Reexamination of the chromium-51–labeled posttransfusion red blood cell recovery method
Richard O. Francis
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Equal contribution to this work.Search for more papers by this authorSonia Mahajan
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Equal contribution to this work.Search for more papers by this authorFrancesca Rapido
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Pôle Neuroscience Tête et Cou, Département d'Anesthésie -Réanimation Hôpital Gui de Chauliac- Centre Hospitalier Universitaire, Montpellier, France
Search for more papers by this authorFrancesca La Carpia
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorMark Soffing
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorChaitanya Divgi
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorRandy Yeh
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorAkiva Mintz
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorLenhurst Leslie
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorIrina Agrest
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorMatthew S. Karafin
Versiti Medical Sciences Institute, Milwaukee, Wisconsin
Search for more papers by this authorYelena Ginzburg
Division of Hematology Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
Search for more papers by this authorSteven L. Spitalnik
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorJoseph Schwartz
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorTiffany Thomas
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorPascal Amireault
Biologie Intégrée du Globule Rouge UMR_S1134, INSERM, Univ. Paris Diderot, Sorbonne Paris Cité, Univ. de la Réunion, Univ. des Antilles, Institut National de la Transfusion Sanguine, Laboratory of Excellence GR-Ex, Paris, France
Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications U1163/CNRS ERL 8254, INSERM, CNRS, Univ Paris Descartes, Sorbonne Paris Cité, Paris, France
Search for more papers by this authorPierre Buffet
Biologie Intégrée du Globule Rouge UMR_S1134, INSERM, Univ. Paris Diderot, Sorbonne Paris Cité, Univ. de la Réunion, Univ. des Antilles, Institut National de la Transfusion Sanguine, Laboratory of Excellence GR-Ex, Paris, France
Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Search for more papers by this authorAngelo D'Alessandro
University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado
Search for more papers by this authorCorresponding Author
Eldad A. Hod
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Address reprint requests to: Dr. Eldad A. Hod, Columbia University Medical Center, 630 West 168th Street, P&S 14-434 New York, NY 10032; e-mail: [email protected].Search for more papers by this authorRichard O. Francis
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Equal contribution to this work.Search for more papers by this authorSonia Mahajan
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Equal contribution to this work.Search for more papers by this authorFrancesca Rapido
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Pôle Neuroscience Tête et Cou, Département d'Anesthésie -Réanimation Hôpital Gui de Chauliac- Centre Hospitalier Universitaire, Montpellier, France
Search for more papers by this authorFrancesca La Carpia
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorMark Soffing
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorChaitanya Divgi
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorRandy Yeh
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorAkiva Mintz
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorLenhurst Leslie
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorIrina Agrest
Nuclear Medicine, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorMatthew S. Karafin
Versiti Medical Sciences Institute, Milwaukee, Wisconsin
Search for more papers by this authorYelena Ginzburg
Division of Hematology Oncology, Icahn School of Medicine at Mount Sinai, New York, New York
Search for more papers by this authorSteven L. Spitalnik
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorJoseph Schwartz
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorTiffany Thomas
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Search for more papers by this authorPascal Amireault
Biologie Intégrée du Globule Rouge UMR_S1134, INSERM, Univ. Paris Diderot, Sorbonne Paris Cité, Univ. de la Réunion, Univ. des Antilles, Institut National de la Transfusion Sanguine, Laboratory of Excellence GR-Ex, Paris, France
Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications U1163/CNRS ERL 8254, INSERM, CNRS, Univ Paris Descartes, Sorbonne Paris Cité, Paris, France
Search for more papers by this authorPierre Buffet
Biologie Intégrée du Globule Rouge UMR_S1134, INSERM, Univ. Paris Diderot, Sorbonne Paris Cité, Univ. de la Réunion, Univ. des Antilles, Institut National de la Transfusion Sanguine, Laboratory of Excellence GR-Ex, Paris, France
Université Paris Descartes, Sorbonne Paris Cité, Paris, France
Search for more papers by this authorAngelo D'Alessandro
University of Colorado Denver-Anschutz Medical Campus, Aurora, Colorado
Search for more papers by this authorCorresponding Author
Eldad A. Hod
Pathology and Cell Biology, Columbia University Irving Medical Center-New York Presbyterian Hospital, New York, New York
Address reprint requests to: Dr. Eldad A. Hod, Columbia University Medical Center, 630 West 168th Street, P&S 14-434 New York, NY 10032; e-mail: [email protected].Search for more papers by this authorAbstract
BACKGROUND
The chromium-51–labeled posttransfusion recovery (PTR) study has been the gold-standard test for assessing red blood cell (RBC) quality. Despite guiding RBC storage development for decades, it has several potential sources for error.
METHODS
Four healthy adult volunteers each donated an autologous, leukoreduced RBC unit, aliquots were radiolabeled with technetium-99m after 1 and 6 weeks of storage, and then infused. Subjects were imaged by single-photon-emission computed tomography immediately and 4 hours after infusion. Additionally, from subjects described in a previously published study, adenosine triphosphate levels in transfusates infused into 52 healthy volunteers randomized to a single autologous, leukoreduced, RBC transfusion after 1, 2, 3, 4, 5, or 6 weeks of storage were correlated with PTR and laboratory parameters of hemolysis.
