thrombi are, as a rule, produced. This effect of thromboplastin depends upon its capacity for inducing the formation of thrombin in blood from the plasma prothrombin. In most cases intravenous administration of moderate doses of thrombin to healthy animals does not cause thrombosis, for the clotting mechanism becomes disordered almost immediately after the injections. At the same time the thromboplastic activity of blood shows a sharp decrease, while fibrinogen capable of reacting with thrombin disappears and heparin-like substances appear in the blood. This protective reaction, maintaining the blood in a fluid state in the vascular bed when thrombin arises in it, is brought about by the physiological anticoagulating system. Experiments have shown that in narcotic sleep resulting from inhalation of sulphuric ether, as well as from anæsthesia produced by an intramuscular injection of novocaine on both sides of the spinal column, this anticoagulating system ceases to function. It is this effect that accounts for the fact that coagulation of circulating blood and death from thrombosis have been found to occur in anæsthetized test animals (as opposed to controls in a normal physiological condition) after an intravenous administration of certain doses of thrombin (Table 1).