Recent evolution of clotting factor concentrates for hemophilia A and B. Transfusion Practices Committee

EFFORTS TO MAKE concentrates of factor VIII (FVIII) (for persons with hemophilia A) and of factor IX (F IX: as F IX complex, also known as prothrombin complex, for persons with hemophilia B) began in the 1950s and progressed during the 1960s.’~~ By the early 1970s, freezedried concentrates of FVIII and of F IX complex made by pharmaceutical companies from pooled plasma became widely available in the United States. The custom of repeated plasmapheresis of paid normal donors allowed the United States to produce concentrates in abundance for domestic use and to become the world’s major exporter not only of concentrates but also of plasma for fractionation abroad. In the 1960s, cryoprecipitate (a frozen, single-donor source of FVIII, von Willebrand factor, and fibrinogen) was developed for production by local blood banks, predominantly for local use. The low incidence and generally mild nature of allergic reactions to cryoprecipitate and, especially, to concentrate made home self-infusion a practical and popular option for hemophiliacs, freeing them from frequent trips to clinics and emergency rooms and allowing much more rapid treatment of hemorrhages. The convenient stability of lyophilized products at ambient or refrigerator temperatures plus the ease of reconstitution and administration led to a preference for concentrate over cryoprecipitate for the management of hemophilia A in most areas of the country. During the 1970s, improvements in clotting factor concentrates were directed largely toward such goals as reducing allergic and other recipient reactions and improving solubility, yield (units of clotting factor recovered from plasma), and, to a limited extent, specific activity (units of clotting factodmg p r ~ t e i n ) . ~ . ~ Usually, such changes were incremental, requiring only amendments to licenses, while brand names remained the same. New brand names entered the vocabulary when additional fractionators entered the concentrate market. During the 198Os, however, changes in concentrates were major and relatively frequent and were due, for the most part, to efforts to prevent the transmission of bloodborne viral infections. Brand names were modified, usually by suffixes designating the method of purification or of virus inactivation. At times, multiple versions of one brand were on the market simultaneously. Only a few coagulation linguists could interpret the Babel of nomenclature. Confounding the perplexity, additional methods for screening donors were introduced and mandated at different times during the same epoch. A given brand might be manufactured from plasma screened by certain means one year, and by additional means the next year, with no change in brand name. Furthermore, nearly all concentrates had an outdate period of 2 years, and thus, concentrates made from plasma collected according to the standards of prior years often were on the market at the same time as concentrates made from plasma collected according to current standards. This report describes the changes in concentrates used for the treatment of hemophilia A and B during the 1980s, the rationale for those changes, the nomenclature for the various concentrates, and the concentrates available today.