{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T09:58:24Z","timestamp":1781344704209,"version":"3.54.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T00:00:00Z","timestamp":1779494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medizinische Hochschule Hannover (MHH)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Iron deficiency assessment in myeloproliferative neoplasms is complicated by chronic inflammation, disease-related anemia, and treatment-induced changes in iron handling. We retrospectively analyzed 445 patients with MPN, including 158 with polycythemia vera, 97 with essential thrombocythemia, 44 with prefibrotic primary myelofibrosis, 127 with overt myelofibrosis, and 19 with MPN-unclassifiable, and compared conventional iron parameters with a population-based SHIP cohort of 4420 participants. ZPP was measured in the MPN cohort using quantitative fluorescence spectroscopy. Compared with SHIP, MPN patients had lower hemoglobin and higher ferritin, and the physiological positive correlation between ferritin and hemoglobin observed in SHIP was reversed in MPN patients, with\n                    <jats:italic>R<\/jats:italic>\n                    \u2009=\u20090.27, 95% CI 0.24 to 0.30,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001 in SHIP versus\n                    <jats:italic>R<\/jats:italic>\n                    \u2009=\u2009\u2212\u20090.45, 95% CI\u2009\u2212\u20090.52 to \u2212\u20090.36,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001 in MPN. Median ZPP in the MPN cohort was 43.0 \u00b5mol\/mol heme, with 123 of 445 patients (27.6%) showing ZPP values\u2009&gt;\u200965 \u00b5mol\/mol heme and 59 of 445 patients (13.3%) showing values\u2009&gt;\u2009100 \u00b5mol\/mol heme. ZPP differed significantly between MPN entities, with median values of 35.0 \u00b5mol\/mol heme in ET, 49.4 \u00b5mol\/mol heme in PV, 36.5 \u00b5mol\/mol heme in pre-PMF, 54.7 \u00b5mol\/mol heme in overt MF, and 46.0 \u00b5mol\/mol heme in MPN-U (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). ZPP correlated inversely with hemoglobin in MPN patients (\n                    <jats:italic>R<\/jats:italic>\n                    \u2009=\u2009\u2212\u20090.26, 95% CI\u2009\u2212\u20090.35 to \u2212\u20090.16,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), whereas its association with ferritin was weak (\n                    <jats:italic>R<\/jats:italic>\n                    \u2009=\u2009\u2212\u20090.10, 95% CI\u2009\u2212\u20090.20 to \u2212\u20090.00,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.045). Among 80 patients with CTCAE grade\u2009\u2265\u20092 anemia, 58 (73%) had ZPP values above the upper limit of normal. In exploratory multivariable analysis, PV, overt MF, and phlebotomy were independently associated with higher ZPP, whereas CRP and time from diagnosis were not. In JAK2-mutated PV versus ET, ZPP was significantly higher in PV (48.5 versus 37.5 \u00b5mol\/mol heme,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.010), complementing lower transferrin saturation and higher JAK2 variant allele frequency. These data indicate that ZPP provides a functional readout of iron-restricted heme synthesis in MPN, adds information beyond ferritin and transferrin saturation, and may refine diagnostic reassessment and therapeutic monitoring, particularly in PV and overt MF.