12 Genetically engineered and affinity purified plasma proteins

Abstract

Blood transfusion to correct a plasma protein deficit began as long ago as 1840 with a report of the infusion of whole, fresh, uncrossmatched blood to a haemophilic boy (Lane, 1840) which stopped him from bleeding to death. Doubtless due to problems of incompatibility, this was not seriously followed up until the late 1920s (Payne and Steen, 1929), when it was reported that intravenous infusion of citrated human plasma, which had been stored frozen for 5 days, corrected the clotting time and caused bleeding to cease in a haemophilic boy. Large scale plasma separation to derive therapeutic infusable protein fractions was developed during World War II by Cohn and colleagues (1946). The Cohn fractions included a fibrinogen concentrate (fraction I), albumin (fraction V), immunoglobulins (fraction II) and aand [3-globulins (fractions IV and III). There were, however, no specific coagulation factor fractions; this is not surprising since at the time of development (1940-1945) no assays were available for coagulation factors other than fibrinogen and prothrombin. Minot and Taylor (1947) showed that Cohn's fraction I also contained what they called antihaemophilic globulin (i.e. it shortened the clotting time of haemophilic blood) but that its potency was highly variable. This study antedated the discovery that haemophilia was of two types, A and B, due to factor VIII and IX deficiencies respectively. In the 1950s, MacFarlane and co-workers (1954) developed some concentrates of factor VIII (measured using a specific assay) from bovine and porcine blood. Although highly valuable as the first true factor VIII concentrates, these preparations were limited in clinical use by severe side-effects due to animal proteins eliciting allergy and the aggregatory effect of animal von Willebrand factor (vWF) on human platelets. Various concentrates of factor VIII were produced during the 1950s and early 1960s but the first to gain wide popularity because of its simplicity and reliability was Judith Pool's cryoprecipitate (Pool et al, 1965). During the 1960s and 1970s further steps were introduced into factor VIII purification relying largely on the differential precipitation according to molecular weight.