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To address this limitation, we aimed to translate the discovery of the \u03b1-thalassemia early eluting peak (\u03b1EEP) in HPLC into clinical practice by comparing its diagnostic performance with other existing methods (haemoglobin H inclusion test [HbHi] and immunochromatographic strip test [ICT]) in a multicentre setting, and elucidating the nature of the \u03b1EEP by liquid chromatography-tandem mass spectrometry (LC-MS\/MS). With a cohort of 820 genotyped patients, the \u03b1EEP showed superior diagnostic performance in detecting --\n                    <jats:sup>SEA<\/jats:sup>\n                    (sensitivity 99.6%, specificity 100%) compared with HbHi (sensitivity 95.8%,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.006; specificity 97.3%,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001) and ICT (sensitivity 95.8%,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.006; specificity 75.4%,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). Both HbHi and ICT showed reduced sensitivity in \u03b2-thalassaemia carriers versus non-carriers. ICT showed reduced specificity when Hb F\u2009\u2265\u20091% compared with &lt;\u20091%. The \u03b1EEP remained robust across all subgroups. LC-MS\/MS revealed a strong association between the \u03b1EEP and embryonic \u03b6-globin chains (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u20090.001). The \u03b1EEP offered cost reductions of 98.6% over HbHi and 97.3% over ICT. Collectively, the \u03b1EEP is a highly reliable and cost-effective marker for detecting --\n                    <jats:sup>SEA<\/jats:sup>\n                    carriers, enabling a novel \u201call-in-one\u201d HPLC screening strategy for --\n                    <jats:sup>SEA<\/jats:sup>\n                    , \u03b2-thalassaemia and haemoglobinopathies. Trial registration number: not applicable.\n                  <\/jats:p>","DOI":"10.1007\/s00277-026-07102-0","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T09:35:04Z","timestamp":1781861704000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alpha-thalassaemia early eluting peak for alpha-thalassaemia --SEA carrier screening: a multicentre diagnostic comparison with immunochromatographic strip test and haemoglobin H inclusion test"],"prefix":"10.1007","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6454-5729","authenticated-orcid":false,"given":"Wing Kit","family":"Lam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen Michelle","family":"Yuen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence Lap 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