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

  • Chaima Abdelhafidh Sahli , Amina Bibi EMAIL logo , Faida Ouali , Sondess Hadj Fredj , Boutheina Dakhlaoui , Rym Othmani , Naouel Laouini , Latifa Jouini , Fekria Ouenniche , Hajer Siala , Imed Touhami , Mariem Becher , Slaheddine Fattoum , Nour El Houda Toumi and Taieb Messaoud
Published/Copyright: June 26, 2013
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 51 Issue 11

Abstract

Background: In Tunisia, thalassemia and sickle cell disease 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 a series of red blood cell indices and parameters in differentiation of beta-thalassemia trait (β-TT) from iron deficiency anemia (IDA) and between homozygous sickle cell disease (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 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, mean corpuscular hemoglobin, red blood cell, Mentzer Index (MI) and mean corpuscular hemoglobin concentration show the highest reliability in discriminating β-TT from IDA with new cut-offs slightly different from those described in literature. Ehsani Index, mean corpuscular volume, MI, Shine and Lal Index and Sirdah Index are the most powerful in the differentiation between SS and ST.

Conclusions: The effectiveness and the simplicity of calculation of these indices make them acceptable and easy to use for differential diagnosis.

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 98 414607, Fax: +216 71 566463, E-mail:

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 support played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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 2009:1.10.4084/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, et al. 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;1:882.10.1016/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;2:154–5.10.1016/S0140-6736(73)93104-8Search in Google Scholar PubMed

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

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. Thalassemie-syndrome: klinik und diagnose. Schweiz Med Forum 2004;4:947–52.10.4414/smf.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, et al. 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 PubMed

19. Fattoum S, Messaoud T, Bibi A. 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 PubMed

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;1:145–8.10.1016/S0140-6736(79)90532-4Search in Google Scholar PubMed

23. Ntaios GA, Chatzinikolaou A, Saouli Z, Girtovitis F, Tsapanidou M, Kaiafa G, et al. 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 Tropical 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. 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, et al. 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, Hajer S, Hadj Fredj S, Othmeni R, et al. 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=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed

32. Giambona A, Passarello C, Vinciguerra M, Li Muli R, Teresi P, Anzà M, et al. 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: 2013-05-13
Accepted: 2013-05-26
Published Online: 2013-06-26
Published in Print: 2013-11-01

©2013 by Walter de Gruyter Berlin Boston

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https://doi.org/10.1515/cclm-2013-0354
Keywords for this article
β-thalassemia trait; discrimination indice; iron deficiency anemia; sickle cell disease; sickle cell-thalassemia

Articles in the same Issue

  1. Letter to the Editor
  2. Elevated level of cell-free plasma DNA is associated with advanced-stage breast cancer and metastasis
  3. Is procalcitonin a reliable marker of sepsis in critically ill septic patients undergoing continuous veno-venous hemodiafiltration with “high cut-off” membranes (HCO-CVVHDF)?
  4. Challenging our serological algorithm for celiac disease (CD) diagnosis by the ESPGHAN guidelines
  5. Preanalytical quality control in a university hospital in China
  6. Racial differences and relationships between gestational thyrotropin and free thyroxine in a multiracial Asian population
  7. Analytical performance and method comparison study of the total homocysteine immunoassay on the AIA 600II analyser
  8. Easy verification of clinical chemistry reference intervals
  9. The Elecsys® Vitamin B12 assay is not affected by anti-intrinsic factor antibodies
  10. Chemiluminescence-based cobalamin assay errors: background and perspectives
  11. Congress Abstracts
  12. Abstracts IV Italian Great Network Congress Rome, 14th–18th October 2013*)
  13. Masthead
  14. Masthead
  15. Editorial
  16. Making colorectal cancer screening FITTER for purpose with quantitative faecal immunochemical tests for haemoglobin (FIT)
  17. From “panic” to “critical” values: which path toward harmonization?
  18. Review
  19. Cerebrospinal fluid analyses for the diagnosis of subarachnoid haemorrhage and experience from a Swedish study. What method is preferable when diagnosing a subarachnoid haemorrhage?
  20. Opinion Paper
  21. False myths and legends in laboratory diagnostics
  22. General Clinical Chemistry and Laboratory Medicine
  23. National survey on critical values notification of 599 institutions in China
  24. Influence of physical properties of cuvette surface on measurement of serum lipase
  25. Red cell indices: differentiation between β-thalassemia trait and iron deficiency anemia and application to sickle-cell disease and sickle-cell thalassemia
  26. Measurement of immature platelets with Abbott CD-Sapphire and Sysmex XE-5000 in haematology and oncology patients
  27. Performance characteristics of consensus approaches for small and minor paroxysmal nocturnal hemoglobinuria clone determination by flow cytometry
  28. Comparison of PR3-ANCA specific assay performance for the diagnosis of granulomatosis with polyangiitis (Wegener’s)
  29. The integration of the detection of systemic sclerosis-associated antibodies in a routine laboratory setting: comparison of different strategies
  30. Reference Values and Biological Variations
  31. Reference interval studies: what is the maximum number of samples recommended?
  32. Short-term estimation and application of biological variation of small dense low-density lipoproteins in healthy individuals
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  34. Diagnostic inconsistency of faecal immunochemical tests for haemoglobin in population screening of colorectal cancer
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