Reticulocytes and Related Parameters in Clinical Practice
DOI:
https://doi.org/10.6000/1929-4247.2024.13.01.2Keywords:
Reticulocytes, IRF, RMI, anemia, erythropoietic activity, hemoglobin, Ret-He, CHrAbstract
The development of hematologic analyzers allowed us to assess several additional parameters derived in addition to the number of reticulocytes. There is, among others, the calculation of immature reticulocyte fractions, reticulocyte maturity index, reticulocyte production index, and equivalent reticulocyte hemoglobin. The advantage of the equivalent hemoglobin and the content of hemoglobin is the insensitivity to interference by inflammation. These newly introduced parameters expand the possibilities to access bone marrow erythropoietic activity, iron stores, and the effectiveness of iron supplementation, vitamin B12, and folic acid supplementation. These parameters are also used to make decisions about blood transfusions or to detect occult internal bleeding.
References
Mei Y, Liu Y, Ji P. Understanding terminal erythropoiesis: An update on chromatin condensation, enucleation, and reticulocyte maturation. Blood Rev 2021; 46: 100740. https://doi.org/10.1016/j.blre.2020.100740 DOI: https://doi.org/10.1016/j.blre.2020.100740
Baldini M, Pannacciulli I. The maturation rate of reticulocytes. Blood 1960; 15: 614-29. https://doi.org/10.1182/blood.V15.5.614.614 DOI: https://doi.org/10.1182/blood.V15.5.614.614
Bender MA, Carlberg K. Sickle cell disease 2003 Sep 15 [updated 2023 Dec 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024.
Pan LL, Yu HC, Lee CH, Hung KC, Tsai IT, Sun CK. Impact of staining methods and human factors on the accuracy of manual reticulocyte enumeration. Diagnostics (Basel) 2022; 12(9): 2154. https://doi.org/10.3390/diagnostics12092154 DOI: https://doi.org/10.3390/diagnostics12092154
Lacombe F, Lacoste L, Vial JP, Briais A, et al. Automated reticulocyte counting and immature reticulocyte fraction measurement. Comparison of ABX PENTRA 120 Retic, Sysmex R-2000, flow cytometry, and manual counts. Am J Clin Pathol 1999; 112(5): 677-86. https://doi.org/10.1093/ajcp/112.5.677 DOI: https://doi.org/10.1093/ajcp/112.5.677
George L, Basu D, Kar R. Comparison between manual and automated methods of counting reticulocytes and the effect of sample storage on reticulocyte count: a cross-sectional study from Southern India. Indian J Hematol Blood Transfus 2022; 38(1): 106-110. https://doi.org/10.1007/s12288-021-01424-x DOI: https://doi.org/10.1007/s12288-021-01424-x
Ibrahim H, Nadipalli S, Usmani S, DeLao T, Green L, Kleiman NS. Detection and quantification of circulating immature platelets: agreement between flow cytometric and automated detection. J Thromb Thrombolysis 2016; 42(1): 77-83. https://doi.org/10.1007/s11239-016-1338-3 DOI: https://doi.org/10.1007/s11239-016-1338-3
Koury MJ, Koury ST, Kopsombut P, Bondurant MC. In vitro maturation of nascent reticulocytes to erythrocytes. Blood 2005; 105(5): 2168-74. https://doi.org/10.1182/blood-2004-02-0616 DOI: https://doi.org/10.1182/blood-2004-02-0616
Buttarello M, Bulian P, Farina G, Petris MG, Temporin V, Toffolo L. Five fully automated methods for performing immature reticulocyte fraction: comparison in diagnosis of bone marrow aplasia. Am J Clin Pathol 2002; 117(6): 871-9. https://doi.org/10.1309/VJAA-L52P-FGRM-QGRU DOI: https://doi.org/10.1309/VJAA-L52P-FGRM-QGRU