\n                  <\/jats:p>","DOI":"10.1007\/s00277-026-07077-y","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T07:27:59Z","timestamp":1779521279000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Value of functional iron parameters in diagnostic re-assessment of MPN: refinement of iron-deficiency markers by zinc protoporphyrin (ZPP)"],"prefix":"10.1007","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-4076","authenticated-orcid":false,"given":"Kirsi","family":"Manz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Kobrosly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl C.","family":"Crodel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifa","family":"Al-Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Isfort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Kleppe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Neubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina M.","family":"Schn\u00f6der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Rogalski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Jilg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Stauch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Kr\u00fcger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kr\u00f6nke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hochhaus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Homann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2438-1955","authenticated-orcid":false,"given":"Florian H.","family":"Heidel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,23]]},"reference":[{"key":"7077_CR1","doi-asserted-by":"publisher","first-page":"a011668","DOI":"10.1101\/cshperspect.a011668","volume":"2","author":"T Ganz","year":"2012","unstructured":"Ganz T, Nemeth E (2012) Iron metabolism: interactions with normal and disordered erythropoiesis. Cold Spring Harb Perspect Med 2:a011668. https:\/\/doi.org\/10.1101\/cshperspect.a011668","journal-title":"Cold Spring Harb Perspect Med"},{"key":"7077_CR2","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s00277-025-06191-7","volume":"104","author":"M Griesshammer","year":"2025","unstructured":"Griesshammer M, Al-Ali HK, Eckardt J, Fiegl M, G\u00f6thert J, Jentsch-Ullrich K, Koschmieder S, Kvasnicka HM, Reiter A, Schmidt B, Heidel FH (2025) How I diagnose and treat patients in the pre-fibrotic phase of primary myelofibrosis (pre-PMF) - practical approaches of a German expert panel discussion in 2024. Ann Hematol 104:295\u2013306. https:\/\/doi.org\/10.1007\/s00277-025-06191-7","journal-title":"Ann Hematol"},{"key":"7077_CR3","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1038\/s41375-025-02569-8","volume":"39","author":"F Perner","year":"2025","unstructured":"Perner F, Pahl HL, Zeiser R, Heidel FH (2025) Malignant JAK-signaling: at the interface of inflammation and malignant transformation. Leukemia 39:1011\u20131030. https:\/\/doi.org\/10.1038\/s41375-025-02569-8","journal-title":"Leukemia"},{"key":"7077_CR4","doi-asserted-by":"publisher","first-page":"854","DOI":"10.3390\/cells8080854","volume":"8","author":"F Perner","year":"2019","unstructured":"Perner F, Perner C, Ernst T, Heidel FH (2019) Roles of JAK2 in Aging, Inflammation, Hematopoiesis and Malignant Transformation. Cells 8:854. https:\/\/doi.org\/10.3390\/cells8080854","journal-title":"Cells"},{"key":"7077_CR5","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/s00277-026-06774-y","volume":"105","author":"R Gonz\u00e1lez-Resina","year":"2026","unstructured":"Gonz\u00e1lez-Resina R, Espa\u00f1a-Fern\u00e1ndez de Valderrama S, Monta\u00f1\u00e9s \u00c1, Recasens V, Caballero G (2026) Diagnostic reassessment in myeloproliferative neoplasms: the value of functional iron parameters and JAK2 allelic burden. Ann Hematol 105:59\u2013y. https:\/\/doi.org\/10.1007\/s00277-026-06774-y","journal-title":"Ann Hematol"},{"key":"7077_CR6","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1093\/clinchem\/40.5.768","volume":"40","author":"J Hastka","year":"1994","unstructured":"Hastka J, Lasserre JJ, Schwarzbeck A, Hehlmann R (1994) Central role of zinc protoporphyrin in staging iron deficiency. Clin Chem 40:768\u2013773","journal-title":"Clin Chem"},{"key":"7077_CR7","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1182\/blood.V81.5.1200.1200","volume":"81","author":"J Hastka","year":"1993","unstructured":"Hastka J, Lasserre JJ, Schwarzbeck A, Strauch M, Hehlmann R (1993) Zinc protoporphyrin in anemia of chronic disorders. Blood 