Infusion of P-Capt prion-filtered red blood cell products demonstrate acceptable in vivo viability and no evidence of neoantigen formation

Hoxworth Blood Center, University of Cincinnati, Cincinnati, Ohio 45267-0055, USA.
Transfusion (Impact Factor: 3.23). 04/2011; 51(10):2228-36. DOI: 10.1111/j.1537-2995.2011.03133.x
Source: PubMed


Transmission of variant Creutzfeldt-Jacob disease (vCJD) is a major concern in blood transfusion. The P-Capt filter has been shown to remove around 4 log ID(50) prion infectivity from prion-spiked human red blood cells (RBCs).
Two independent, single-center, randomized, open-label studies were designed to analyze the safety of P-Capt-filtered RBCs. RBCs prepared from leukoreduced whole blood from 43 eligible subjects were randomly assigned to P-Capt filtration and/or storage in plasma or SAGM and stored for 28 or 42 days. Stored RBCs were analyzed for in vivo 24-hour recovery, hemolysis, metabolic variables, blood group antigen expression, neoantigen formation, and safety after autologous infusion.
Mean P-Capt filtration times for leukoreduced RBCs were 41 (SAGM) to 51 (plasma) minutes. Thirteen of 14 subjects receiving P-Capt-filtered RBCs had 24-hour RBC recoveries of 75% or more after 42-day storage, with a mean hemolysis of less than 0.6%. No loss of RBC antigen expression or formation of neoantigens was observed. In both studies, RBCs had white blood cell counts of less than 1 × 10(6)/unit after leukofiltration. P-Capt prion filtration provided an additional greater than 0.8 log leukoreduction. No serious or unexpected adverse events were observed after infusion of P-Capt-filtered full-volume RBC units.
P-Capt-filtered, stored RBCs demonstrated acceptable viability and no detectable neoantigen expression, immunogenic responses. or safety issues after infusion of a complete unit. The additional filtration time and modest reduction in RBC content are within acceptable levels for implementation in countries with transfusion transmission of vCJD.

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    ABSTRACT: BACKGROUND: Variant Creutzfeldt-Jakob disease (vCJD) is a rare, progressive fatal noninflammatory neurodegenerative disease. Ireland has the second highest rate of vCJD in the world with an ongoing risk of vCJD transmission through blood transfusion. Prion-removing filters have been developed to reduce the risk of vCJD transmission. This study aimed to evaluate the cost-effectiveness of implementing a policy of prion filtration of red blood cells (RBCs) in the Republic of Ireland. STUDY DESIGN AND METHODS: A cost-effectiveness model was developed to simulate the likelihood of RBC recipients developing clinical vCJD as a result of being transfused with infected RBCs. Model variables were collected from published literature and expert opinion. Costs were estimated based on the processing changes required to implement prion filtration. RESULTS: In the absence of prion filtration, it is estimated that two individuals will develop clinical vCJD arising from RBC transfusions over a 10-year time horizon. The discounted life-years lost will be 18.5 years. With prion filtration, there will be no deaths or life-years lost. The discounted cost of universal prion filtration is €68.2 million over 10 years with a corresponding incremental cost-effectiveness ratio of €3.7 million per life-year gained. In 25.3% of simulations there were no deaths from vCJD infection through infected blood transfusions, irrespective of prion filtration. CONCLUSION: Prion filtration is considered not cost-effective by traditional measures. Although numerous non–cost-effective blood safety strategies have been implemented in the past, consideration should be given to the most efficient use of finite resources in transfusion medicine.
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    ABSTRACT: This study, conducted for the UK Blood Transfusion Services (UKBTS), evaluated the clinical safety of red cells filtered through a CE-marked prion removal filter (P-Capt™). Patients requiring blood transfusion for elective procedures in nine UK hospitals were entered into a non-randomized open trial to assess development of red cell antibodies to standard red cell (RCC) or prion-filtered red cell concentrates (PF-RCC) at eight weeks and six months post-transfusion. Patients who received at least 1 unit of PF-RCC were compared with a control cohort given RCC only. About 917 PF-RCC and 1336 RCC units were transfused into 299 and 291 patients respectively. Twenty-six new red cell antibodies were detected post-transfusion in 10 patients in each arm, an overall alloimmunization rate of 4·4%. Neither the treatment arm [odds ratio (OR) 0·93, 95% confidence interval (CI) 0·3, 2·5] nor number of units transfused (OR 0·95, 95% CI 0·8, 1·1) had a significant effect on the proportion of patients who developed new alloantibodies. No pan-reactive antibodies or antibodies specifically against PF-RCC were detected. There was no difference in transfusion reactions between arms, and no novel transfusion-related adverse events clearly attributable to PF-RCC were seen. These data suggest that prion filtration of red cells does not reduce overall transfusion safety. This finding requires confirmation in large populations of transfused patients.
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