PRISM
The PRISM study is now complete.
Trial of prion-filtered vs standard red cells in surgical and multi-transfused patients
Chief investigators: Dr Lorna Williamson and Dr Dupe Elebute
Primary sponsor: NHS Blood and Transplan and the Scottish National Blood Transfusion Service
Funder: NHS Blood and Transplant (NHSBT), Scottish National Blood Transfusion Service (SNBTS), Welsh Blood Service (WBS) and the Northern Ireland Blood Transfusion Service (NIBTS)
Summary
The occurrence of three cases of transfusion-transmitted variant Creutzfeldt-Jacob disease (vCJD) and a fourth transmission diagnosed post-mortem raised concerns over the safety of the UK blood supply because prion transmission by asymptomatic donors could result in a secondary vCJD outbreak.
In the absence of a screening test that could be applied to blood donors, a number of steps have been implemented over the last 10–15 years to minimize the risk of vCJD transfusion transmission, including steps to increase appropriate blood usage, and leucocyte depletion (LD) of all blood components.
However, animal studies have shown that the current generation of leucocyte reduction filters may not be fully effective in preventing vCJD transmission, removing only about 40% of the total human transmissible spongiform encephalopathy (TSE) infectivity in endogenously infected blood.
As the primary vCJD outbreak declines, secondary transmission via transfusion becomes an increasingly important factor in determining the extent and duration of the overall UK epidemic.
A red cell filter device, P-Capt (Macopharma, Tourcoing, France), incorporating a specific resin designed to remove prions (Gregori et al, 2006), the infectious agent in blood thought to cause vCJD, was CE marked in Europe in 2006.
Study hypothesis
This study evaluated the clinical safety of red cells filtered through a CE-marked prion removal filter (P-Capt).
Study design
Surgical and medical 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 concentrates (RCC) or prion-filtered red cell concentrates (PF-RCC) at eight weeks and six months post-transfusion.
Patients who received at least one unit of PF-RCC were compared with a control cohort given RCC only. Approximately 270 patients were assigned to each arm.
Findings
Approximately 917 PF-RCC and 1336 RCC units were transfused into 299 and 291 patients respectively.
26 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.
Publications
Elebute MO, Choo L, Mora A, MacRury C, Llewelyn C, Purohit S, Hicks V, Casey C, Malfroy M, Deary A, Reed T, Meredith S, Manson L, Williamson LM. Transfusion of prion-filtered red cells does not increase rate of alloimmunisation or transfusion reactions in surgical patients (PRISM A). Br J Haematol 2013; 160 (5) 701-8 [Epub 07 Jan 2013 doi: 10.1111/bjh.12188]