Anemia measurements to distinguish between viral and bacterial infections in the emergency department

  • Yael Steuerman
  • Asaf Wasserman
  • David Zeltser
  • Itzhak Shapira
  • Daniel Trotzky
  • Pinchas Halpern
  • Ahuva Meilik
  • Eli Raykhshtat
  • Shlomo Berliner
  • Ori Rogowski
  • Irit Gat-Viks
  • Shani Shenhar-TsarfatyEmail author
Original Article


The clinical diagnosis of acute infections in the emergency department is a challenging task due to the similarity in symptom presentation between virally and bacterially infected individuals, while the use of routine laboratory tests for pathogen identification is often time-consuming and may contain contaminants. We investigated the ability of various anemia-related parameters, including hemoglobin, red cell distribution width (RDW), and iron, to differentiate between viral and bacterial infection in a retrospective study of 3883 patients admitted to the emergency department with a confirmed viral (n = 1238) or bacterial (n = 2645) infection based on either laboratory tests or microbiological cultures. The ratio between hemoglobin to RDW was found to be significant in distinguishing between virally and bacterially infected patients and outperformed other anemia measurements. Moreover, the predictive value of the ratio was high even in patients presenting with low C-reactive protein values (< 21 mg/L). We followed the dynamics of hemoglobin, RDW, and the ratio between them up to 72 h post emergency department admission, and observed a consistent discrepancy between virally and bacterially infected patients over time. Additional analysis demonstrated higher levels of ferritin and lower levels of iron in bacterially infected compared with virally infected patients. The anemia measurements were associated with length of hospital stay, where all higher levels, except for RDW, corresponded to a shorter hospitalization period. We highlighted the importance of various anemia measurements as an additional host-biomarker to discern virally from bacterially infected patients.


Emergency department Anemia Red cell distribution width Viral infection Bacterial infection C-reactive protein 


Funding information

This work was financially supported by the Israel Science Foundation Grant 288/16 (YS and IG-V). Partial fellowships were from the European Research Council (637885), the Edmond J. Safra Center for Bioinformatics at Tel Aviv University (YS), and a Shulamit Aloni Scholarship (YS). IG-V is a Faculty Fellow of the Edmond J. Safra Center for Bioinformatics at Tel Aviv University. S.S.T and A.M were financially supported by the ELROV grant.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval and inform consent

The study was reviewed and approved by the Tel-Aviv medical center institutional Helsinki Committee (number 0491-17). Study participants gave their written informed consent for participation according to the instructions of the local ethics committee.


