A method of preparation for therapeutic use of a concentrate of factors IX, 11 and X and a separate concentrate of factor VII is described. The method is based upon adsorption of the factors on DEAE-cellulose from plasma or from the supernatant after removal of factor WI. Conditions of elution are selected so that, in a single step, the factors are obtained at a suitable salt concentration and potency to permit injection of a therapeutic dose by syringe. The yield of factor IX in vitro is about 5~7 5 % and the purification about 300-fold. The yield of factor VII is lower and variable. Experience in the use of 14 batches of factor-IX concentrate in the treatment of 29 patients and on the use of a batch of factor-VII concentrate in the treatment of one patient is described. The in viuo dose response to factor I X made by different methods is compared,The first reliable therapeutic concentrate of factor IX was prepared by a method requiring specially collected blood (Didisheim et al, 1959; Blatrix & Soulier, 1959). W e found that the residue from a large-scale fractionation of human plasma for factor VIII, 7-globulin and albumin, contained sufficient factor I X to make it an acceptable starting material (Biggs et al, 1961). The method in current use, which will subsequently be called the 'routine' method, was described by Bidwell et al(x967, 1972). The product (subsequently called the 'routine' material) is a white powder which dissolves readily giving a clear solution in which the factor-IX concentration is 4-10 x that of plasma and the purification 250-550 x . The overall yield by in vitro assay is c 20% of the factor IX assumed to be present in the original starting plasma, DEAE-celldose was used by Melin and co-workers (Tdlis et a!, 1965) for preparing a factor-IX-prothrombin compIex from plasma separated from blood decalcified by ion-exchange resin. Deggeller (1969) and Casillas et al (1969) showed that the same principle could be applied to ACD plasma from which factor VIII for therapeutic use had previously been separated. Both methods have practical disadvantages (see Table I).The establishment of the Plasma Fractionation Laboratory as part of the Oxford Haemophilia Centre presented an opportunity to deveIop a method of producing factor-IX concentrate from a starting material other than a large-scale fractionation residue. The criteria adopted for a method intended to supersede our present well-established procedure were : Correspondence: Mr G. W. R. Dike, Oxford Haemophilia Centre, Churchill Hospital, Oxford. G TABLE 11. Yield, purification and patients' responses for 14 batches of factor-IX concentrate Batch
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.