Home Medicine Red cell indices: differentiation between β-thalassemia trait and iron deficiency anemia and application to sickle cell disease and sickle cell thalassemia
Article
Licensed
Unlicensed Requires Authentication

Red cell indices: differentiation between β-thalassemia trait and iron deficiency anemia and application to sickle cell disease and sickle cell thalassemia

  • Chaima A. Sahli , Amina Bibi EMAIL logo , Faida Ouali , Sondess Hadj Fredj , Boutheina Dakhlaoui , Rym Othmani , Naouel Laaouini , Latifa Jouini , Fekria Ouenniche , Hajer Siala , Imed Touhami , Mariem Becher , Slaheddine Fattoum , Nour El Houda Toumi and Taieb Messaoud
Published/Copyright: March 13, 2013
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 51 Issue 8

Abstract

Background: In Tunisia, thalassemia and sickle cell disease (SS) represent the most prevalent monogenic hemoglobin disorders with 2.21% and 1.89% of carriers, respectively. This study aims to evaluate the diagnosis reliability of 12 red blood cell (RBC) indices in differentiation of β-thalassemia trait (β-TT) from iron deficiency anemia (IDA) and between homozygous SS and sickle cell thalassemia (ST).

Methods: The study covered 384 patients divided into three groups. The first one is composed of 145 control group, the second consists of 57 β-TT and 52 IDA subjects and the last one with 88 SS and 42 ST patients. We calculated sensitivity, specificity, positive-predictive values, negative-predictive values, percentage of correctly identified patients and Youden’s Index (YI) for each indice. We also established new cut-off values by receiver operating characteristic curves for each indice. An evaluation study was performed on another population composed of 106 β-TT, 125 IDA, 31 SS, and 17 ST patients.

Results: Srivastava Index (SI) shows the highest reliability in discriminating β-TT from IDA at 5.17 as a cut-off and also SS from ST with 7.7 as another threshold. Mentzer Index (MI) and RBC appear also useful in both groups with new cut-offs slightly different from those described in literature for β-TT and IDA.

Conclusions: The effectiveness and the simplicity of calculation of these indices make them acceptable and easy to use. They can be relied on for differential diagnosis and even for diagnosis of β-TT with atypical HbA2 levels.

Keywords: β-thalassemia trait; discrimination indice; iron deficiency anemia; sickle cell disease; sickle cell thalassemia
Corresponding author: Amina Bibi, MD, Biochemistry Laboratory, Children’s Hospital, Bab Saadoun Square, Tunis, Tunisia, Phone: +216 71 578450, Fax: +216 71 566463

This work received support from the Ministry of Scientific Research and Technology and Competence Development (LR00SP03).

The authors are grateful to Mrs. Angela Gudgin (Manchester, UK) and Mr. Mourad Bouatay (Tunis, Tunisia), for their contribution in checking the manuscript language.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. Fattoum S. Evolution of hemoglobinopathy in Africa: results, problems and prospect. Medit J Hemat Infect Dis 2009;1:e2009005.10.4084/MJHID.2009.005Search in Google Scholar

2. Nobili B, Silverio P, Rosaria Matarese SM, Conte ML, Miraglia del Giudice E. Evaluation of body iron status in Italian carriers of beta-thalassemia trait. Nutr Res 2001;21:55–6.10.1016/S0271-5317(00)00295-5Search in Google Scholar

3. Bibi A, Benmoussa S, Torjman A, Taboubi N, Ouali F, Cherif H, etal. Intérêt de la dissociation albumine-transferrine (dat) dans le diagnostic de la carence martiale dans une cohorte de 1288 écoliers dans une région du grand Tunis. Ann Biol Clin 2006;64:1–9.Search in Google Scholar

4. Mentzer WC Jr. Differentiation of iron deficiency from thalassemia trait. Lancet 1973;i:882.10.1016/S0140-6736(73)91446-3Search in Google Scholar

5. Green R, King R. A new red blood cell discriminant incorporating volume dispersion for differentiating iron deficiency anemia from thalassemia minor. Blood Cells 1989;15:481–95.Search in Google Scholar PubMed

6. Jayabose S, Giavanelli J, Levendoglu-Tugal O, Sandoval C, Ozkaynak F, Visintainer P. Differentiating iron deficiency anemia from Thalassemia minor by using an RDW-based index. J Pediatr Hematol 1999;21:314.10.1097/00043426-199907000-00040Search in Google Scholar

7. England JM, Fraser PM. Differentiation of iron deficiency from thalassemia trait by routine blood count. Lancet 1973;1:449–52.10.1016/S0140-6736(73)91878-3Search in Google Scholar PubMed