81:1200\u20131204","journal-title":"Blood"},{"key":"7077_CR8","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1111\/trf.15577","volume":"60","author":"C F\u00fcllenbach","year":"2020","unstructured":"F\u00fcllenbach C, Stein P, Glaser P, Triphaus C, Lindau S, Choorapoikayil S, Schmitt E, Zacharowski K, Hintereder G, Hennig G, Homann C, Stepp H, Spahn GH, Kaserer A, Schedler A, Meybohm P, Spahn DR (2020) Screening for iron deficiency in surgical patients based on noninvasive zinc protoporphyrin measurements. Transfusion 60:62\u201372. https:\/\/doi.org\/10.1111\/trf.15577","journal-title":"Transfusion"},{"key":"7077_CR9","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/j.1600-0609.2005.00515.x","volume":"75","author":"G Metzgeroth","year":"2005","unstructured":"Metzgeroth G, Adelberger V, Dorn-Beineke A, Kuhn C, Schatz M, Maywald O, Bertsch T, Wisser H, Hehlmann R, Hastka J (2005) Soluble transferrin receptor and zinc protoporphyrin\u2013competitors or efficient partners? Eur J Haematol 75:309\u2013317. https:\/\/doi.org\/10.1111\/j.1600-0609.2005.00515.x","journal-title":"Eur J Haematol"},{"key":"7077_CR10","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1007\/s00277-010-1089-8","volume":"90","author":"G Metzgeroth","year":"2011","unstructured":"Metzgeroth G, Kanders E, Erben P, Hofmann W, Hastka J (2011) The role of zinc protoporphyrin measurement in the differentiation between primary myelofibrosis and essential thrombocythaemia. Ann Hematol 90:389\u2013394. https:\/\/doi.org\/10.1007\/s00277-010-1089-8","journal-title":"Ann Hematol"},{"key":"7077_CR11","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1093\/clinchem\/38.11.2184","volume":"38","author":"J Hastka","year":"1992","unstructured":"Hastka J, Lasserre JJ, Schwarzbeck A, Strauch M, Hehlmann R (1992) Washing erythrocytes to remove interferents in measurements of zinc protoporphyrin by front-face hematofluorometry. Clin Chem 38:2184\u20132189","journal-title":"Clin Chem"},{"key":"7077_CR12","doi-asserted-by":"publisher","first-page":"10776","DOI":"10.1038\/ncomms10776","volume":"7","author":"G Hennig","year":"2016","unstructured":"Hennig G, Homann C, Teksan I, Hasbargen U, Hasm\u00fcller S, Holdt LM, Khaled N, Sroka R, Stauch T, Stepp H, Vogeser M, Brittenham GM (2016) Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip. Nat Commun 7:10776. https:\/\/doi.org\/10.1038\/ncomms10776","journal-title":"Nat Commun"},{"key":"7077_CR13","doi-asserted-by":"publisher","first-page":"e372","DOI":"10.1093\/ije\/dyac034","volume":"51","author":"H V\u00f6lzke","year":"2022","unstructured":"V\u00f6lzke H, Sch\u00f6ssow J, Schmidt CO, J\u00fcrgens C, Richter A, Werner A, Werner N, Radke D, Teumer A, Ittermann T, Schauer B, Henck V, Friedrich N, Hannemann A, Winter T, Nauck M, D\u00f6rr M, Bahls M, Felix SB, Stubbe B, Ewert R, Frost F, Lerch MM, Grabe HJ, B\u00fclow R, Otto M, Hosten N, Rathmann W, Schminke U, Gro\u00dfjohann R, Tost F, Homuth G, V\u00f6lker U, Weiss S, Holtfreter S, Br\u00f6ker BM, Zimmermann K, Kaderali L, Winnefeld M, Kristof B, Berger K, Samietz S, Schwahn C, Holtfreter B, Biffar R, Kindler S, Wittfeld K, Hoffmann W, Kocher T (2022) Cohort Profile Update: The Study of Health in Pomerania (SHIP). Int J Epidemiol 51:e372\u2013e383. https:\/\/doi.org\/10.1093\/ije\/dyac034","journal-title":"Int J Epidemiol"},{"key":"7077_CR14","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1038\/s41375-023-01943-8","volume":"37","author":"K Manz","year":"2023","unstructured":"Manz K, Bahr J, Ittermann T, D\u00f6hner K, Koschmieder S, Br\u00fcmmendorf TH, Griesshammer M, Nauck M, V\u00f6lzke H, Heidel FH (2023) Validation of myeloproliferative neoplasms associated risk factor RDW as predictor of thromboembolic complications in healthy individuals: analysis on 6849 participants of the SHIP-study. Leukemia 