CHEMICAL, CLINICAL AND IMMUNOLOGICAL STUDIES ON THE PRODUCTS OF HUMAN PLASMA FRACTIONATION. XXXIII. THE COAGULATION DEFECT IN HEMOPHILIA: THE EFFECT IN VITRO AND IN VIVO ON THE COAGULATION TIME IN HEMOPHILIA OF A PROTHROMBIN AND FIBRINOGEN-FREE NORMAL PLASMA AND ITS DERIVED PROTEIN FRACTIONS 123

Patek and Taylor (1) in 1937 demonstrated that the activity of normal plasma in shortening the coagulation time of hemophilic blood could be found almost quantitatively in a derived globulin fraction.In 1939, Lozner, Kark and Taylor (2) showed that Berkefelded normal plasma free from fibrinogen and prothrombin had hemophilic clot- promoting power similar to that of untreated nor- mal plasma.In unpublished investigations (3), they found that a globulin fraction derived from this fibrinogen and prothrombin-free plasma also had antihemophilic activity.Pavlovsky and Si- monetti (4) in 1944, using the technique of Patek and Taylor, demonstrated that globulin substance prepared from the plasma of a patient with con- genital fibrinogenopenia had normal antihemo- philic activity.Investigation in this laboratory of plasma pro- tein fractions prepared by the Harvard Physical Chemistry Department showed marked in vitro (5) antihemophilic activity to be present in Frac- tions I and II + III.Fraction I studied in vivo (6) likewise showed marked power to shorten the coagulation time of hemophilic patient's blood.This investigation was undertaken to study the 1 This is paper No. 45 in the "Studies of Plasma Pro- teins" of the Harvard Medical School, on products de- veloped by the Department of Physical Chemistry, from blood collected by the American Red Cross.2 The expenses of this investigation were defrayed in part by gift from the Smith, Kline and French Labora- tories, Philadelphia, and in part by a grant "In recognition of Dr. Francis W. Peabody's services to the Foundation" by the Ella Sachs Plotz Foundation.