Protein products prepared from pooled human plasma are an essential class of therapeutics used mostly to control bleeding and/or immunological disorders. Because of the human origin of the starting material, there is a risk that these products may possibly transmit prions causing variant Creutzfeldt-Jakob disease (vCJD). No case of transmission of prions by plasma products has been observed. Case-by-case measures implemented in various countries, and several technical factors may contribute, to various degrees, to the prevention of the risk of transmission of prions by plasma products. Those measures include (a) the epidemiological surveillance of population in countries with cases of vCJD and/or bovine spongiform encephalopathies (BSE), (b) the deferral of blood donors who traveled or resided, for specific periods of time, to countries with BSE, or who received transfusion or tissue transplant, (c) the removal of leucocytes in plasma used for fractionation, and, last but not least, (d) the removal of the prion agents during the complex industrial fractionation process used to prepare plasma products. Numerous experimental infectivity studies, involving the spiking of brain-derived infectious materials, have demonstrated that several fractionation steps, in particular ethanol fractionation, depth filtration, and chromatography, can remove several logs of prions. Removal is explained by the distinct hydrophobic and aggregative properties of the prion proteins. In addition, nanofiltration using multi-layer membranes of 75 nm or smaller, which is commonly used for removing viruses from coagulation factors and immunoglobulins products, can remove more than 3-5 logs of spiked prions, presumably by size-exclusion and trapping mechanisms. Therefore, the risk of transmission of vCJD by human plasma products appears remote, but caution should prevail since the biochemical nature of the infectious agent in human blood is still unknown.
- Plasma products
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