The history of plasma fractionation began with the need to develop blood serum products to help soldiers suffering from shock and burns in the Second World War. Dr. Edwin Cohn, of Harvard University, was a key figure in the development of a process to separate proteins from human plasma. The “Cohn fractionation process,” still forms the basis of most modern plasma fractionation facilities, bears his name.
Originally, the aim was to separate albumin, which represents 55-60% of the total protein volume in plasma, for use in injured soldiers. Over time, additional proteins were separated and used clinically. The Cohn fractionation process originally developed in the 1940’s involves modifying the pH, ethanol concentration and temperature to separate proteins through precipitation into five “fractions” (I-V). The first fraction is “cryoprecipitate” which contains “factor VIII,” “factor IX” and other heavy proteins, the first two of which are used in hemophilia treatment. Before plasma fractionation and purification, hemophilia patients had to use cryoprecipitate to control bleeding. In the 1960’s, methods were developed to purify factor VIII and later factor IX from fraction I of plasma, and hemophilia patients were able to use these purified products for treatment over time. In the 1950’s intramuscular immunoglobulin (IMIG) was developed from fractions II and III and introduced as replacement therapy for patients with congenital antibody deficiencies.
Since the intramuscular injections were painful, only small volumes could be administered, which did not allow for adequate dosing. In the 1980’s, purification methods had sufficiently improved to enable the production of “intact” molecules (similar to those found in human plasma) with full biological efficacy, allowing the development of commercial preparations of intravenous immunoglobulin (IVIG). In the 1980’s, alpha-1 protease inhibitor (A1PI) was purified from fraction IV and marketed for a congenital form of emphysema caused by low alpha-1 protein levels. Fraction IV also comprises antithrombin III, while fraction V mainly contains albumin.
In the 1970’s, at the plasma fractionation plant of the Swiss Red Cross Blood Transfusion Service in Bern, Switzerland, Kistler and Nitschmann improved the fractionation process to generate higher yields in the production of some proteins. The next improvement was the development of chromatography processes to purify specific proteins, such as immunoglobulins, which further increased production yields. Research in improving the fractionation of plasma is continually ongoing as companies and researchers develop new ways of maximizing the yield of each protein from human plasma.
Today, modern plasma fractionation plants are large and complex, capable of fractionating millions of liters of plasma into a wide variety of therapeutic products.