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Transfusion. 2018 Aug;58(8):2068-2081. doi: 10.1111/trf.14647. Epub 2018 May 16.

Development, validation, and potential applications of biotinylated red blood cells for posttransfusion kinetics and other physiological studies: evidenced-based analysis and recommendations.

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Department of Biochemistry & Molecular Biology and the Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Stead Family Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa.
Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa College of Pharmacy, Iowa City, Iowa.
Laboratory of Experimental Intensive Care and Anesthesia, Academic Medical Center, Amsterdam, the Netherlands.
Department of Intensive Care, Academic Medical Center, Amsterdam, the Netherlands.
Sanquin Blood Supply, Department of Blood Cell Research, Sanquin Research, Amsterdam, the Netherlands.
Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa.
Hoxworth Blood Center and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio.
Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.


The current reference method in the United States for measuring in vivo population red blood cell (RBC) kinetics utilizes chromium-51 (51 Cr) RBC labeling for determining RBC volume, 24-hour posttransfusion RBC recovery, and long-term RBC survival. Here we provide evidence supporting adoption of a method for kinetics that uses the biotin-labeled RBCs (BioRBCs) as a superior, versatile method for both regulatory and investigational purposes. RBC kinetic analysis using BioRBCs has important methodologic, analytical, and safety advantages over 51 Cr-labeled RBCs. We critically review recent advances in labeling human RBCs at multiple and progressively lower biotin label densities for concurrent, accurate, and sensitive determination of both autologous and allogeneic RBC population kinetics. BioRBC methods valid for RBC kinetic studies, including successful variations used by the authors, are presented along with pharmacokinetic modeling approaches for the accurate determination of RBC pharmacokinetic variables in health and disease. The advantages and limitations of the BioRBC method-including its capability of determining multiple BioRBC densities simultaneously in the same individual throughout the entire RBC life span-are presented and compared with the 51 Cr method. Finally, potential applications and limitations of kinetic BioRBC determinations are discussed.

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