Original article

Vol. 22 No. 4 (2024): Blood Transfusion 4-2024 (July-August)

Ultraviolet light and riboflavin accelerates red blood cell dysfunction in vitro and in a guinea pig transfusion model

Authors

Key words: blood safety, pathogen reduction, red blood cells, animal models

Abstract

Background - Quality assessment of modified or processed red blood cell (RBC) components, such as pathogen-reduced RBCs, using only in vitro testing may not always be predictive of in vivo performance. Mouse or rat in vivo models are limited by a lack of applicability to certain aspects of human RBC biology. Here, we used a guinea pig model to study the effects of riboflavin combined with UV light on the integrity of RBCs in vitro and following transfusion in vivo.   

Materials and methods – Guinea pig RBCs were collected from WB treated with varying UV doses (10, 20, 40 or 80 J/mL) in the presence of riboflavin (UVR-RBCs). In vitro tests for UVR-RBCs included hemolysis, osmotic fragility, and cellular morphology by scanning electron microscopy. Guinea pigs transfused with one-day post-treatment UVR-RBCs were evaluated for plasma hemoglobin (Hb), non-transferrin bound iron (NTBI), total iron and Perls-detectable hemosiderin deposition in the spleen and kidney, and renal uptake of Hb.

Results - Acute RBC injury was dose dependently accelerated after treatment with UV light in the presence of riboflavin. Aberrant RBC morphology was evident at 20, 40, and 80 J/mL, and membrane lysis with Hb release was prominent at 80 J/mL. Guinea pigs transfused with 40 and 80 J/mL UVR-RBCs showed increased plasma Hb levels, and plasma NTBI was elevated in all UVR-RBC groups (10-80 J/mL). Total iron levels and Perls-hemosiderin staining in spleen and kidney as well as Hb uptake in renal proximal tubules were increased 8 hours post-transfusion with 40 and 80 J/mL UVR-RBCs.    

Discussion - UVR-RBCs administered to guinea pigs increased markers of intravascular and extravascular hemolysis in a UV dose-dependent manner. This model may allow for the discrimination of RBC injury during testing of extensively processed RBCs intended for transfusion.

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Authors

Jin Hyen Baek - Laboratory of Biochemistry and Vascular Biology, Division of Blood Components and Devices, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States of America

Hye Kyung H. Shin - Laboratory of Biochemistry and Vascular Biology, Division of Blood Components and Devices, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States of America

Fei Xu - Laboratory of Cellular Hematology, Division of Blood Components and Devices, CBER, FDA, Silver Spring, MD, United States of America

Xiaoyuan Zhang - Laboratory of Biochemistry and Vascular Biology, Division of Blood Components and Devices, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States of America

Matthew C. Williams - Laboratory of Biochemistry and Vascular Biology, Division of Blood Components and Devices, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States of America

Yamei Gao - Division of Viral Products, CBER, FDA, Silver Spring, MD, United States of America

Jaroslav G. Vostal - Laboratory of Cellular Hematology, Division of Blood Components and Devices, CBER, FDA, Silver Spring, MD, United States of America

Paul W. Buehler - University of Maryland School of Medicine, Center for Blood Oxygen Transport and Hemostasis and the Department of Pathology, Baltimore, MD, United States of America

Carlos Villa - Office of Blood Research and Review, CBER, FDA, Silver Spring, MD, United States of America

Felice D'Agnillo - Laboratory of Biochemistry and Vascular Biology, Division of Blood Components and Devices, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, MD, United States of America

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