A Meta-analysis of the Utility of Red Cell Distribution Width as a Biomarker to Predict Outcomes in Pediatric Illness (PROSPERO CRD42020208777)

Devin Murphy; Etan Orgel; Wouter Koek; Melissa Frei-Jones; Christopher Denton; Deepak Kamat

doi:10.1055/s-0041-1735876

Journal of Pediatric Intensive Care, Table of Contents

J Pediatr Intensive Care 2024; 13(04): 307-314
DOI: 10.1055/s-0041-1735876

Review Article

A Meta-analysis of the Utility of Red Cell Distribution Width as a Biomarker to Predict Outcomes in Pediatric Illness (PROSPERO CRD42020208777)

Devin Murphy

¹Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United Sates

,

Etan Orgel

²Division of Hematology, Oncology and Blood and Marrow Transplantation, Children's Hospital Los Angeles, Los Angeles, California, United Sates

³Department of Psychiatry, Keck School of Medicine, University of Southern California, Los Angeles, California, United Sates

,

Wouter Koek

¹Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United Sates

,

Melissa Frei-Jones

¹Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United Sates

⁴Department of Pediatrics, Pediatric Hematology–Oncology, Long School of Medicine, University of Texas Health Science Center San Antonio, Texas, United Sates

,

Christopher Denton

²Division of Hematology, Oncology and Blood and Marrow Transplantation, Children's Hospital Los Angeles, Los Angeles, California, United Sates

³Department of Psychiatry, Keck School of Medicine, University of Southern California, Los Angeles, California, United Sates

,

Deepak Kamat

¹Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United Sates

› Author Affiliations

Abstract

Red cell distribution width (RDW) is an average of the variation in red blood cell (RBC) sizes reported on a complete blood count. An elevated RDW indicates a pathological process that is affecting erythropoiesis. Studies showed that as the severity of disease process increases, the RDW often increases as well. Particularly in resource-limited countries, RDW has been studied as an outcome predictor for conditions in a variety of disciplines and is offered as an adjunct monitoring tool that is cost effective, readily available, and indicative of pathological processes amenable to intervention. Particularly in pediatric critical care settings, RDW has been shown to be a reliable tool for surveillance of disease states such as sepsis. Despite the increased attention of RDW as a marker for disease outcome, collective evaluation on the utility of RDW as a marker for outcome in pediatric critical care settings is lacking. We offer a systematic review and meta-analysis of published studies to assess the ability of RDW to predict illness severity and mortality among pediatric critical care patients. Among eight studies of over 4,800 patients, we found over a two-fold increase in odds for mortality in critically ill children whose RDW was above 15.7%. This is the first systematic review of RDW being used to predict mortality in critically ill children and findings of this study may prompt early intervention in the pediatric critical care setting.