37:1745\u20131749. https:\/\/doi.org\/10.1038\/s41375-023-01943-8","journal-title":"Leukemia"},{"key":"7077_CR15","doi-asserted-by":"publisher","first-page":"2198","DOI":"10.1038\/s41375-020-0869-y","volume":"34","author":"D Midic","year":"2020","unstructured":"Midic D, Rinke J, Perner F, M\u00fcller V, Hinze A, Pester F, Landschulze J, Ernst J, Gruhn B, Matziolis G, Heidel FH, Hochhaus A, Ernst T (2020) Prevalence and dynamics of clonal hematopoiesis caused by leukemia-associated mutations in elderly individuals without hematologic disorders. Leukemia 34:2198\u20132205. https:\/\/doi.org\/10.1038\/s41375-020-0869-y","journal-title":"Leukemia"},{"key":"7077_CR16","unstructured":"R Core Team R (2025) R: A Language and Environment for Statistical Computing. https:\/\/www.R-project.org\/. Accessed 02 Apr 2026"},{"key":"7077_CR17","doi-asserted-by":"publisher","first-page":"2693","DOI":"10.1007\/s00432-021-03855-5","volume":"148","author":"CC Crodel","year":"2022","unstructured":"Crodel CC, Jentsch-Ullrich K, Reiser M, Jacobasch L, Sauer A, Tesch H, Ulsh\u00f6fer T, Wunschel R, Palandri F, Heidel FH (2022) Cytoreductive treatment in real life: a chart review analysis on 1440 patients with polycythemia vera. J Cancer Res Clin Oncol 148:2693\u20132705. https:\/\/doi.org\/10.1007\/s00432-021-03855-5","journal-title":"J Cancer Res Clin Oncol"},{"key":"7077_CR18","doi-asserted-by":"publisher","first-page":"3706","DOI":"10.3390\/cancers15143706","volume":"15","author":"F Palandri","year":"2023","unstructured":"Palandri F, Rossi E, Auteri G, Breccia M, Paglia S, Benevolo G, Elli EM, Cavazzini F, Binotto G, Tieghi A, Tiribelli M, Heidel FH, Bonifacio M, Pugliese N, Caocci G, Crugnola M, Mendicino F, D\u2019Addio A, Tomassetti S, Martino B, Polverelli N, Ceglie S, Mazzoni C, Mullai R, Ripamonti A, Garibaldi B, Pane F, Cuneo A, Krampera M, Semenzato G, Lemoli RM, Vianelli N, Palumbo GA, Andriani A, Cavo M, Latagliata R, De Stefano V (2023) Predictors of Response to Hydroxyurea and Switch to Ruxolitinib in HU-Resistant Polycythaemia VERA Patients: A Real-World PV-NET Study. Cancers (Basel) 15:3706. https:\/\/doi.org\/10.3390\/cancers15143706","journal-title":"Cancers (Basel)"},{"key":"7077_CR19","unstructured":"National Cancer Institute Cancer Therapy Evaluation Program (2017) Common Terminology Criteria for Adverse Events (CTCAE). Accessed 02 Apr 2026"},{"key":"7077_CR20","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/s41375-025-02524-7","volume":"39","author":"K Manz","year":"2025","unstructured":"Manz K, Heidel FH, Koschmieder S, Schlag R, Lipke J, Stegelmann F, Griesshammer M, Klausmann M, Crodel C, Hochhaus A, Schulz H, G\u00f6thert JR, Al-Ali H, Becker H, Reiter A, Beutel G, Kricheldorf K, Br\u00fcmmendorf TH, Hoffmann W, D\u00f6hner K, Isfort S (2025) Comparison of recognition of symptom burden in MPN between patient- and physician-reported assessment \u2013 an intraindividual analysis by the German Study Group for MPN (GSG-MPN). Leukemia 39:864\u2013875. https:\/\/doi.org\/10.1038\/s41375-025-02524-7","journal-title":"Leukemia"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-026-07077-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-07077-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-07077-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T09:48:20Z","timestamp":1781344100000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-026-07077-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,23]]},"references-count":20,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["7077"],"URL":"https:\/\/doi.org\/10.1007\/s00277-026-07077-y","relation":{},"ISSN":["1432-0584"],"issn-type":[{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,23]]},"assertion":[{"value":"16 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Christian Homann is shareholder and Managing Director of FerroSens GmbH, which developed the FIDscreen prototype device. The other authors do not have any relevant interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"294"}}