  1. 1.
    Robriquet L, Séjourné C, Kipnis E, D’herbomez M, Fourrier F (2013) A composite score combining procalcitonin, C-reactive protein and temperature has a high positive predictive value for the diagnosis of intensive care-acquired infections. BMC Infect Dis.
  2. 2.
    Gibot S, Béné MC, Noel R, Massin F, Guy J, Cravoisy A et al (2012) Combination biomarkers to diagnose sepsis in the critically ill patient. Am J Respir Crit Care Med.
  3. 3.
    Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin. Infect. Dis. 2004 15;39:206–17. doi:
  4. 4.
    Delèvaux I, André M, Colombier M, Albuisson E, Meylheuc F, Bègue R-J et al (2003) Can procalcitonin measurement help in differentiating between bacterial infection and other kinds of inflammatory processes? Ann Rheum Dis 62:337–340. CrossRefGoogle Scholar
  5. 5.
    Sasaki K, Fujita I, Hamasaki Y, Miyazaki S. Differentiating between bacterial and viral infection by measuring both C-reactive protein and 2′-5′-oligoadenylate synthetase as inflammatory markers. J. Infect. Chemother. 2002;doi:
  6. 6.
    Van Der Meer V, Neven AK, Van Den Broek PJ, Assendelft WJJ. Diagnostic value of C reactive protein in infections of the lower respiratory tract: systematic review. Br. Med. J. 2005;doi:
  7. 7.
    Limper M, de Kruif MD, Duits AJ, Brandjes DPM, van Gorp ECM. The diagnostic role of procalcitonin and other biomarkers in discriminating infectious from non-infectious fever. J. Infect. 2010;doi:
  8. 8.
    Kapasi AJ, Dittrich S, González IJ, Rodwell TC (2016) Host biomarkers for distinguishing bacterial from non-bacterial causes of acute febrile illness: a comprehensive review. PLoS One 11.
  9. 9.
    Nemeth E, Ganz T (2014) Anemia of inflammation. Hematol Oncol Clin North Am.
  10. 10.
    Weiss G, Ganz T, Goodnough LT (2018) Anemia of inflammation. Blood.
  11. 11.
    Viana MB (2011) Anemia and infection: a complex relationship. Rev Bras Hematol Hemoter 33:90–92. CrossRefGoogle Scholar
  12. 12.
    Ekregbesi P, Shankar-Hari M, Bottomley C, Riley EM, Mooney JP (2018) Relationship between anaemia, haemolysis, inflammation and haem oxygenase-1 at admission with sepsis: a pilot study. Sci Rep 8:11198. CrossRefGoogle Scholar
  13. 13.
    Ku NS, Kim HW, Oh HJ, Kim YC, Kim MH, Song JE et al (2012) Red blood cell distribution width is an independent predictor of mortality in patients with Gram-negative bacteremia. Shock.
  14. 14.
    Lippi G, Targher G, Montagnana M, Salvagno GL, Zoppini G, Guidi GC (2009) Relation between red blood cell distribution width and inflammatory biomarkers in a large cohort of unselected outpatients. Arch Pathol Lab Med.
  15. 15.
    Jansma G, De Lange F, Kingma P, Ar Vellinga N, Koopmans M, Kuiper MA et al (2015) ‘Sepsis-related anemia’ is absent at hospital presentation; a retrospective cohort analysis. BMC Anesthesiol.
  16. 16.
    Fuad Muady G, Bitterman H, Laor A, Vardi M, Urin V, Ghanem-Zoubi N (2016) Hemoglobin levels and blood transfusion in patients with sepsis in Internal Medicine Departments. BMC Infect Dis.
  17. 17.
    Piagnerelli M, Boudjeltia KZ, Gulbis B, Vanhaeverbeek M, Vincent J-L (2007) Anemia in sepsis: the importance of red blood cell membrane changes. Transfus Altern Transfus Med 9:143–149. CrossRefGoogle Scholar
  18. 18.
    Walsh TS, Saleh E-E-D (2006) Anaemia during critical illness. Br J Anaesth 97:278–291. CrossRefGoogle Scholar
  19. 19.
    Sadaka F, O’Brien J, Prakash S (2013) Red cell distribution width and outcome in patients with septic shock. J Intensive Care Med 28:307–313. CrossRefGoogle Scholar
  20. 20.
    Jo YH, Kim K, Lee JH, Kang C, Kim T, Park H-M et al (2013) Red cell distribution width is a prognostic factor in severe sepsis and septic shock. Am J Emerg Med 31:545–548. CrossRefGoogle Scholar
  21. 21.
    Bazick HS, Chang D, Mahadevappa K, Gibbons FK, Christopher KB (2011) Red cell distribution width and all-cause mortality in critically ill patients. Crit Care Med 39:1913–1921. CrossRefGoogle Scholar
  22. 22.
    Wang F, Pan W, Pan S, Ge J, Wang S, Chen M (2011) Red cell distribution width as a novel predictor of mortality in ICU patients. Ann. Med 43:40–46. CrossRefGoogle Scholar
  23. 23.
    Mahmood NA, Mathew J, Kang B, DeBari VA, Khan MA (2014) Broadening of the red blood cell distribution width is associated with increased severity of illness in patients with sepsis. Int J Crit Illn Inj Sci 4:278–282. CrossRefGoogle Scholar
  24. 24.
    Sun P, Zhang F, Chen C, et al (2016) The ratio of hemoglobin to red cell distribution width as a novel prognostic parameter in esophageal squamous cell carcinoma: a retrospective study from southern China. Oncotarget 7(27):42650–42660. 
  25. 25.
    Kernan KF, Carcillo JA (2017) Hyperferritinemia and inflammation. Int Immunol.
  26. 26.
    Kossiva L, Gourgiotis DI, Tsentidis C, Anastasiou T, Marmarinos A, Vasilenko H et al (2012) Serum hepcidin and ferritin to iron ratio in evaluation of bacterial versus viral infections in children: a single-center study. Pediatr Infect Dis J 31:795–798. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yael Steuerman
    • 1
  • Asaf Wasserman
    • 2
  • David Zeltser
    • 2
  • Itzhak Shapira
    • 2
  • Daniel Trotzky
    • 3
  • Pinchas Halpern
    • 3
  • Ahuva Meilik
    • 4
  • Eli Raykhshtat
    • 4
  • Shlomo Berliner
    • 2
  • Ori Rogowski
    • 2
  • Irit Gat-Viks
    • 1
  • Shani Shenhar-Tsarfaty
    • 2
    Email author
  1. 1.School of Molecular Cell Biology and Biotechnology, Department of Cell Research and Immunology, George S. Wise Faculty of Life SciencesTel Aviv UniversityTel AvivIsrael
  2. 2.Department of Internal Medicine “C”, “D” and “E”, Tel Aviv Sourasky Medical Center and Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Department of Emergency Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Affiliated to the Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  4. 4.Clinical Performances Research and Operational Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Affiliated to the Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

Personalised recommendations