{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:31:41Z","timestamp":1788787901683,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T00:00:00Z","timestamp":1577664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Iron\u2010deficiency contributes to a \u223c50% of anemia prevalence worldwide, but reference intervals for iron status tests are not optimized for anemia diagnosis. To address this limitation, we identified the serum ferritin (SF) thresholds associated with hematologic decline in iron\u2010deficient patients, and the SF thresholds from which an SF increase was associated with hematologic improvement. Paired red blood cell and SF measurements were analysed from two adult cohorts at Massachusetts General Hospital (MGH), from 2008\u20102011 (N = 48\u2009409), and 2016\u20102018 (N = 10\u2009042). Inter\u2010patient measurements in the first cohort were used to define optimal SF thresholds based on the physiologic relationship between SF and red cell measurements. Intra\u2010patient measurements (1\u201026\u2009weeks apart) in the second cohort were used to identify SF thresholds from which an SF increase was associated, with an increase in red cell measurements. The identified optimal SF thresholds varied with age, sex and red cell measure. Thresholds associated with a \u223c5% decline in red cell index were typically in the range 10\u201025\u2009ng\/mL. Thresholds for younger women (18\u201045\u2009year) were \u223c5\u2009ng\/mL lower than for older women (60\u201095\u2009years), and \u223c10\u2009ng\/mL lower than for men. Thresholds from which a subsequent increase in SF was associated with a concomitant increase in red cell measure showed similar patterns: younger women had lower thresholds (\u223c15\u2009ng\/mL) than older women (\u223c25\u2009ng\/mL), or men (\u223c35\u2009ng\/mL). These results suggest that diagnostic accuracy may be improved by setting different SF thresholds for younger women, older women, and men. This study illustrates how clinical databases may provide physiologic evidence for improved diagnostic thresholds.<\/jats:p>","DOI":"10.1002\/ajh.25706","type":"journal-article","created":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T01:13:10Z","timestamp":1576631590000},"page":"302-309","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Data\u2010driven physiologic thresholds for iron deficiency associated with hematologic decline"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0127-7311","authenticated-orcid":false,"given":"Brody H.","family":"Foy","sequence":"first","affiliation":[{"name":"Department of Pathology, and Center for Systems Biology Massachusetts General Hospital  Boston Massachusetts"},{"name":"Department of Systems Biology Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aodong","family":"Li","sequence":"additional","affiliation":[{"name":"Courant Institute of Mathematics, New York University  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"McClung","sequence":"additional","affiliation":[{"name":"Military Nutrition Divisions US Army Research Institute of Environmental Medicine  Natick Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Ranganath","sequence":"additional","affiliation":[{"name":"Courant Institute of Mathematics, New York University  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9182-0076","authenticated-orcid":false,"given":"John M.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Department of Pathology, and Center for Systems Biology Massachusetts General Hospital  Boston Massachusetts"},{"name":"Department of Systems Biology Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32154-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-508325"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02598003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60865-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000371618"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.3.1052"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V75.9.1870.1870"},{"key":"e_1_2_9_9_1","volume-title":"Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity","author":"WHO","year":"2011"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.117.155960"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.114.103366"},{"key":"e_1_2_9_12_1","first-page":"422","article-title":"Current misconceptions in diagnosis and management of iron deficiency","volume":"15","author":"Mu\u00f1oz M","year":"2017","journal-title":"Blood Transfus"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.5694\/j.1326-5377.2010.tb04038.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/27.7.681"},{"key":"e_1_2_9_15_1","volume-title":"Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline","author":"CLSI","year":"2008"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(14)00025-8"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15127"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-3046"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a009609"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2012-0377-OA"},{"key":"e_1_2_9_21_1","unstructured":"Center for Disease Control. 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