Diagnostic performance of morphological analysis and red blood cell parameter-based algorithms in the routine laboratory screening of heterozygous haemoglobinopathies. - 2025
Diagnostic performance of morphological analysis and red blood cell parameter-based algorithms in the routine laboratory screening of heterozygous haemoglobinopathies.
[en] [en] 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.
Disciplines :
Hematology
Author, co-author :
Simon, Germain ; Centre Hospitalier Universitaire de Liège - CHU > > Pool assistant - biologie clinique
Boemer, François ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale
LUIS, Géraldine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Gothot, André ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la coagulation et de l'hémostase
Tassin, Françoise ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Keutgens, Aurore ; Université de Liège - ULiège > Département des sciences cliniques
Language :
English
Title :
Diagnostic performance of morphological analysis and red blood cell parameter-based algorithms in the routine laboratory screening of heterozygous haemoglobinopathies.
Harteveld CL, Achour A, Arkesteijn SJ, Ter Huurne J, Verschuren M, Bhagwandien-Bisoen S, et al. The hemoglobinopathies, molecular disease mechanisms and diagnostics. Int J Lab Hematol 2022; 44:28-36.
Giardine B, Borg J, Viennas E, Pavlidis C, Moradkhani K, Joly P, et al. Updates of the HbVar database of human hemoglobin variants and thalassemia mutations. Nucleic Acids Res 2014; 42:1063-9.
Traeger-Synodinos J, Harteveld CL, Old JM, Petrou M, Galanello R, Giordano P, et al. EMQN Best practice guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies. Eur J Hum Genet 2015; 23:426-37.
Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008; 86: 480-7.
Lippi G, Mattiuzzi C. Updated worldwide epidemiology of inherited erythrocyte disorders. Acta Haematol 2020; 143:196-203.
GBD Sickle Cell Disease Collaborators. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000-2021: a systematic analysis from the global burden of disease study 2021. Lancet Haematol 2023; 10:585-99.
Tuo Y, Li Y, Li Y, Ma J, Yang X, Wu S, et al. Global, regional, and national burden of thalassemia, 1990-2021: a systematic analysis for the global burden of disease study 2021. eClinicalMedicine 2024; 72:102619.
Modell B, Darlison M, Birgens H, Cario H, Faustino P, Giordano PC, et al. Epidemiology of haemoglobin disorders in Europe: an overview. Scand J Clin Lab Invest 2007; 67:39-69.
Kattamis A, Forni GL, Aydinok Y, Viprakasit V. Changing patterns in the epidemiology of beta-thalassemia. Eur J Haematol 2020; 105:692-703.
Piel FB, Tatem AJ, Huang Z, Gupta S, Williams TN, Weatherall DJ. Global migration and the changing distribution of sickle haemoglobin: a quantitative study of temporal trends between 1960 and 2000. Lancet Global Health 2014; 2:80-9.
Piel FB. The present and future global burden of the inherited disorders of hemoglobin. Hematol Oncol Clin North Am 2016; 30:327-41.
Old JM. Prevention and diagnosis of haemoglobinopathies [Online]. Nicosia, Cyprus: Thalassaemia International Federation (TIF); 2019. https://thalassaemia.org.cy/wp-content/uploads/2019/11/Preventiondiagnosis-of-Hbpathies_BOOKLETNEW-1.pdf [Accessed 14 Nov 2024].
Barnes PW, McFadden SL, Machin SJ, Simson E, International Consensus Group for Hematology. The international consensus group for hematology review: suggested criteria for action following automated CBC and WBC differential analysis. Lab Hematol 2005; 11: 83-90.
Geneviève F, Galoisy AC, Mercier-Bataille D, Wagner-Ballon O, Trimoreau F, Fenneteau O, et al. Revue microscopique du frottis sanguin: propositions du Groupe Francophone d'Hematologie Cellulaire (GFHC). Rev Biol Med 2014; 55:7-16.
Palmer L, Briggs C, McFadden S, Zini G, Burthem J, Rozenberg G, et al. ICSH recommendations for the standardization of nomenclature and grading of peripheral blood cell morphological features. Int J Lab Hematol 2015; 37:287-303.
Nivaggioni V, Bouriche L, Coito S, Le Floch AS, Ibrahim-Kosta M, Leonnet C, et al. Use of Sysmex XN-10 red blood cell parameters for screening of hereditary red blood cell diseases and iron deficiency anaemia. Int J Lab Hematol 2020; 42:697-704.
Boemer F, Ketelslegers O, Minon JM, Bours V, Schoos R. Newborn screening for sickle cell disease using tandem mass spectrometry. Clin Chem 2008; 54:2036-41.
Boemer F, Cornet Y, Libioulle C, Segers K, Bours V, Schoos R. 3-years experience review of neonatal screening for hemoglobin disorders using tandem mass spectrometry. Clin Chim Acta 2011; 412:1476-9.
UK Government. SCT screening handbook for antenatal laboratories [Online]. https://www.gov.uk/government/publications/sctscreening-handbook-for-antenatal-laboratories [Accessed 14 Nov 2024].
Aguilar-Martinez P, Badens C, Bonello-Palot N, Cadet E, Couque N, Ducrocq R, et al. Flowcharts for the diagnosis and the molecular characterization of hemoglobinopathies. Ann Biol Clin 2010; 68:455-64.
Weatherall D, Clegg J, editors. The thalassaemia syndromes, 4th ed. Oxford, UK: Blackwell Science Ltd; 2001:846 p.
World Helath Organization (WHO). Serum ferritin concentrations for the assessment of iron status in individuals and populations: technical brief. Geneva, Switzerland: World Health Organization; 2020:6 p. Report No. WHO/NMH/NHD/MNM/20.5.
Watson PF, Petrie A. Method agreement analysis: a review of correct methodology. Theriogenology 2010; 73:1167-79.
Velasco-Rodriguez D, Alonso-Dominguez JM, Gonzalez-Fernandez FA, Villarrubia J, Ropero P, Martinez-Nieto J, et al. Deltabeta-thalassemia trait: how can we discriminate it from beta-thalassemia trait and iron deficiency anemia?. Am J Clin Pathol 2014; 142:567-73.
Brancaleoni V, Di Pierro E, Motta I, Cappellini MD. Laboratory diagnosis of thalassemia. Int J Lab Hematol 2016; 38:32-40.
Bain BJ. Blood cell morphology in health and disease. In: Bain BJ, Bates I, Laffan MA, editors. Dacie and Lewis practical haematology, 12th ed. Amsterdam: Elsevier; 2017.
Ford J. Red blood cell morphology. Int J Lab Hematol 2013; 35:351-7.
Bain BJ, Daniel Y, Henthorn J, de la Salle B, Hogan A, Roy NBA, et al. Significant haemoglobinopathies: a guideline for screening and diagnosis: a British society for haematology (BSH) guideline. Br J Haematol 2023; 201:1047-65.
Thilakarathne S, Jayaweera UP, Premawardhena A. Unresolved laboratory issues of the heterozygous state of beta-thalassemia: a literature review. Haematologica 2024; 109:23-32.
