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Red cell units from such blood donors with <jats:italic>DEL<\/jats:italic> alleles are RhD protein-positive, despite being routinely labelled D-negative. Molecular typing offers a more sensitive method to identify Del individuals by detecting the presence of the <jats:italic>RHD<\/jats:italic> gene. Pools of 20 or more donor samples are routinely screened for the <jats:italic>RHD<\/jats:italic> gene in some, mostly European, donor populations. <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A modular real-time PCR assay targeting <jats:italic>RHD<\/jats:italic> intron 4, exon 5, and exon 7 was developed for individual testing. We screened for the <jats:italic>RHD<\/jats:italic> gene among all blood donors who typed D-negative in routine serology.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Over 15\u00a0years, 2254 D-negative donors were individually tested for the <jats:italic>RHD<\/jats:italic> gene. With a sensitivity of detecting 5 <jats:italic>RHD<\/jats:italic> positive gDNA copies per reaction, 42 donors tested positive (1.9%). Among them, 34 carried the common <jats:italic>RHD\u03a8<\/jats:italic> allele (80.9%), while 7 harbored 5 known <jats:italic>RHD<\/jats:italic> alleles, and 1 a novel <jats:italic>RHD<\/jats:italic> deletion. We inadvertently detected 2 other donors with DVI, establishing a population frequency of 1 in 731 for the U.S.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>A modular approach for <jats:italic>RHD<\/jats:italic> screening is suitable for blood donors when sample pooling is not feasible among multiethnic donor populations. We transitioned donors since 2009 from serologic D-negative to molecularly <jats:italic>RHD<\/jats:italic>-negative status at the NIH Clinical Center. Molecular <jats:italic>RHD<\/jats:italic> screening of serologic D-negative donors is an effective way to identify individuals harboring <jats:italic>DEL<\/jats:italic> alleles that can cause alloimmunization in transfusion recipients.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12967-025-06716-8","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T14:03:34Z","timestamp":1750341814000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Transitioning a multiethnic donor pool from serologic D-negative to molecularly RHD-negative at a hospital-based blood donor service"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1631-7198","authenticated-orcid":false,"given":"Willy A.","family":"Flegel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3658-0815","authenticated-orcid":false,"given":"Kshitij","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0754-097X","authenticated-orcid":false,"given":"Lorraine G.","family":"Caruccio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1171-7643","authenticated-orcid":false,"given":"Pirmin","family":"Schmid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Stiles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina U.","family":"Bueno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine R.","family":"Dowling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8896-6485","authenticated-orcid":false,"given":"Traci D.","family":"Paige","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sita","family":"Shrestha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"6716_CR1","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.transci.2010.12.013","volume":"44","author":"WA Flegel","year":"2011","unstructured":"Flegel WA. 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