Safety of coagulation factor concentrates.

Many of the adverse effects of the early crude plasma-derived concentrates were ameliorated by increasing their purity. Ironically, this strategy may have increased the risks of inhibitor formation and pathogen transmission due to the addition of processing steps which can alter the immunogenicity of clotting factors and the use of very large plasma pools, as dictated by economic considerations. In the absence of extremely sensitive donor screening, these large pools have a high probability of contamination with pathogens, which may be only partially offset by their removal during protein purification. One approach to minimize the risk of viral transmission is to use recombinant clotting factors produced without the use of human or animal plasma proteins at any step in the manufacturing or formulation process. However, as these proteins are synthesized in mammalian cells, even they pose a theoretical risk of pathogen transmission. For plasma-derived concentrates, the initial viral burden is minimized by screening individual donations and plasma pools with tests which detect virus-specific antibodies, protein antigens, or nucleic acid. These techniques are supplemented by non-specific viral reduction steps based on physical partitioning and/or inactivation of pathogens which share chemical or physical characteristics. Prion proteins, the putative causative agents of transmissible spongiform encephalopathies, do not share these characteristics with viruses, and it remains to be determined whether they partition into clotting factor concentrates and whether the current strategies can efficiently remove or inactivate them. For all blood-borne pathogens, active immunization (currently available only for hepatitis B and A) and continued surveillance of susceptible recipients are critical approaches to achieving optimal safety of coagulation factor concentrates.