Plasma protein therapies: current and future perspectives

Although early developments in immunology and haemostasis indicated the potential therapeutic application of plasma fractions, it was not until Cohn's development of a stable plasma protein solution for the treatment of battlefield injuries in the Second World War that the manufacture of plasma derivatives became part of industrial pharmaceutics. The resulting albumin product remained the mainstay of the plasma fractionation industry for the next 40 years but the sequential removal of 'unwanted' fractions en route to the final albumin product lent itself to the characterization and use of other products. By the 1970s, the harvesting of cryoprecipitate before the initiation of the Cohn fractionation scheme allowed access to products for treating the haemophilias, using simple precipitation and, from the 1970s, chromatographic methods to concentrate the coagulation factors. Further minor modifications allowed the administration of the immunoglobulin in high intravenous dosages, significantly extending the usage and indications of immunoglobulin products. By the 1980s, the needs for haemophilia A had made factor VIII, rather than albumin, the driver for plasma fractionation, and the advent of recombinant coagulation factors in the 1990s contributed to immunoglobulin assuming the position of the plasma procurement driver. In recent years, the plasma industry has developed a relatively large range of products but has also entered a period of consolidation as various pressures, such as technological innovations, infectious and other risks and quality requirements-all of which are discussed in this review-decreased the demand of at least two of the three products that underpin the industry's current financial basis. At the same time, modern principles of evidence-based therapeutics are coming into play in the traditionally empirical base for most of the usage for plasma derivatives. The future use of plasma derivatives, at least in the developed world, will probably follow a different path to the one seen so far, and a sound understanding for the pathophysiology of the medical indications for plasma therapies should contribute to a continuing role for these medicines in modern therapeutics.