Xci. the Fluidity and Coagulation of the Blood

ONE of the landmarks in the history of the coagulation of the blood is the observation of Fredericq [1878] that heat coagulation occurs when the blood in the excised jugular of a horse is heated to 55-57°, after the subsidence of the' corpuscles. As the fibrinogens of the laboratory prepared by the method of Hammarsten [1879] and of'Schmidt [1892] coagulate at 560, it is commonly believed that they are identical with the precursor of fibrin in the blood. This was not however accepted as conclusive by two prominent physiologists, Wooldridge [1885, 1893] and Michael Foster [1888], each pointing out that fibrin ferment (thrombin) could be injected into the circulation in massive amounts without causing thrombosis, while similar quantities added to solutions of the fibrinogens of the laboratory provoke clotting. An attempted explanation of this anomaly, in the terms of Howell's [1911] views on coagulation, was advanced by Gasser [1917], who suggested that thrombin, when intravenously injected, combines with antithrombin to form an inactive substance termed metathrombin, it being assumed, without any direct evidence, that the introduction of thrombin into the circulation causes the liver to secrete an excess of antithrombin. But Pickering and Hewitt [1922, 2] have shown that massive doses of thrombin can be injected into the circulation of animals deprived of hepatic activity without causing intravascular clotting and these authors have deduced evidence that antithrombins are post-mortem products. Thus the lack of coagulant action of massive doses of thrombin in circulating blood is at least suggestive of some essential difference in the condition or composition of the fibrinogens of the laboratory and the precursor of fibrin in the living blood. The salts employed in the preparation of fibrinogen by Hammarsten's method cannot be regarded as without influence on the structure or condition of the latter material, as Howell [1914, 1] has found it is not possible by this method to obtain solutions of fibrinogen of uniform properties, part of the