RESULTS
Evidence from one subject imaged after infusion of technetium-99m–labeled RBCs suggests that, in some individuals, RBCs may be temporarily sequestered in the liver and spleen immediately following transfusion and then subsequently released back into circulation; this could be one source of error leading to PTR results that may not accurately predict the true quantity of RBCs cleared by intra- and/or extravascular hemolysis. Indeed, adenosine triphosphate levels in the transfusates correlated more robustly with measures of extravascular hemolysis in vivo (e.g., serum iron, indirect bilirubin, non–transferrin-bound iron) than with PTR results or measures of intravascular hemolysis (e.g., plasma free hemoglobin).
CONCLUSIONS
Sources of measurement error are inherent in the chromium-51 PTR method. Transfusion of an entire unlabeled RBC unit, followed by quantifying extravascular hemolysis markers, may more accurately measure true posttransfusion RBC recovery.
CONFLICT OF INTEREST
ROF, SM, FR, FLC, MS, CD, RY, AM, LL, IA, YG, BHS, JS, TT, XF, PA, PB, and EAH have disclosed no conflicts of interest. Unrelated to the contents of the manuscript, AD is the founder of Omix Technologies, Inc. and a consultant for Hemanext, Inc. MSK received a lecture honorarium from Hemanext, Inc. SLS is on the scientific advisory board of Hemanext, Inc. and is a consultant for Tioma, Inc. JCZ is on the scientific advisory board of Rubius Therapeutics.
REFERENCES
- 1Dumont LJ, AuBuchon JP. Evaluation of proposed FDA criteria for the evaluation of radiolabeled red cell recovery trials. Transfusion 2008; 48: 1053-60.
- 2Hess JR, Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Scientific problems in the regulation of red blood cell products. Transfusion 2012; 52: 1827-35.
- 3Roussel C, Buffet PA, Amireault P. Measuring post-transfusion recovery and survival of red blood cells: strengths and weaknesses of chromium-51 labeling and alternative methods. Front Med (Lausanne) 2018; 5: 130.
- 4Gaye A, Peakman T, Tobin MD, et al. Understanding the impact of pre-analytic variation in haematological and clinical chemistry analytes on the power of association studies. Int J Epidemiol 2014; 43: 1633-44.
- 5Tinmouth A, Fergusson D, Yee IC, et al. Clinical consequences of red cell storage in the critically ill. Transfusion 2006; 46: 2014-27.
- 6Zimring JC. Established and theoretical factors to consider in assessing the red cell storage lesion. Blood 2015; 125: 2185-90.
- 7Akerblom O, de Verdier CH, Finnson M, et al. Further studies on the effect of adenine in blood preservation. Transfusion 1967; 7: 1-9.
- 8Nakao K, Wada T, Kamiyama T, et al. A direct relationship between adenosine triphosphate-level and in vivo viability of erythrocytes. Nature 1962; 194: 877-8.
- 9Simon ER, Chapman RG, Finch CA. Adenine in red cell preservation. J Clin Invest 1962; 41: 351-9.
- 10van Wijk R, van Solinge WW. The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis. Blood 2005; 106: 4034-42.
- 11Dumont LJ, D'Alessandro A, Szczepiorkowski ZM, et al. CO2-dependent metabolic modulation in red blood cells stored under anaerobic conditions. Transfusion 2016; 56: 392-403.
- 12Hess JR. Measures of stored red blood cell quality. Vox Sang 2014; 107: 1-9.
- 13Van't Erve TJ, Wagner BA, Martin SM, et al. The heritability of hemolysis in stored human red blood cells. Transfusion 2015; 55: 1178-85.
- 14Crome P, Mollison PL. Splenic destruction of Rh-sensitized, and of heated red cells. Br J Haematol 1964; 10: 137-54.
- 15MacDonald A, Burrell S. Infrequently performed studies in nuclear medicine: part 1. J Nucl Med Technol 2008; 36: 132-43 quiz 145.
- 16Alvarez R, Diehl KM, Avram A, et al. Localization of splenosis using 99mTc-damaged red blood cell SPECT/CT and intraoperative gamma probe measurements. Eur J Nucl Med Mol Imaging 2007; 34: 969.
- 17Rapido F, Brittenham GM, Bandyopadhyay S, et al. Prolonged red cell storage before transfusion increases extravascular hemolysis. J Clin Invest 2017; 127: 375-82.
- 18Moroff G, Sohmer PR, Button LN. Proposed standardization of methods for determining the 24-hour survival of stored red cells. Transfusion 1984; 24: 109-14.
- 19Hod EA, Brittenham GM, Billote GB, et al. Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron. Blood 2011; 118: 6675-82.
- 20Hod EA, Zhang N, Sokol SA, et al. Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation. Blood 2010; 115: 4284-92.
- 21de Swart L, Hendriks JC, van der Vorm LN, et al. Second international round robin for the quantification of serum non-transferrin-bound iron and labile plasma iron in patients with iron-overload disorders. Haematologica 2016; 101: 38-45.
