Studies on the Coagulase-reacting Factor

Among the diverse views which have been advanced to explain the mechanism of the clotting of blood by staphylocoagulase, it has been suggested that coagulase acts directly on fibrinogen,4"3 or that it is a proteolytic enzyme,3 similar to trypsin, which activates prothrombin. Recently, however, the enzymic nature ofcoagulase has been questioned.12 Smith and Hale,' in a significant contribution, brought forth evidence that an "activator" is present in plasma, and suggested that coagulase itself is a prothrombin-like substance which reacts with the specific activator to form a thrombin-like product which, in turn, reacts with fibrinogen. In a subsequent study,10 however, they proposed an alternative hypothesis, namely, that coagulase is the activator or kinase, while the substance in plasma, previously called "activator," might be prothrombin-like in nature.t The critical experiment which led Smith and Hale' to conclude that coagulase does not act directly on fibrinogen depended on the procedure of precipitating dilute plasma at a pH of 5.3, as developed by Mellanby' for the purification of prothrombin. In the hands of the British investigators, this procedure led to a dissociation of fibrinogen from the plasma factor, since such preparations, containing fibrinogen, lacked the coagulase-reacting factor. The Mellanby precipitate contains most of the components of plasma which partake in the coagulation of blood, and it therefore appeared of particular interest that C.R.F. was not demonstrable in such a preparation. It raised the problem of attempting to determine the plasma components which possess this activity. As the first step, therefore, in defining more completely the coagulase-plasma interaction, studies were undertaken to identify the plasma fractions which react with coagulase.