Keywords

RDW - hematology - mortality - critical care - pediatric

Full Text

References

References
1 Makhoul BF, Khourieh A, Kaplan M, Bahouth F, Aronson D, Azzam ZS. Relation between changes in red cell distribution width and clinical outcomes in acute decompensated heart failure. Int J Cardiol 2013; 167 (04) 1412-1416
2 Polat V, Iscan S, Etli M. et al. Red cell distribution width as a prognostic indicator in pediatric heart disease and after surgery. BioMed Res Int 2014; 2014: 681679
3 Braun E, Domany E, Kenig Y, Mazor Y, Makhoul BF, Azzam ZS. Elevated red cell distribution width predicts poor outcome in young patients with community acquired pneumonia. Crit Care 2011; 15 (04) R194
4 Rafsanjani KA, Falahati V, Kiumarsi A. The association between red cell distribution width and mortality in pediatric acute lymphoblastic leukemia. J Neoplasm 2017; 2: 2
5 Martin SL, Desai S, Nanavati R, Colah RB, Ghosh K, Mukherjee MB. Red cell distribution width and its association with mortality in neonatal sepsis. J Matern Fetal Neonatal Med 2019; 32 (12) 1925-1930
6 Pilling LC, Atkins JL, Kuchel GA, Ferrucci L, Melzer D. Red cell distribution width and common disease onsets in 240,477 healthy volunteers followed for up to 9 years. PLoS One 2018; 13 (09) e0203504
7 Patel KV, Ferrucci L, Ershler WB, Longo DL, Guralnik JM. Red blood cell distribution width and the risk of death in middle-aged and older adults. Arch Intern Med 2009; 169 (05) 515-523
8 Mehta NM, Duggan CP. Nutritional deficiencies during critical illness. Pediatr Clin North Am 2009; 56 (05) 1143-1160
9 Haddaway NR, Collins AM, Coughlin D, Kirk S. The role of Google Scholar in evidence reviews and its applicability to grey literature searching. PLoS One 2015; 10 (09) e0138237
10 Wong WC, Cheung CS, Hart GJ. Development of a quality assessment tool for systematic reviews of observational studies (QATSO) of HIV prevalence in men having sex with men and associated risk behaviours. Emerg Themes Epidemiol 2008; 5: 23
11 Munn Z, Moola S, Lisy K, Riitano D, Tufanaru C. Methodological guidance for systematic reviews of observational epidemiological studies reporting prevalence and cumulative incidence data. Int J Evid-Based Healthc 2015; 13 (03) 147-153
12 Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw 2010; 36: 1-48
13 Khanbabaee G, Hashemi SM, Salarian S, Fariborzi MR, Kiumarsi A. Red cell distribution width elevation and sepsis in pediatric critically ill patients. Arch Pediatr Infect Dis 2018; 6: e12210
14 Sachdev A, Simalti A, Kumar A, Gupta N, Gupta D, Chugh P. Outcome prediction value of red cell distribution width in critically-ill children. Indian Pediatr 2018; 55 (05) 414-416
15 Ramby AL, Goodman DM, Wald EL, Weiss SL. Red blood cell distribution width as a pragmatic marker for outcome in pediatric critical illness. PLoS One 2015; 10 (06) e0129258
16 Devina T, Lubis M, Mutiara E. et al. Red cell distribution width and mortality in pediatric sepsis. Paediatr Indones 2016; 56: 320-324
17 Matehuala S, Pasala S, Goudie A. et al. Association between elevated RBC distribution width and multiple organ dysfunction in pediatric critical illness. Pediatr Crit Care Med 2020; 21 (09) e740-e746
18 Kim DH, Ha EJ, Park SJ, Jhang WK. Evaluation of the usefulness of red blood cell distribution width in critically ill pediatric patients. Medicine (Baltimore) 2020; 99 (36) e22075
19 Said AS, Spinella PC, Hartman ME. et al. Red blood cell distribution width: biomarker for red cell dysfunction and critical illness outcome?. Pediatr Crit Care Med 2017; 18 (02) 134-142
20 Gauchan E, Basnet S. High red cell distribution width as a biomarker of mortality in critically ill paediatric patients. J Nepal Paediatr Soc 2020; 15: 210-216
21 Hashemi SM, Khanbabaee G, Salarian S, Fariborzi M, Kiumarsi A. Association between red cell distribution width and mortality in pediatric patients admitted to intensive care units. Iran J Blood Cancer 2017; 9: 54-58
22 Shah N, Pahuja M, Pant S. et al. Red cell distribution width and risk of cardiovascular mortality: Insights from National Health and Nutrition Examination Survey (NHANES)-III. Int J Cardiol 2017; 232: 105-110