Shapiro HM, Stephens S. Flow cytometry of DNA content using oxazine 750 or related laser dyes with 633 nm excitation. Cytometry 1986; 7(1): 107-10. https://doi.org/10.1002/cyto.990070118 DOI: https://doi.org/10.1002/cyto.990070118
Obstfeld AE, Davis BH, Han JY, Urrechaga E. Report of the International Council for Standardization in Haematology working group for standardization of reticulocyte parameters. Int J Lab Hematol 2023. https://doi.org/10.1111/ijlh.14209 DOI: https://doi.org/10.1111/ijlh.14209
Borrione P, Spaccamiglio A, Parisi A, et al. A biparametric flow cytometry analysis for the study of reticulocyte patterns of maturation. Int J Lab Hematol 2010; 32(1 Pt 2): 65-73. https://doi.org/10.1111/j.1751-553X.2008.01128.x DOI: https://doi.org/10.1111/j.1751-553X.2008.01128.x
Hillman RS, Adamson J, Burka E. Characteristics of vitamin B12 correction of the abnormal erythropoiesis of pernicious anemia. Blood 1968; 31(4): 419-32. https://doi.org/10.1182/blood.V31.4.419.419 DOI: https://doi.org/10.1182/blood.V31.4.419.419
Andrès E, Kaltenbach G, Noel E, et al. Efficacy of short-term oral cobalamin therapy for the treatment of cobalamin deficiencies related to food-cobalamin malabsorption: a study of 30 patients. Clin Lab Haematol 2003; 25(3): 161-6. https://doi.org/10.1046/j.1365-2257.2003.00515.x DOI: https://doi.org/10.1046/j.1365-2257.2003.00515.x
Gomez-Pomar E, Hatfield E, Garlitz K, Westgate PM, Bada HS. Vitamin E in the preterm infant: a forgotten cause of hemolytic anemia. Am J Perinatol 2018; 35(3): 305-310. https://doi.org/10.1055/s-0037-1607283 DOI: https://doi.org/10.1055/s-0037-1607283
Priya PP, ARS. Role of absolute reticulocyte count in evaluation of pancytopenia-a hospital based study. J Clin Diagn Res 2014; 8(8): FC01-3. https://doi.org/10.7860/JCDR/2014/8949.4704 DOI: https://doi.org/10.7860/JCDR/2014/8949.4704
Wang M. Iron deficiency and other types of anemia in infants and children. Am Fam Physician 2016; 93(4): 270-8.
El-Lahony DM, Saleh NY, Habib MS, Shehata MA, El-Hawy MA. The role of recombinant Human erythropoietin in neonatal anemia. Hematol Oncol Stem Cell Ther 2020; 13(3): 147-151. https://doi.org/10.1016/j.hemonc.2019.08.004 DOI: https://doi.org/10.1016/j.hemonc.2019.08.004
Fauchère JC, Koller BM, Tschopp A, Dame C, Ruegger C, Bucher HU; Swiss erythropoietin neuroprotection trial group. Safety of early high-dose recombinant erythropoietin for neuroprotection in very preterm infants. J Pediatr 2015; 167(1): 52-7.e1-3. https://doi.org/10.1016/j.jpeds.2015.02.052 DOI: https://doi.org/10.1016/j.jpeds.2015.02.052
Yamada M, Chishiki M, Kanai Y, Goto A, Imamura T. Neonatal reticulocyte count during the early postnatal period. Pediatr Neonatol 2020; 61(5): 490-497. https://doi.org/10.1016/j.pedneo.2020.04.004 DOI: https://doi.org/10.1016/j.pedneo.2020.04.004
Khurana R, Batra P, Faridi M, Khan N. Revisiting ABO incompatibility as a risk factor for significant neonatal hyperbilirubinemia. Trop Doct 2019; 49(3): 201-204. https://doi.org/10.1177/0049475519838428 DOI: https://doi.org/10.1177/0049475519838428
Herzlich J, Litmanovitz I, Regev R, et al. Iron homeostasis after blood transfusion in stable preterm infants - an observational study. J Perinat Med 2016; 44(8): 919-923. https://doi.org/10.1515/jpm-2015-0361 DOI: https://doi.org/10.1515/jpm-2015-0361
