Risk of variant Creuzfeldt–Jakob disease from factor concentrates: current perspectives

The demonstration of iatrogenic transmission of Creuzfeldt-Jakob disease (CJD) through therapeutic interventions led to substantial concerns in communities requiring blood products in the 1980s and 1990s. These concerns led some regulatory authorities to adopt a very precautionary approach and require recall of plasma products, including factor concentrates, which included donors at risk of CJD. The FDA's approach on recall contributed to a substantial lack of plasma products on the world market in the mid- to late 1990s. Growing epidemiological evidence of non-transmission of CJD to humans through blood, as well as demonstration of the plasma fractionation system's ability to eliminate CJD-type agents, led the FDA to rescind its measures for product recall in 1998. Although no evidence exists that the variant strain of CJD (vCJD) will behave any differently to the classic strain (cCJD) of the disease during fractionation, indications that higher levels of the strain may be present in the blood in vCJD, as well as the uncertainty regarding the epidemiology of the disease, has led to a new round of precautionary measures aimed at minimizing vCJD risk. Currently, the traditional approach to product safety through appropriate donor selection, screening using laboratory tests and systematic pathogen elimination is not completely possible for addressing the risk of vCJD. The only definite risk factor for vCJD is residence in a country where meat products from cattle with bovine spongiform encephalopathy (BSE) have been consumed; currently this is predominantly the United Kingdom but the appearance of BSE in other European countries has stimulated non-European regulatory authorities to defer blood donors from most of Europe. There is currently no screening test available for vCJD. Plasma fractionation techniques fortuitously appear to eliminate substantial amounts of vCJD like agents but only one pathogen eliminating technique, nanofiltration, has been proposed for specifically eliminating vCJD-like agents. Despite the current uncertainty, it is possible to be cautiously optimistic regarding the safety of factor concentrates from the risk of vCJD. An accumulating body of evidence suggests that it is unlikely that the plasma pool from countries with moderate BSE epidemics will contain sufficient levels of vCJD agent to lead to an infective final product. Nevertheless, the development of a blood screening test and more dedicated elimination methods are high priorities for the blood industry as it faces this new threat. The community of blood product users, including people with haemophilia, need to be in a position to make an informed choice regarding the risk of this new agent. Such a choice needs to take into account the alternatives to plasma product therapy such as recombinant concentrates and the risks to product supply ensuing from an excessive reliance on one form of product.