8. Shine L, Lal S. A strategy to detect beta-thalassemia minor. Lancet 1977;1:692–4.10.1016/S0140-6736(77)92128-6Search in Google Scholar PubMed

9. Srivastava PC. Differentiation of thalassemia minor from iron deficiency. Lancet 1973;ii:154–5.10.1016/S0140-6736(73)93104-8Search in Google Scholar

10. Ricerca BM, Stortis S, d’Onofrio G, Mancini S, Vittori M, Campisi S, etal. Differentiation of iron deficiency from thalassemia trait: a new approach. Haematologica 1987;72:409–13.Search in Google Scholar

11. Ehsani M, Darvish A, Aslani A, Seighali F. A new formula for differentiation if iron deficiency anemia (IDA) and thalassemia trait (TT). Turk J Hematol 2005;22:268.Search in Google Scholar

12. Sirdah MI, Tarazi E, Al Najjar E, Al Haddad R. Evaluation of the diagnostic reliability of different RBC indices and formulas in the differentiation of the β-thalassemia minor from iron deficiency in Palestinian population. Int J Lab Hematol 2008;30:324–30.10.1111/j.1751-553X.2007.00966.xhttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000257716900010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

13. Huber AR, Ottiger C, Risch L, Regenass S, Hergersberg M, Herklotz R. Thalassemie-syndrome: klinik und diagnose. Syndromes thalassémiques: Clinique et diagnostic. Schweiz Med Forum 2004;4:947–52.10.4414/fms.2004.05311Search in Google Scholar

14. Klee GG, Fairbanks VF, Pierre RV, O’Sullivan MB. Routine erythrocyte measurements in diagnosis of iron deficiency anemia and thalassemia minor. Am J Clin Pathol 1976;66: 870–7.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000316369100016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

15. Marti HR, Fisher S, Killer D, Bürgi W. Can automated haematology analysers discriminate thalassemia from iron deficiency? Acta Haematol 1987;78:180–3.10.1159/000205871Search in Google Scholar PubMed

16. Poncz M, Solowiejczyk D, Harpel B, Mory Y, Schwartz E, Surrey S. Construction of human gene libraries from small amounts of peripheral blood: analysis of β-like globin genes. Hemoglobin 1982;6:27–33.10.3109/03630268208996930Search in Google Scholar PubMed

17. Maggio A, Giambona A, Cai SP, Wall J, Kan YW, Chehab FF. Rapid and simultaneous typing of hemoglobin S, hemoglobin C and seven Mediterranean β -thalassemia mutations by covalent reverse dot blot analysis: application to prenatal diagnosis in Sicily. Blood 1993;81:239–42.10.1182/blood.V81.1.239.239Search in Google Scholar PubMed

18. Old JM, Khan SN, Verma I, Fucharoen S, Kleanthous M, Loannou P, etal. A multi-center study in order to further define the molecular basis of β -thalassemia in Thailand, Pakistan, Sri Lanka, Mauritius, Syria, and India, and to develop a simple molecular diagnostic strategy by amplification refractory mutation system-polymerase chain reaction. Hemoglobin 2001;25:397–407.10.1081/HEM-100107877Search in Google Scholar

19. Fattoum S, Messaoud T, Bibi. A molecular basis of beta-thalassemia in the population of Tunisia. Hemoglobin 2004;28:177–87.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000284221000004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1081/HEM-120040307Search in Google Scholar PubMed

20. Bibi A, Messaoud T, Beldjord C, Fattoum S. Detection of two rare β-thalassemia alleles found in the Tunisian population: codon 47 (+A) and codons 106/107 (+G). Hemoglobin 2006;30: 437–47.10.1080/03630260600867933Search in Google Scholar

21. Bessman JD, Feinstein DI. Quantitative anisocytosis as a discriminant between iron deficiency and thalassemia minor. Blood 1979;53:288–93.10.1182/blood.V53.2.288.288Search in Google Scholar PubMed

22. England JM, Fraser P. Discrimination between iron deficiency and heterozygous-thalassaemia syndromes in differential diagnosis of microcytosis. Lancet 1979;i:145–8.10.1016/S0140-6736(79)90532-4Search in Google Scholar

23. Ntaios GA, Chatzinikolaou A, Saouli Z, Girtovitis F, Tsapanidou M, Kaiafa G, etal. Discrimination indices as screening tests for beta-thalassemia trait. Ann Hematol 2007;86:487–91.10.1007/s00277-007-0302-xSearch in Google Scholar PubMed

24. Ehsani M, Shahgholi E, Rahiminejad M, Seighali F, Rashidi A. A new index for discrimination between iron deficiency anemia and beta-thalassemia trait minor: results in 284 patients. Pak J Biol Sci 2009;12:473–5.10.3923/pjbs.2009.473.475Search in Google Scholar PubMed