Narli N, Satar M, Atici A, Kayrin L. Erythrocyte pyruvate kinase activity in term and preterm infants. Pediatr Hematol Oncol 1998; 15(1): 63-7. https://doi.org/10.3109/08880019809009509 DOI: https://doi.org/10.3109/08880019809009509
Qiao L, Tang Q, Zhu W, Zhang H, Zhu Y, Wang H. Effects of early parenteral iron combined erythropoietin in preterm infants: A randomized controlled trial. Medicine (Baltimore) 2017; 96(9): e5795. https://doi.org/10.1097/MD.0000000000005795 DOI: https://doi.org/10.1097/MD.0000000000005795
Stripeli F, Kapetanakis J, Gourgiotis D, Drakatos A, Tsolia M, Kossiva L. Post-transfusion changes in serum hepcidin and iron parameters in preterm infants. Pediatr Int 2018; 60(2): 148-152. https://doi.org/10.1111/ped.13478 DOI: https://doi.org/10.1111/ped.13478
Geldard AR, Tobin DJ, Cuthbert A. Immature reticulocyte fraction as a useful parameter for blood transfusion assessment in anaemia. Br J Biomed Sci 2009; 66(2): 98-101. https://doi.org/10.1080/09674845.2009.11730252 DOI: https://doi.org/10.1080/09674845.2009.11730252
Watanabe K, Kawai Y, Takeuchi K, et al. Reticulocyte maturity as an indicator for estimating qualitative abnormality of erythropoiesis. J Clin Pathol 1994; 47(8): 736-9. https://doi.org/10.1136/jcp.47.8.736 DOI: https://doi.org/10.1136/jcp.47.8.736
Mitrani R, Gollomp K, Lambert MP, Obstfeld A. The Immature reticulocyte fraction as an aid in the diagnosis and prognosis of parvovirus B19 infection in sickle cell disease. Blood 2018; 132(Supplement 1): 3678-3678. https://doi.org/10.1182/blood-2018-99-117152 DOI: https://doi.org/10.1182/blood-2018-99-117152
Rauf SE, Khan SA, Ali N, Afridi NK, Haroon M, Arslan A. Immature reticulocyte fraction and absolute neutrophil count as predictor of hemopoietic recovery in patients with acute lymphoblastic leukemia on remission induction chemotherapy. Turk J Haematol 2016; 33(2): 131-4. https://doi.org/10.4274/tjh.2014.0379 DOI: https://doi.org/10.4274/tjh.2014.0379
Yesmin S, Sultana T, Roy CK, Rahman MQ, Ahmed AN. Immature reticulocyte fraction as a predictor of bone marrow recovery in children with acute lymphoblastic leukaemia on remission induction phase. Bangladesh Med Res Counc Bull 2011; 37(2): 57-60. https://doi.org/10.3329/bmrcb.v37i2.8435 DOI: https://doi.org/10.3329/bmrcb.v37i2.8435
Mohammadi S, Jalili M, Malek Mohammadi A, et al. An alternative test for determining autologous stem cell transplantation cell harvesting outcome: Comparison between predictive values of two tests. Transfus Apher Sci 2020; 59(4): 102763. https://doi.org/10.1016/j.transci.2020.102763 DOI: https://doi.org/10.1016/j.transci.2020.102763
Morkis IV, Farias MG, Rigoni LD, et al. Assessment of immature platelet fraction and immature reticulocyte fraction as predictors of engraftment after hematopoietic stem cell transplantation. Int J Lab Hematol 2015; 37(2): 259-64. https://doi.org/10.1111/ijlh.12278 DOI: https://doi.org/10.1111/ijlh.12278
Wickramaratne KAC, Wijegunawardena JKD, Wijewickrama DC. Manual immature reticulocyte fraction; a surrogate marker to assess post-traumatic blood loss. Gall Med J 2021; 26(4): 158. https://doi.org/10.4038/gmj.v26i4.8112 DOI: https://doi.org/10.4038/gmj.v26i4.8112
