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Diagnostic performance of morphological analysis and red blood cell parameter-based algorithms in the routine laboratory screening of heterozygous haemoglobinopathies

  • Germain Simon ORCID logo EMAIL logo , François Boemer ORCID logo , Géraldine Luis ORCID logo , André Gothot ORCID logo , Françoise Tassin and Aurore Keutgens ORCID logo
Published/Copyright: May 22, 2025
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 9

Abstract

Objectives

The aim of this study was to carry out a cross-analysis of the morphological abnormalities (MA) and the electrophoretic profile (EP) of blood samples suspect for heterozygous haemoglobinopathies (HTZ HGP). Screening for HTZ HGP was based on erythrocyte parameters provided by the Sysmex XN analysers.

Methods

A total of 596,000 blood samples was included in the study. According to the results of the mean corpuscular haemoglobin concentration (MCHC), the percentage of microcytes (Micro%) and the standard deviation of the red blood cell distribution width (RDW-SD), 842 different adults were screened as suspect for HTZ HGP and underwent simultaneous morphological analysis of red blood cells (RBCMA) and haemoglobin fraction analysis.

Results

The majority (72.8 %) of HTZ HGP suspects presented a pathological EP, mostly compatible with a confirmed β-thalassaemia trait (50.1 %) or a heterozygous β-haemoglobin variant (12.2 %). MA were identified in 360 (42.8 %) samples and 70 (8.3 %) of these had 3 or more MA. The most common MA was poikilocytosis (28.1 %). Patients with at least 1 MA detected were more likely to have a pathological EP (p=0.003). However, correlation between the number of MA detected and the type of EP was negligible.

Conclusions

Screening for HTZ HGP based on erythrocyte parameters measured on Sysmex XN analysers is a relevant tool with a positive predictive value of 72.8 % and definitely superior to microscopic RBCMA which now appears to be of low added value and obsolete in this indication.

Keywords: haemoglobin electrophoresis; haemoglobinopathy screening; red blood cell morphology; red blood cell parameter; Sysmex XN; thalassaemia
Corresponding author: Germain Simon, MD, Department of Laboratory Hematology, University Hospital Center of Liège, Avenue de l’Hôpital 1, 4000 Liège, Belgium, E-mail:

  1. Research ethics: The local Institutional Review Board deemed the study exempt from review.

  2. Informed consent: Not applicable.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0210).

Received: 2025-02-21
Accepted: 2025-04-30
Published Online: 2025-05-22
Published in Print: 2025-08-26

© 2025 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2025-0210
Keywords for this article
haemoglobin electrophoresis; haemoglobinopathy screening; red blood cell morphology; red blood cell parameter; Sysmex XN; thalassaemia

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Macroprolactinaemia – some progress but still an ongoing problem
  4. Review
  5. Understanding the circulating forms of cardiac troponin: insights for clinical practice
  6. Opinion Papers
  7. New insights in preanalytical quality
  8. IFCC recommendations for internal quality control practice: a missed opportunity
  9. Genetics and Molecular Diagnostics
  10. Evaluation of error detection and treatment recommendations in nucleic acid test reports using ChatGPT models
  11. General Clinical Chemistry and Laboratory Medicine
  12. Pre-analytical phase errors constitute the vast majority of errors in clinical laboratory testing
  13. Improving the efficiency of quality control in clinical laboratory with an integrated PBRTQC system based on patient risk
  14. IgA-type macroprolactin among 130 patients with macroprolactinemia
  15. Prevalence and re-evaluation of macroprolactinemia in hyperprolactinemic patients: a retrospective study in the Turkish population
  16. Defining dried blood spot diameter: implications for measurement and specimen rejection rates
  17. Screening primary aldosteronism by plasma aldosterone-to-angiotensin II ratio
  18. Assessment of serum free light chain measurements in a large Chinese chronic kidney disease cohort: a multicenter real-world study
  19. Beyond the Hydrashift assay: the utility of isoelectric focusing for therapeutic antibody and paraprotein detection
  20. Direct screening and quantification of monoclonal immunoglobulins in serum using MALDI-TOF mass spectrometry without antibody enrichment
  21. Effect of long-term frozen storage on stability of kappa free light chain index
  22. Impact of renal function impairment on kappa free light chain index
  23. Standardization challenges in antipsychotic drug monitoring: insights from a national survey in Chinese TDM practices
  24. Potential coeliac disease in children: a single-center experience
  25. Vitamin D metabolome in preterm infants: insights into postnatal metabolism
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  27. Development of commutable candidate certified reference materials from protein solutions: concept and application to human insulin
  28. Reference Values and Biological Variations
  29. Biological variation of serum cholinesterase activity in healthy subjects
  30. Hematology and Coagulation
  31. Diagnostic performance of morphological analysis and red blood cell parameter-based algorithms in the routine laboratory screening of heterozygous haemoglobinopathies
  32. Cancer Diagnostics
  33. Promising protein biomarkers for early gastric cancer: clinical performance of combined detection
  34. Infectious Diseases
  35. The accuracy of presepsin in diagnosing neonatal late-onset sepsis in critically ill neonates: a prospective study
  36. Corrigendum
  37. The Unholy Grail of cancer screening: or is it just about the Benjamins?
  38. Letters to the Editor
  39. Analytical validation of hemolysis detection on GEM Premier 7000
  40. Reconciling reference ranges and clinical decision limits: the case of thyroid stimulating hormone
  41. Contradictory definitions give rise to demands for a right to unambiguous definitions
  42. Biomarkers to measure the need and the effectiveness of therapeutic supplementation: a critical issue
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