25. Urrechaga E, Borque L, Escanero JF. The role of automated measurement of RBC subpopulations in differential diagnosis of microcytic anemia and β -thalassemia screening. Am J Clin Pathol 2011;135:374–9.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000287718200005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1309/AJCPJRH1I0XTNFGASearch in Google Scholar PubMed

26. Alfadhli S, Alawadhi A, Alkhaldi D. Validity assessment of nine discriminant functions used for the differentiation between iron deficiency anemia and thalassemia minor. J Trop Pediatr 2006;53:93–7.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000245511700006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1093/tropej/fml070Search in Google Scholar PubMed

27. Janel A, Roszky L, Rapatel C, Mareynat G, Berger MG, Serre-Sapin AF. Proposal of a score combining red blood cell indices for early differentiation of beta-thalassemia minor from iron deficiency anemia. Hematology 2011;16:123–7.10.1179/102453311X12940641877849http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000288594400011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

28. Okan V, Cigiloglu A, Cifci S, Yilmaz M, Pehlivan M. Red cell indices and functions differentiating patients with the β-thalassemia trait from those with iron deficiency anemia. J Int Med Res 2009;37:25–30.10.1177/147323000903700103http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000264163500003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

29. Shen C, Jianq YM, Shi H, Liu JH, Zhou WJ, Dai QK, etal. Evaluation of indices in differentiation between iron deficiency anemia and β-thalassemia trait for Chinese children. J Pediatr Hematol Oncol 2010;32:218–22.10.1097/MPH.0b013e3181e5e26ehttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000280666100022&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

30. Huisman TH, Carver MF. The β- and δ-thalassemia repository (9th ed., part I). Hemoglobin 1998;22:169–95.10.3109/03630269809092143Search in Google Scholar PubMed

31. Sahli CA, Bibi A, Ouali F, Siala Hajer, Hadj Fredj S, Othmeni R, etal. δ0-thalassemia in cis of βKnossos globin gene: first homozygous description in Thalassemia Intermedia Libyans and first combination with Codon 39 in Thalassemia Intermedia Tunisian patient. Clin Chem Lab Med 2012;50:1743–8.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000309955500008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1515/cclm-2012-0102Search in Google Scholar PubMed

32. Giambona A, Passarello C, Vinciguerra M, Li Muli R, Teresi P, Anzà M, etal. Significance of borderline hemoglobin A2 values in an Italian population with a high prevalence of β-thalassemia. Haematologica 2008;93:1380–4.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000259120100017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.3324/haematol.12840Search in Google Scholar PubMed

33. Demir A, Yarali N, Fisgin T, Duru F, Kara A. Most reliable indices in differentiation between thalassemia trait and iron deficiency anemia. Pediatr Int 2002;44:612–6.10.1046/j.1442-200X.2002.01636.xSearch in Google Scholar PubMed

Received: 2012-12-02
Accepted: 2013-02-08
Published Online: 2013-03-13
Published in Print: 2013-08-01

©2013 by Walter de Gruyter Berlin Boston

Articles in the same Issue

  1. Letters to the Editors
  2. Clinical utility of serum tumor markers and cytokines in cervical cancer and neoplasia
  3. Establishing reference intervals for LDL subfractions in a Korean population using the Lipoprint LDL system
  4. Measurement imprecision of common urinary biochemical analytes on the Roche Cobas 6000 system
  5. A comparison between turbidimetric inhibition immunoassay and capillary electrophoresis in glycated hemoglobin (HbA1c) measurement
  6. Commutability: a peculiar property of calibration and control materials. Definition and evaluation
  7. Diagnostic sensitivity of a panel of tests to detect monoclonal protein in Korean multiple myeloma patients
  8. Commutability of proficiency testing (PT): status of the matrix-related bias in general clinical chemistry
  9. Masthead
  10. Masthead
  11. Editorial
  12. Why specifications for allowable glucose meter errors should include 100% of the data
  13. Reviews
  14. ABO blood group: old dogma, new perspectives
  15. Trace elements and bone health
  16. Mini Review
  17. The role of transcription factors in laboratory medicine
  18. Opinion Papers
  19. Nobelitis: a common disease among Nobel laureates?
  20. The syndrome of the “obsessive-compulsory scientist”: a new mental disorder?
  21. Can current analytical quality performance of UK clinical laboratories support evidence-based guidelines for diabetes and ischaemic heart disease? – A pilot study and a proposal
  22. Guidelines and Recommendations
  23. Survey of national guidelines, education and training on phlebotomy in 28 European countries: an original report by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PA)
  24. General Clinical Chemistry and Laboratory Medicine
  25. Red cell indices: differentiation between β-thalassemia trait and iron deficiency anemia and application to sickle cell disease and sickle cell thalassemia
  26. Problems in determining thalassemia carrier status in a program for prevention and control of severe thalassemia syndromes: a lesson from Thailand
  27. An enzyme linked immunosorbent assay (ELISA) for the determination of the human haptoglobin phenotype
  28. Blood loss from laboratory diagnostic tests in children
  29. Hematocrit correction does not improve glucose monitor accuracy in the assessment of neonatal hypoglycemia
  30. Evaluation of a mobile clinical pathology laboratory developed for the home care of pediatric patients following transplantation of peripheral blood precursor cells
  31. Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism
  32. Influence of spurious hemolysis on blood gas analysis
  33. Serum procalcitonin predicts development of acute kidney injury in patients with suspected infection
  34. Reference Values and Biological Variations
  35. Nationwide multicenter study aimed at the establishment of common reference intervals for standardized clinical laboratory tests in Japan
  36. Cancer Diagnostics
  37. Application of BRAF, NRAS, KRAS mutations as markers for the detection of papillary thyroid cancer from FNAB specimens by pyrosequencing analysis
  38. Comparative evaluation of the My5-FU™ immunoassay and LC-MS/MS in monitoring the 5-fluorouracil plasma levels in cancer patients
https://doi.org/10.1515/cclm-2012-0842
Keywords for this article
β-thalassemia trait; discrimination indice; iron deficiency anemia; sickle cell disease; sickle cell thalassemia

