The Problem of the Lipoid Thromboplastins *

For a long time, it was accepted that calcium and cephalin activate prothrombin. There were secondary questions about the identity of the phosphatide and whether it was important that the phosphatide be bound to protein. Otherwise the issue was closed. Now the basic premise is in sufficient doubt to warrant a restatement of the problem in the light of newer observations. " . . . I have come upon a fact which is of the very highest importance not only for the question of the coagulation of the blood but for the very much greater question of the nature of the chemical processes in protoplasm, which constitute life. This fact is that lecithin, a body omnipresent in protoplasm, can bring about coagulation." So wrote Wooldridge, in 1883.' The material he thus caused to coagulate was specially treated plasma from dogs injected with peptone. The plasma of peptonized dogs was also used by Howell'0 to assay the coagulant activity of his cephalin preparations. At that time, Howell employed one of Nolf's terms and wrote of "thromboplastic substances" as "the extractible substance or substances in the tissues which facilitates the process of clotting." This is considerably more general than his previous description' of "thromboplastic substance or thromboplastin, which neutralizes the antithrombin... ." Then, and ever since, "thromboplastin" has been a rather broad and variable term. It is now applied to diverse materials from fixed tissue or blood which accelerate coagulation, especially those which accelerate production of thrombin.