Ahmed T, Mahmood A, Uddin N, Robert HM, Mahmood R, Swati UT. Diagnostic significance of measuring reticulocyte maturity indices in iron deficiency anaemia. Pakistan Armed Forces Med J 2021; 71(6): 2109-13. https://doi.org/10.51253/pafmj.v71i6.5642 DOI: https://doi.org/10.51253/pafmj.v71i6.5642
Davis BH, DiCorato M, Bigelow NC, Langweiler MH. Proposal for standardization of flow cytometric reticulocyte maturity index (RMI) measurements. Cytometry 1993; 14(3): 318-26. https://doi.org/10.1002/cyto.990140312 DOI: https://doi.org/10.1002/cyto.990140312
Choi JW, Pai SH. Reticulocyte subpopulations and reticulocyte maturity index (RMI) rise as body iron status falls. Am J Hematol 2001; 67(2): 130-5. https://doi.org/10.1002/ajh.1091 DOI: https://doi.org/10.1002/ajh.1091
Davis BH, Ornvold K, Bigelow NC. Flow cytometric reticulocyte maturity index: a useful laboratory parameter of erythropoietic activity in anemia. Cytometry 1995; 22(1): 35-9. https://doi.org/10.1002/cyto.990220107 DOI: https://doi.org/10.1002/cyto.990220107
Hillman RS. Characteristics of marrow production and reticulocyte maturation in normal man in response to anemia. J Clin Invest 1969; 48(3): 443-53. https://doi.org/10.1172/JCI106001 DOI: https://doi.org/10.1172/JCI106001
Ng HY, Chen HC, Pan LL, et al. Clinical interpretation of reticulocyte hemoglobin content, RET-Y, in chronic hemodialysis patients. Nephron Clin Pract 2009; 111(4): c247-52. https://doi.org/10.1159/000209151 DOI: https://doi.org/10.1159/000209151
Bracho FJ, Osorio IA. Evaluation of the Reticulocyte Production Index in the Pediatric Population. Am J Clin Pathol 2020; 154(1): 70-77. https://doi.org/10.1093/ajcp/aqaa020 DOI: https://doi.org/10.1093/ajcp/aqaa020
Poventud-Fuentes I, Chong TH, Dowlin M, Devaraj S, Curry CV. Reticulocyte hemoglobin equivalent as a marker to assess iron deficiency: A large pediatric tertiary care hospital study. Int J Lab Hematol 2024; 46(1): 148-155. https://doi.org/10.1111/ijlh.14188 DOI: https://doi.org/10.1111/ijlh.14188
Chinudomwong P, Binyasing A, Trongsakul R, Paisooksantivatana K. Diagnostic performance of reticulocyte hemoglobin equivalent in assessing the iron status. J Clin Lab Anal 2020; 34(6): e23225. https://doi.org/10.1002/jcla.23225 DOI: https://doi.org/10.1002/jcla.23225
Kim JM, Ihm CH, Kim HJ. Evaluation of reticulocyte haemoglobin content as marker of iron deficiency and predictor of response to intravenous iron in haemodialysis patients. Int J Lab Hematol 2008; 30(1): 46-52. https://doi.org/10.1111/j.1751-553X.2007.00901.x DOI: https://doi.org/10.1111/j.1751-553X.2007.00901.x
Urrechaga E, Boveda O, Aguayo FJ, et al. Percentage of hypochromic erythrocytes and reticulocyte hemoglobin equivalent predictors of response to intravenous iron in hemodialysis patients. Int J Lab Hematol 2016; 38(4): 360-5. https://doi.org/10.1111/ijlh.12496 DOI: https://doi.org/10.1111/ijlh.12496
Di Pinto D, Paz M, Adragna M, López L. Clinical usefulness of the reticulocyte hemoglobin equivalent in children on hemodialysis. Arch Argent Pediatr 2020; 118(6): 411-417. English, Spanish. https://doi.org/10.5546/aap.2020.eng.411 DOI: https://doi.org/10.5546/aap.2020.eng.411
Cai J, Wu M, Ren J, et al. Evaluation of the Efficiency of the Reticulocyte Hemoglobin Content on Diagnosis for Iron Deficiency Anemia in Chinese Adults. Nutrients 2017; 9(5): 450. https://doi.org/10.3390/nu9050450 DOI: https://doi.org/10.3390/nu9050450
