The relation of certain fractions of the plasma globulins to the coagulation defect in hemophilia.

have indicated that normal cell-free human plasma contains some factors which are deficient in hemophilia. There is evidence that by the parenteral administration of derivatives of normal cell-free plasma in hemophilia, the coagulation defect can be modified toward normal. The present communication reviews some of the older work on this subject and presents new evidence accumulated during the past three years. One of the earliest studies on the use of fresh whole blood in the treatment of hemophilia was made by Minot and Lee in I9I6. They ascribed the beneficial effects of transfusion of whole blood to the platelets thus added to the patient’s circulating blood. In the same year, Addis8 showed that the administration of whole blood or of serum reduced the coagulation time of hemophilic blood. Patek and Stetson’ reinvestigated this problem in 1935 and found that small transfusions, as little as 30 cc., of fresh whole blood were as effective as large amounts in the initial reduction of the coagulation time in hemophilia, but that the reduction of the coagulation time was much more transient when these small amounts were used . These authors found that the beneficial effects of fresh whole blood could be duplicated by the use of fresh normal human plasma. They then deprived the plasma of its platelet content and found that the filtrates so obtained were equally effective in reducing the coagulation time of hemophilic blood in vivo. From the foregoing evidence it seemed reasonable to conclude that fresh normal whole blood or platelet-free plasma contained a material which was effective in shortening the coagulation time of hemophilic blood. Transfusions of hemophilic blood or of hemophilic plasma failed to have such a beneficial effect.9 In other words, there seemed to be evidence that hemophilic blood was deficient in some factor or factors present in normal blood. Competent investigators have shown that the coagulation defect in hemophilic blood could not be related to deficiency in calcium ion,’#{176}’ “ “ “ prothrom-