Articles in the same Issue

  1. Letters to the Editors
  2. Clinical utility of serum tumor markers and cytokines in cervical cancer and neoplasia
  3. Establishing reference intervals for LDL subfractions in a Korean population using the Lipoprint LDL system
  4. Measurement imprecision of common urinary biochemical analytes on the Roche Cobas 6000 system
  5. A comparison between turbidimetric inhibition immunoassay and capillary electrophoresis in glycated hemoglobin (HbA1c) measurement
  6. Commutability: a peculiar property of calibration and control materials. Definition and evaluation
  7. Diagnostic sensitivity of a panel of tests to detect monoclonal protein in Korean multiple myeloma patients
  8. Commutability of proficiency testing (PT): status of the matrix-related bias in general clinical chemistry
  9. Masthead
  10. Masthead
  11. Editorial
  12. Why specifications for allowable glucose meter errors should include 100% of the data
  13. Reviews
  14. ABO blood group: old dogma, new perspectives
  15. Trace elements and bone health
  16. Mini Review
  17. The role of transcription factors in laboratory medicine
  18. Opinion Papers
  19. Nobelitis: a common disease among Nobel laureates?
  20. The syndrome of the “obsessive-compulsory scientist”: a new mental disorder?
  21. Can current analytical quality performance of UK clinical laboratories support evidence-based guidelines for diabetes and ischaemic heart disease? – A pilot study and a proposal
  22. Guidelines and Recommendations
  23. Survey of national guidelines, education and training on phlebotomy in 28 European countries: an original report by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) working group for the preanalytical phase (WG-PA)
  24. General Clinical Chemistry and Laboratory Medicine
  25. Red cell indices: differentiation between β-thalassemia trait and iron deficiency anemia and application to sickle cell disease and sickle cell thalassemia
  26. Problems in determining thalassemia carrier status in a program for prevention and control of severe thalassemia syndromes: a lesson from Thailand
  27. An enzyme linked immunosorbent assay (ELISA) for the determination of the human haptoglobin phenotype
  28. Blood loss from laboratory diagnostic tests in children
  29. Hematocrit correction does not improve glucose monitor accuracy in the assessment of neonatal hypoglycemia
  30. Evaluation of a mobile clinical pathology laboratory developed for the home care of pediatric patients following transplantation of peripheral blood precursor cells
  31. Folic acid supplementation does not reduce intracellular homocysteine, and may disturb intracellular one-carbon metabolism
  32. Influence of spurious hemolysis on blood gas analysis
  33. Serum procalcitonin predicts development of acute kidney injury in patients with suspected infection
  34. Reference Values and Biological Variations
  35. Nationwide multicenter study aimed at the establishment of common reference intervals for standardized clinical laboratory tests in Japan
  36. Cancer Diagnostics
  37. Application of BRAF, NRAS, KRAS mutations as markers for the detection of papillary thyroid cancer from FNAB specimens by pyrosequencing analysis
  38. Comparative evaluation of the My5-FU™ immunoassay and LC-MS/MS in monitoring the 5-fluorouracil plasma levels in cancer patients
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2026 De Gruyter Brill
Downloaded on 25.1.2026 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2012-0842/html
Scroll to top button