Staphylocoagulase as a hemostatic agent.

Staphylocoagulase, a protein produced by Staphylococcus aureus reactc with a plasma protein designated the Coagulase Reacting Factor (CRF) which is either prothrombin or is presumed to represent some active component of the prothrombin molecule."' The interaction of these two substances leads to the conversion of fibrinogen to fibrin, a reaction that proceeds in it*ro in the absence of calcium and in the presence of antico-agulants such as heparin and dicoumarol. The administration of large intravenous doses of coagulase to rabbits may result in in tivo defibrino-genation, sequestration of fibrin in tissues such as the lungs, and even in acute death.`8 The question has remained open, however, whether appropriate lower doses of coagulase may function as systemic hemostatic agents. It is well established, as in studies of coagulase antigenicity, that some levels of coagulase are very well tolerated by experimental animals, without evidence of any untoward effects. The present observations were therefore undertaken principally to determine whether systemically administered coagulase may shorten the whole blood clotting time of the experimental animal, such as the rat, and whether indeed any significant reduction in blood loss and in the duration of bleeding may be achieved. MATERIALS AND METHODS Staphylocoagulase was prepared by Drummond from S. aureus #104 according to a previously described method.' This preparation contained 0.31 mg. of protein per mg. of dry weight. The activity was such that when equal volumes of coagulase and non-inhibitory human plasma were incubated for 18 hours, 0.0001 mg. of coagulase in 0.5 ml. of peptone-saline produced a firm, invertable clot. CRF titrations consisted in making a series of doubling dilutions of cell-free plasma , generally in the range of 1:10 to 1:160. To 0.2 ml. of plasma dilution, in M/15 phosphate buffer at pH 6.85, 0.2 ml. of bovine fibrinogen (Armour) at a concentra