Pall leukotrap affinity prion-reduction filter removes exogenous infectious prions and endogenous infectivity from red cell concentrates

Background and Objectives Three recent probable cases of transmission of a variant of human Creutzfeldt-Jakob disease (vCJD) through blood transfusion suggest that the disease can be transmitted through transfusion of blood components from presymptomatic blood donors. In this study, we investigated the performance of a new filter for reducing the levels of infectious prions (PrPSc) from red cell concentrates (RCC). Materials and Methods Endogenous Infectivity: A pool of 500 ml of whole blood was collected from 263K-strain scrapie-infected hamsters into an anticoagulant, processed into non-leucoreduced RCC (NL-RCC), and then passed through a prion-reduction filter. Pre- and postfiltration samples were tested for PrPSc by Western blot and infectivity by inoculation of healthy hamsters. Results of the endogenous infectivity study after 200 days post-inoculation are discussed. Exogenous (Spiking) Study: Scrapie-infected hamster brain homogenates containing PrPSc were added to human RCC and then filtered. Levels of PrPSc were determined by Western blot assay. The effect of prior leucodepletion of 'spiked' RCC on PrPSc removal by the prion-removal filter was also assessed. Results In the endogenous infectivity study, at 200-day observation time, the prefiltered RCC transmitted disease to six of the 187 hamsters, whereas the filtered RCC did not transmit disease to any of 413 animals, P = 0.001. The prion filter also significantly reduced the concentration of leucocytes in the RCC by about 4 logs, P < 0.05. In the exogenous (spiking) study, the level of PrPres was significantly reduced in RCC P < 0.05. Prior leucodepletion of the RCC with a leucoreduction filter did not significantly reduce the concentration of exogenously spiked PrPSc, P > 0.05. Conclusion The use of this new prion-reduction filter should reduce the risk of vCJD transmission through transfusion of RCC, the most widely transfused blood component.