Hypoxic storage of donor red cells preserves deformability after exposure to plasma from adults with sickle cell disease

Abstract

Background Red cell (RBC) transfusions are beneficial for patients with sickle cell disease (SCD), but ex vivo studies suggest that inflamed plasma from patients with SCD during crises may damage these RBCs, diminishing their potential efficacy. The hypoxic storage of RBCs may improve transfusion efficacy by minimizing the storage lesion. We tested the hypotheses that (1) The donor RBCs exposed to the plasma of patients in crisis would have lower deformability and higher hemolysis than those exposed to non‐crisis plasma, and (2) hypoxic storage, compared to standard storage, of donor RBCs could preserve deformability and reduce hemolysis. Study Design and Methods 18 SCD plasma samples from patients who had severe acute‐phase symptoms (A‐plasma; n = 9) or were at a steady‐state (S = plasma; n = 9) were incubated with 16 RBC samples from eight units that were stored either under conventional(CRBC) or hypoxic(HRBC) conditions. Hemolysis and microcapillary deformability assays of these RBCs were analyzed using linear mixed‐effect models after each sample was incubated in patient plasma overnight at 37°C Results Relative deformability was 0.036 higher (p < 0.0001) in HRBC pairs compared to CRBC pairs regardless of plasma type. Mean donor RBC hemolysis was 0.33% higher after incubation with A‐plasma compared to S‐plasma either with HRBC or CRBC (p = 0.04). HRBCs incubated with steady‐state patient plasma demonstrated the highest deformability and lowest hemolysis. Conclusion Hypoxic storage significantly influenced RBC deformability. Patient condition significantly influenced post‐incubation hemolysis. Together, HRBCs in steady‐state plasma maximized donor red cell ex vivo function and survival.

Tools and metrics for the assessment of post‐storage performance of red blood cells: no one is left over

“…Moreover, these in vitro systems can be used as screening platforms to identify candidate biomarkers of transfusion efficiency and risks, and they are useful for the quality control of storage systems and the optimization of storage strategies, following validation at transfusion‐simulating levels. Based on these perspectives, I hope the paper of Karafin et al 1 will stimulate and encourage further use of those research tools and metrics in the field of the RBC storage lesion.…”

“…This is one (among many) obstacles that can be overcome by ex vivo experimentation in donor–recipient pairs. In this context, a valuable follow‐up to the Karafin study 1 would include measuring the baseline storage (and patient) RBC deformability. Despite discrepancies in the literature, 27 treatment of stored RBCs with rejuvenation solutions leads to no 28 or only partial 29 restoration of deformability and mechanical fragility of stored RBC.…”

“…In this issue of TRANSFUSION, Karafin et al 1 report the effects of plasma from either steady‐state or acute‐phase sickle cell disease (SCD) patients on hemolysis and cell deformability of red blood cells (RBCs) following their storage under hypoxic or conventional conditions. With either type of SCD plasma, deformability as measured by a microcapillary assay was better preserved in RBCs stored under hypoxic conditions compared to standard conditions.…”

“…What can be finally argued by the study of Karafin et al 1 is the usefulness of ex vivo experiments in studying the post‐storage performance of donor RBCs under well‐defined, controlled conditions. The post‐storage performance emerges as a mixed function of donor, blood product, and recipient variables.…”

“…Significant results of these simulation experiments for various donor and recipient groups and storage strategies have revealed (i) how recipient‐related components and fluctuations or stresses may ameliorate or amplify, respectively, the storage lesion phenotypes, (ii) the impact of storage time, preservative solutions, and alternative protocols on them, and (iii) measurable information on the clinically significant interactions between the two biological materials. Karafin et al 1 showed that the clinical status of the SCD patient affects post‐storage hemolysis. Consistent with this observation, incubating donor RBCs with plasma from SCD patients having VOC crises was previously shown to increase RBC phosphatidylserine exposure 49 .…”