23 Sukewanti NM, Hartawan IN, Wati DK, Suparyatha IB, Ryalino C. Correlation of red cell distribution width and serum lactate levels in critically ill pediatric patients. Bali J Anaesthesiol 2020; 4: 104
24 Miranda SJ. Validity of red cell distribution width as a predictor of clinical outcomes in pediatric patients diagnosed with pneumonia. Chest 2017; 152: A843
25 De Domenico I, Ward DM, Kaplan J. Hepcidin regulation: ironing out the details. J Clin Invest 2007; 117 (07) 1755-1758
26 van Zeben D, Bieger R, van Wermeskerken RK, Castel A, Hermans J. Evaluation of microcytosis using serum ferritin and red blood cell distribution width. Eur J Haematol 1990; 44 (02) 106-109
27 Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics 2014; 6 (04) 748-773
28 Nangaku M, Eckardt KU. Pathogenesis of renal anemia. Semin Nephrol 2006; 26 (04) 261-268
29 Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC. Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med 2009; 133 (04) 628-632
30 Vallurupalli M, MacFadyen JG, Glynn RJ. et al. Effects of interleukin-1β inhibition on incident anemia: Exploratory analyses from a randomized trial. Ann Intern Med 2020; 172 (08) 523-532
31 Pietras EM. Inflammation: a key regulator of hematopoietic stem cell fate in health and disease. Blood 2017; 130 (15) 1693-1698
32 Li G, Jia P, Zhao J. et al. Usefulness of RBC distribution width and C-reactive protein to predict mortality in pediatric non-cardiac critical illness. Am J Emerg Med 2019; 37 (12) 2143-2150
33 Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286 (03) 327-334
34 Saleh MA, Kasem YT, Amin HH. Evaluation of neonatal sepsis and assessment of its severity by Red Cell Distribution Width indicator. Egypt J Community Med 2017; 35: 21-30
35 Cosar H, Yilmaz O, Temur M, Ozun OP, Bulut Y, Karakulak M. Relationship between early-onset neonatal sepsis and red blood cell distribution width (RDW). J Hematol Thrombo Dis 2017; 5: 266
36 Perkins SL. Examination of blood and bone marrow. In: Greer JP, Foerster J, Lukens JN. et al, eds. Wintrobe's Clinical Hematology. 11th ed. Salt Lake City, UT: Lippincott Wilkins & Williams; 2003: 5-25
37 Podhorecka M, Halicka D, Szymczyk A. et al. Assessment of red blood cell distribution width as a prognostic marker in chronic lymphocytic leukemia. Oncotarget 2016; 7 (22) 32846-32853
38 Periša V, Zibar L, Sinčić-Petričević J, Knezović A, Periša I, Barbić J. Red blood cell distribution width as a simple negative prognostic factor in patients with diffuse large B-cell lymphoma: a retrospective study. Croat Med J 2015; 56 (04) 334-343
39 Iriyama N, Hatta Y, Kobayashi S. et al. Higher red blood cell distribution width is an adverse prognostic factor in chronic-phase chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Anticancer Res 2015; 35 (10) 5473-5478
40 Buckstein R, Jang K, Friedlich J. et al. Estimating the prevalence of myelodysplastic syndromes in patients with unexplained cytopenias: a retrospective study of 322 bone marrows. Leuk Res 2009; 33 (10) 1313-1318
41 Yčas JW, Horrow JC, Horne BD. Persistent increase in red cell size distribution width after acute diseases: a biomarker of hypoxemia?. Clin Chim Acta 2015; 448: 107-117
42 Schepens T, De Dooy JJ, Verbrugghe W, Jorens PG. Red cell distribution width (RDW) as a biomarker for respiratory failure in a pediatric ICU. J Inflamm (Lond) 2017; 14: 12
43 Grant BJ, Kudalkar DP, Muti P. et al. Relation between lung function and RBC distribution width in a population-based study. Chest 2003; 124 (02) 494-500
44 Wang M, Wang W, Abeywardane A. et al. Autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: analysis of 533 adult patients who underwent transplantation at King's College Hospital. Biol Blood Marrow Transplant 2015; 21 (01) 60-66
45 Platt OS, Brambilla DJ, Rosse WF. et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med 1994; 330 (23) 1639-1644
46 Spence RK, Carson JA, Poses R. et al. Elective surgery without transfusion: influence of preoperative hemoglobin level and blood loss on mortality. Am J Surg 1990; 159 (03) 320-324

Supplementary Material

Supplementary Material