- 22Moore GL, Ledford ME, Merydith A. A micromodification of the Drabkin hemoglobin assay for measuring plasma hemoglobin in the range of 5 to 2000 mg/dl. Biochem Med 1981; 26: 167-73.
- 23Nemkov T, Sun K, Reisz JA, et al. Hypoxia modulates the purine salvage pathway and decreases red blood cell and supernatant levels of hypoxanthine during refrigerated storage. Haematologica 2018; 103: 361-72.
- 24D'Alessandro A, Reisz JA, Culp-Hill R, et al. Metabolic effect of alkaline additives and guanosine/gluconate in storage solutions for red blood cells. Transfusion 2018; 58: 1992-2002.
- 25Lachant NA, Noble NA, Myrhe BA, et al. Antioxidant metabolism during blood storage and its relationship to posttransfusion red cell survival. Am J Hematol 1984; 17: 237-49.
- 26Schreiber AD, Frank MM. Role of antibody and complement in the immune clearance and destruction of erythrocytes. I. in vivo effects of IgG and IgM complement-fixing sites. J Clin Invest 1972; 51: 575-82.
- 27Schreiber AD, Frank MM. Role of antibody and complement in the immune clearance and destruction of erythrocytes. II. Molecular nature of IgG and IgM complement-fixing sites and effects of their interaction with serum. J Clin Invest 1972; 51: 583-9.
- 28Wright SD, Silverstein SC. Tumor-promoting phorbol esters stimulate C3b and C3b' receptor-mediated phagocytosis in cultured human monocytes. J Exp Med 1982; 156: 1149-64.
- 29Vachon E, Martin R, Kwok V, et al. CD44-mediated phagocytosis induces inside-out activation of complement receptor-3 in murine macrophages. Blood 2007; 110: 4492-502.
- 30Wadenvik H, Kutti J. The spleen and pooling of blood cells. Eur J Haematol 1988; 41: 1-5.
- 31Sahin I, Reagan JL, Niroula R, et al. Refractoriness to red blood cell transfusion therapy due to hypersplenism. Transfusion 2018; 58: 2513-6.
- 32Hurford WE, Hochachka PW, Schneider RC, et al. Splenic contraction, catecholamine release, and blood volume redistribution during diving in the Weddell seal. J Appl Physiol 1996; 80: 298-306.
- 33Hurford WE, Hong SK, Park YS, et al. Splenic contraction during breath-hold diving in the Korean ama. J Appl Physiol 1990; 69: 932-6.
- 34Ilardo MA, Moltke I, Korneliussen TS, et al. Physiological and genetic adaptations to diving in sea nomads. Cell 2018; 173: 569.e515-80.e515.
- 35Stewart IB, Warburton DE, Hodges AN, et al. Cardiovascular and splenic responses to exercise in humans. J Appl Physiol 2003; 94: 1619-26.
- 36Bakovic D, Eterovic D, Saratlija-Novakovic Z, et al. Effect of human splenic contraction on variation in circulating blood cell counts. Clin Exp Pharmacol Physiol 2005; 32: 944-51.
- 37Sennels HP, Jorgensen HL, Goetze JP, et al. Rhythmic 24-hour variations of frequently used clinical biochemical parameters in healthy young males--the Bispebjerg study of diurnal variations. Scand J Clin Lab Invest 2012; 72: 287-95.
- 38Larsson A, Hassan M, Ridefelt P, et al. Circadian variability of bilirubin in healthy men during normal sleep and after an acute shift of sleep. Chronobiol Int 2009; 26: 1613-21.
- 39Dumont LJ, Yoshida T, AuBuchon JP. Anaerobic storage of red blood cells in a novel additive solution improves in vivo recovery. Transfusion 2009; 49: 458-64.
- 40Heaton WA. Evaluation of posttransfusion recovery and survival of transfused red cells. Transfus Med Rev 1992; 6: 153-69.
- 41Holt JT, Spitalnik SL, McMican AE, et al. A technetium-99m red cell survival technique for in vivo compatibility testing. Transfusion 1983; 23: 148-51.
- 42Mock DM, Widness JA, Veng-Pedersen P, et al. Measurement of posttransfusion red cell survival with the biotin label. Transfus Med Rev 2014; 28: 114-25.
- 43Szymanski IO, Valeri CR, McCallum LE, et al. Automated differential agglutination technic to measure red cell survival. I. Methodology. Transfusion 1968; 8: 65-73.
- 44Zeiler T, Muller JT, Kretschmer V. Flow-cytometric determination of survival time and 24-hour recovery of transfused red blood cells. Transfus Med Hemother 2003; 30: 14-9.
- 45Karafin MS, Bruhn R, Westlake M, et al. Demographic and epidemiologic characterization of transfusion recipients from four US regions: evidence from the REDS-III recipient database. Transfusion 2017; 57: 2903-13.
- 46Mock DM, Nalbant D, Kyosseva SV, et al. Development, validation, and potential applications of biotinylated red blood cells for posttransfusion kinetics and other physiological studies: evidenced-based analysis and recommendations. Transfusion 2018; 58: 2068-81.
Citing Literature
