{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T05:57:07Z","timestamp":1769147827291,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,7,13]],"date-time":"2018-07-13T00:00:00Z","timestamp":1531440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["#1P20GM104317\u201001"],"award-info":[{"award-number":["#1P20GM104317\u201001"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>South\u2010East Asian ovalocytosis (<jats:styled-content style=\"fixed-case\">SAO<\/jats:styled-content>) is a common inherited red blood cell polymorphism in South\u2010East Asian and Melanesian populations, coinciding with areas of malaria endemicity. Validation of light microscopy as a diagnostic alternative to molecular genotyping may allow for its cost\u2010effective use either prospectively or retrospectively by analysis of archived blood smears.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed light microscopic diagnosis of <jats:styled-content style=\"fixed-case\">SAO<\/jats:styled-content> compared to standard <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> genotyping. Three trained microscopists each assessed the same 971 Giemsa\u2010stained thin blood films for which <jats:styled-content style=\"fixed-case\">SAO<\/jats:styled-content> genotypic confirmation was available by <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>. Generalized mixed modeling was used to estimate the sensitivity, specificity, positive predictive value, and negative predictive value of light microscopy vs \u201cgold standard\u201d <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among red cell morphologic parameters evaluated, knizocytes, rather than ovalocytic morphology, proved the strongest predictor of <jats:styled-content style=\"fixed-case\">SAO<\/jats:styled-content> status (odds ratio [<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>]\u00a0=\u00a019.2; 95% confidence interval [95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>]\u00a0=\u00a014.6\u201025.3; <jats:italic>P<\/jats:italic>\u00a0\u2264\u00a00.0001). The diagnostic performance of a knizocyte\u2010centric microscopic approach was microscopist dependent: two microscopists applied this approach with a sensitivity of 0.89 and a specificity of 0.93. Inter\u2010rater reliability among the microscopists (\u03ba\u00a0=\u00a00.20) as well as between gold standard and microscopist (\u03ba\u00a0=\u00a00.36) underperformed due to misclassification of stomatocytes as knizocytes by one microscopist, but improved substantially when excluding the error\u2010prone reader (\u03ba\u00a0=\u00a00.65 and 0.74, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Light microscopic diagnosis of <jats:styled-content style=\"fixed-case\">SAO<\/jats:styled-content> by knizocyte visual cue performed comparable to time\u2010consuming and costlier molecular methods, but requires specific training that includes successful differentiation of knizocytes from stomatocytes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.12900","type":"journal-article","created":{"date-parts":[[2018,7,14]],"date-time":"2018-07-14T06:24:30Z","timestamp":1531549470000},"page":"655-662","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Accurate light microscopic diagnosis of South\u2010East Asian ovalocytosis"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9243-5567","authenticated-orcid":false,"given":"Christian P.","family":"Nixon","sequence":"first","affiliation":[{"name":"Center for International Health Research Rhode Island Hospital and Alpert Medical School of Brown University  Providence Rhode Island"},{"name":"Department of Transfusion Medicine Rhode Island Hospital and the Miriam Hospitals  Providence Rhode Island"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ari W.","family":"Satyagraha","sequence":"additional","affiliation":[{"name":"Eijkman Institute for Molecular Biology  Jakarta Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grayson L.","family":"Baird","sequence":"additional","affiliation":[{"name":"Lifespan Biostatistics Core Rhode Island Hospital  Providence Rhode Island"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alida R.","family":"Harahap","sequence":"additional","affiliation":[{"name":"Eijkman Institute for Molecular Biology  Jakarta Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia V.","family":"Panggalo","sequence":"additional","affiliation":[{"name":"Eijkman Institute for Molecular Biology  Jakarta Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lenny L.","family":"Ekawati","sequence":"additional","affiliation":[{"name":"Eijkman\u2010Oxford Clinical Research Unit Eijkman Institute for Molecular Biology  Jakarta 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