Impact of leucocyte depletion and prion reduction filters on TSE blood borne transmission

Abstract

The identification in the UK of 4 v-CJD infected patients thought to be due to the use of transfused Red Blood Cell units prepared from blood of donors incubating v-CJD raised major concerns in transfusion medicine. The demonstration of leucocyte associated infectivity using various animal models of TSE infection led to the implementation of systematic leuco-depletion (LD) of Red Blood cells concentrates (RBCs) in a number of countries. In the same models, plasma also demonstrated a significant level of infectivity which raised questions on the impact of LD on the v-CJD transmission risk. The recent development of filters combining LD and the capture of non-leucocyte associated prion infectivity meant a comparison of the benefits of LD alone versus LD/prion-reduction filters (LD/PR) on blood-borne TSE transmission could be made. Due to the similarity of blood/plasma volumes to human transfusion medicine an experimental TSE sheep model was used to characterize the abilities of whole blood, RBCs, plasma and buffy-coat to transmit the disease through the transfusion route. The impact of a standard RBCs LD filter and of two different RBCs LD/PR prototype filters on the disease transmission was then measured. Homologous recipients transfused with whole-blood, buffy-coat and RBCs developed the disease with 100% efficiency. Conversely, plasma, when intravenously administered resulted in an inconstant infection of the recipients and no disease transmission was observed in sheep that received cryo-precipitated fraction or supernatant obtained from infectious plasma. Despite their high efficacy, LD and LD/PR filtration of the Red Blood Cells concentrate did not provide absolute protection from infection. These results support the view that leuco-depletion strongly mitigates the v-CJD blood borne transmission risk and provide information about the relative benefits of prion reduction filters.

Figure 1. Design of blood products preparation and filtration process.

600 mL to 700 mL of whole blood were collected at the late stage of preclinical incubation from 15 VRQ/VRQ sheep orally inoculated with PG127 scrapie isolate. Blood from 3 sheep were pooled in a single pouch in order to obtain a volume higher than 1800 mL. Each pool was split into 5 parts that were individually processed according to the standard procedure applied in transfusion medicine. Obtained fractions were transfused or intravenously administered to TSE free VRQ/VRQ sheep, within five days following the blood collection. LD: leuco-depletion – LD/PR: leuco-depletion/Prion reduction. *:SEPACELL PURE RC (ASAHI). **: Plasma Filter Fenwal. ***: plasma for titration and cryoprecipitation study.