Mateos ME, De-la-Cruz J, López-Laso E, Valdés MD, Nogales A. Reticulocyte hemoglobin content for the diagnosis of iron deficiency. J Pediatr Hematol Oncol 2008; 30(7): 539-42. https://doi.org/10.1097/MPH.0b013e31817580ca DOI: https://doi.org/10.1097/MPH.0b013e31817580ca
Parodi E, Giraudo MT, Ricceri F, Aurucci ML, Mazzone R, Ramenghi U. Absolute Reticulocyte Count and Reticulocyte Hemoglobin Content as Predictors of Early Response to Exclusive Oral Iron in Children with Iron Deficiency Anemia. Anemia 2016; 2016: 7345835. https://doi.org/10.1155/2016/7345835 DOI: https://doi.org/10.1155/2016/7345835
Parodi E, Giraudo MT, Davitto M, et al. Reticulocyte parameters: markers of early response to oral treatment in children with severe iron-deficiency anemia. J Pediatr Hematol Oncol 2012; 34(6): e249-52. https://doi.org/10.1097/MPH.0b013e3182588996 DOI: https://doi.org/10.1097/MPH.0b013e3182588996
Kurzawa T, Owczarek A, Strzelczyk JK, Gołąbek K, Wiczkowski A. The Content of Reticulocyte Hemoglobin and Serum Concentration of the Soluble Transferrin Receptor for Diagnostics of Anemia in Chronically Hemodialyzed Patients. Adv Clin Exp Med 2016; 25(3): 425-31. https://doi.org/10.17219/acem/58786 DOI: https://doi.org/10.17219/acem/58786
Mast AE, Blinder MA, Lu Q, Flax S, Dietzen DJ. Clinical utility of the reticulocyte hemoglobin content in the diagnosis of iron deficiency. Blood 2002; 99(4): 1489-91. https://doi.org/10.1182/blood.V99.4.1489 DOI: https://doi.org/10.1182/blood.V99.4.1489
Balci YI, Akpinar FO, Polat A, Uzun U, Ergin A. Evaluation of Reticulocyte Parameters in Iron Deficiency, Vitamin B12 Deficiency and Mixed Anemia. Clin Lab 2016; 62(3): 343-7. https://doi.org/10.7754/Clin.Lab.2015.150616 DOI: https://doi.org/10.7754/Clin.Lab.2015.150616
Uçar MA, Falay M, Dağdas S, Ceran F, Urlu SM, Özet G. The Importance of RET-He in the Diagnosis of Iron Deficiency and Iron Deficiency Anemia and the Evaluation of Response to Oral Iron Therapy. J Med Biochem 2019; 38(4): 496-502. https://doi.org/10.2478/jomb-2018-0052 DOI: https://doi.org/10.2478/jomb-2018-0052
Karunarathne P, Kulathilake C, Wijesiriwardena I, Hewageegana A, Marasinghe A. Evaluation of Iron Status by Reticulocyte Haemoglobin Content (Chr) in Chronic Kidney Disease Patients on Haemodialysis and Erythropoietin. Indian J Hematol Blood Transfus 2022; 38(2): 359-365. https://doi.org/10.1007/s12288-021-01464-3 DOI: https://doi.org/10.1007/s12288-021-01464-3
Alageeli AA, Alqahtany FS, Algahtani FH. The Role of Reticulocyte Hemoglobin Content for the Diagnosis of Functional Iron Deficiency in Hemodialyzed Patients. Saudi J Biol Sci 2021; 28(1): 50-54. https://doi.org/10.1016/j.sjbs.2020.08.030 DOI: https://doi.org/10.1016/j.sjbs.2020.08.030
Huq M, Hossain R, Alam M, et al. Reticulocyte Haemoglobin Content (CHr) is a Reliable Marker of Iron Deficiency in Pre-dialytic Chronic Kidney Disease (CKD) Patients. Arch Nephrol Urol 2022; 05(02): 34-45. https://doi.org/10.26502/anu.2644-2833050 DOI: https://doi.org/10.26502/anu.2644-2833050
Almashjary MN, Barefah AS, Bahashwan S, et al. Reticulocyte Hemoglobin-Equivalent Potentially Detects, Diagnoses, and Discriminates between Stages of Iron Deficiency with High Sensitivity and Specificity. J Clin Med 2022; 11(19): 5675. https://doi.org/10.3390/jcm11195675 DOI: https://doi.org/10.3390/jcm11195675
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