THE COAGULATION DEFECT IN HEMOPHILIA. THE EFFECT IN HEMOPHILIA OF INTRAMUSCULAR ADMINISTRATION. OF A GLOBULIN SUBSTANCE DERIVED FROM NORMAL HUMAN PLASMA 1

Abstract

The recent investigations of Patek and Stet- son (1) 2 indicate that the defect in coagulation of blood in hemophilia resides in the plasma rather than in the platelets. Patek and Taylor (2, 3) 2 isolated a substance from citrated normal cellularfree plasma, by isoelectric precipitation, with which was associated the clot-promoting factor of normal plasma. This substance was effective, both in vitro and after intravenous injection, in reducing the coagulation time of hemophilic blood. By the same method, a similar substance in approximately the same quantity was obtained from citrated hemophilic plasma, but its clot- accelerating power on hemophilic blood was much less marked. In the absence of definite knowledge concerning the nature of the effective mate- rial it was called "globulin substance " which is the nomenclature that will be retained in this communication. The material was thermolabile, insoluble in water, partially soluble in physiological saline solution, and non-diffusible. It was precipitated in optimal amounts between pH 5.9 and 6.4. The material passed readily through a Berkefeld filter without loss of potency and was almost completely inactivated by small excesses of alkali (3). Bendien and Creveld (4) have iso- lated a substance, by dilution and acidification, from normal serum which they injected intra- muscularly and intravenously and report favor- able results.