Relation of contacting surface and anticephalin activity to the maintenance of the fluidity and coagulability of blood.

By LEANDRO M. TOCANTINS, M.D. T ENTATIVE explanations of the mechanism of coagulation of the blood must necessarily be concerned as well with the equally important problem of the maintenance of its fluidity in the circulation. Fluidity and coagulability are properties of the blood that are in a sense antagonistic to each other. To understand what promotes coagulation, one must also be familiar with the factors that discourage this change and thereby keepthe blood in a fluid state. Both physical states areessential in their proper places. Excessive bleeding may result when the blood is so stable that it remains liquid longer than it should after it leaves the vessels; if, on the other hand, the blood clots within the vessels, where it should not, an interruption of the circulation may follow. It is by preserving a balance between fluidityinducing (anticoagulant) and coagulation-promoting (coagulant) factors that the blood maintains itself as a circulating medium. Two theories of blood coagulation, with substantial experimental supportthose of Bordet’ and of Howell’-have attempted to account for the state of fluidity of circulating blood as well as for the development of coagulation in shed blood. Bordet divided the reactions involved into three phases: I. Proserozyme (inactive prothrombin) on contact with a suitable surface or with lipid cytozyme = serozyme (active prothrombin). 2.. Serozyme (active prothrombin) + cytozyme (lipid from platelets and tissue cells) in the presence of calcium = thrombin. 3. Thrombin + fibrinogen = fibrin. Howell also recognized the existence of three successive reactions: I . Prothrombin / antiprothrombin (heparin) + platelet or tissue factor (cephalin) = free prothrombin. 2,. Free prothrombin + calcium = thrombin. 3. Thrombin + fibrinogen = fibrin. With the exception of Pickering3 and Fuchs,4 most workers, especially in publications within the last ten years, do not mention the first phase and therefore leave unexplained the question of the maintenance of the fluidity of circulating blood. In common with Bordet, Howell recognized that the prothrombin in circulating blood differs from that in shed blood. According to Howell, the circulating prothrombin is bound with antiprothrombin (heparin) and is freed from the latter by the platelet or tissue factor that neutralizes the antiprothrombin. With this point Bordet could not bring himself to agree, and much of the evidence that he brought against it received further support from Pickering,3 Mellanby,5 and others. Bor-