A preclinical screening test for modified hemoglobin to bridge the gap between animal safety studies and use in human

The infusion of large amount of modified hemoglobin as blood substitute can potentially result in hypersensitivity and anaphylactic reactions, antibody-antigen reactions and others. Animal safety studies are important. However, response in animals may not be the same as in human. Before injecting into human, we may need to use an in-vitro screening procedure. One approach is based on testing the effects of modified Hb on complement activation (C3a) of human plasma. This paper describes this screening test. It also discusses how this may potentially be used. For instance using this to test for contamination from trace membrane fragments with blood group antigen or lipids, antibody-antigen complexes, endotoxin, trace fragments of microorganisms, residual amounts of some polymers, emulsifying agents, and organic solvents. There is also the possibility of obtaining plasma from a very large human population and analyse each of these to study the epidemiology of adverse reactions in different groups and types of patients.