Risks associated with red blood cell transfusions: potential benefits from application of pathogen inactivation

Abstract

Background: Red blood cell (RBC) transfusion risks could be reduced if a robust technology for pathogen inactivation of RBC (PI-RBCs) were to be approved.

Materials and methods: Estimates of per-unit and per-patient aggregate infectious risks for conventional RBCs were calculated; the latter used patient diagnosis as a determinant of estimated lifetime exposure to RBC units. Existing in vitro data for the two technologies under development for producing PI-RBCs and the status of current clinical trials are reviewed.

Results: Minimum and maximum per-unit risk were calculated as 0.0003% (1 in 323,000) and 0.12% (1 in 831), respectively. The minimum estimate is for known lower-risk pathogens while the maximal estimate also includes an emerging infectious agent (EIA) and endemic area Babesia risk. Minimum and maximum per-patient lifetime risks by diagnosis grouping were estimated as 1.5 and 3.3%, respectively, for stem cell transplantation (which includes additional risk for cytomegalovirus transmission); 1.2 and 3.7%, respectively, for myelodysplastic syndrome; and 0.2 and 44%, respectively, for hemoglobinopathy.

Discussion: There is potential for PI technologies to reduce infectious RBC risk and to provide additional benefits (e.g., prevention of transfusion-associated graft-versus-host disease and possible reduction of alloimmunization) due to white blood cell inactivation. PI-RBCs should be viewed in the context of having a fully PI-treated blood supply, enabling a blood safety paradigm shift from reactive to proactive. Providing insurance against new EIAs. Further, when approved, the use of PI for all components may catalyze operational changes in blood donor screening, laboratory testing, and component manufacturing.

Figure 1

Quantitating transfusion risk over time. In the absence of additional interventions, known per‐unit infectious risks are consistent over time. These risks change when an EIA enters the blood supply. The figure indicates two types of EIAs: an acute agent and a chronic agent.^* A past example of an acute EIA is West Nile virus and a past example of a chronic EIA is HIV. In contrast to known agents, EIA risks will vary over time. The intervals between an acute or chronic EIA entering the blood supply and the application of a successful intervention for that agent have been estimated as 1.5 and 5 years, respectively. After recognition of the EIA and development of a screening test, the risk from that agent will be decreased but a small residual risk will remain, thereby slightly increasing the overall per‐unit risk above the previous level. This is indicated (though not to scale) by the stepwise increase in the horizontal line. *An acute agent is present only transiently (usually days to weeks) until the donor resolves the viremia or parasitemia. In contrast, the donor retains the chronic agent in their blood for many years (perhaps an entire lifetime) while remaining asymptomatic and capable of blood donation.

Figure 2

CMV risk: historical data and recent studies. The graph depicts the per‐unit risk as quantified in the different publications. The circles indicate the mean values. Patient studies are grouped above and donor studies are depicted under the x‐axis. The length of the arrows corresponds to the 95% confidence intervals, when reported, or high and low estimates. The overall estimate is depicted with the vertical arrow above the x‐axis and takes into account that only the approximately 50% of patients who are CMV seronegative are at risk for acquiring TT‐CMV.

Figure 3

Conceptual approaches for PI of blood products.

Figure 4

Comparison of systems for PI of RBCs and WB.104, 105