Non-Invasive Zinc Protoporphyrin Screening Offers Opportunities for Secondary Prevention of Iron Deficiency in Blood Donors
Background: Frequent blood donors are at high risk of developing iron deficiency. Currently, there is no potent screening during blood donation to detect iron deficient erythropoiesis (IDE) before anemia develops and deferral from donation is inevitable. Study Design and Methods: In addition to capi...
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| Published in | Transfusion Medicine and Hemotherapy Vol. 50; no. 4; pp. 303 - 312 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Basel, Switzerland
S. Karger AG
01.08.2023
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1660-3796 1660-3818 |
| DOI | 10.1159/000528545 |
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| Abstract | Background: Frequent blood donors are at high risk of developing iron deficiency. Currently, there is no potent screening during blood donation to detect iron deficient erythropoiesis (IDE) before anemia develops and deferral from donation is inevitable. Study Design and Methods: In addition to capillary and venous hemoglobin, the iron status of 99 frequent blood donors was assessed by various venous blood parameters and zinc protoporphyrin IX (ZnPP). ZnPP was determined by high-performance liquid chromatography (HPLC) and a new prototype fiber-optic device was employed for non-invasive measurements of ZnPP through the blood collection tubing (NI-tubing) and on lip tissue (NI-lip). We aimed to evaluate the feasibility and diagnostic value of the NI-tubing measurement for early detection of severe iron deficiency in blood donors. Results: NI-tubing and HPLC reference measurements of ZnPP showed narrow limits of agreement of 12.2 μmol ZnPP/mol heme and very high correlation (Spearman’s Rho = 0.938). Using a cutoff of 65 μmol ZnPP/mol heme, NI-tubing measurements (n = 93) identified 100% of donors with iron deficiency anemia (IDA) and an additional 38% of donors with IDE. Accordingly, NI-tubing measurements would allow detection and selective protection of particularly vulnerable donors. Conclusion: NI-tubing measurements are an accurate and simple method to implement ZnPP determination into the routine blood donation process. ZnPP was able to identify the majority of subjects with IDE and IDA and might therefore be a valuable tool to provide qualified information to donors about dietary measures and adjustments of the donation interval and thereby help to prevent IDA and hemoglobin deferral in the future. |
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| AbstractList | Background: Frequent blood donors are at high risk of developing iron deficiency. Currently, there is no potent screening during blood donation to detect iron deficient erythropoiesis (IDE) before anemia develops and deferral from donation is inevitable. Study Design and Methods: In addition to capillary and venous hemoglobin, the iron status of 99 frequent blood donors was assessed by various venous blood parameters and zinc protoporphyrin IX (ZnPP). ZnPP was determined by high-performance liquid chromatography (HPLC) and a new prototype fiber-optic device was employed for non-invasive measurements of ZnPP through the blood collection tubing (NI-tubing) and on lip tissue (NI-lip). We aimed to evaluate the feasibility and diagnostic value of the NI-tubing measurement for early detection of severe iron deficiency in blood donors. Results: NI-tubing and HPLC reference measurements of ZnPP showed narrow limits of agreement of 12.2 μmol ZnPP/mol heme and very high correlation (Spearman’s Rho = 0.938). Using a cutoff of 65 μmol ZnPP/mol heme, NI-tubing measurements (n = 93) identified 100% of donors with iron deficiency anemia (IDA) and an additional 38% of donors with IDE. Accordingly, NI-tubing measurements would allow detection and selective protection of particularly vulnerable donors. Conclusion: NI-tubing measurements are an accurate and simple method to implement ZnPP determination into the routine blood donation process. ZnPP was able to identify the majority of subjects with IDE and IDA and might therefore be a valuable tool to provide qualified information to donors about dietary measures and adjustments of the donation interval and thereby help to prevent IDA and hemoglobin deferral in the future. Background: Frequent blood donors are at high risk of developing iron deficiency. Currently, there is no potent screening during blood donation to detect iron deficient erythropoiesis (IDE) before anemia develops and deferral from donation is inevitable. Study Design and Methods: In addition to capillary and venous hemoglobin, the iron status of 99 frequent blood donors was assessed by various venous blood parameters and zinc protoporphyrin IX (ZnPP). ZnPP was determined by high-performance liquid chromatography (HPLC) and a new prototype fiber-optic device was employed for non-invasive measurements of ZnPP through the blood collection tubing (NI-tubing) and on lip tissue (NI-lip). We aimed to evaluate the feasibility and diagnostic value of the NI-tubing measurement for early detection of severe iron deficiency in blood donors. Results: NI-tubing and HPLC reference measurements of ZnPP showed narrow limits of agreement of 12.2 [mu]mol ZnPP/mol heme and very high correlation (Spearman's Rho = 0.938). Using a cutoff of 65 [mu]mol ZnPP/mol heme, NI-tubing measurements (n = 93) identified 100% of donors with iron deficiency anemia (IDA) and an additional 38% of donors with IDE. Accordingly, NI-tubing measurements would allow detection and selective protection of particularly vulnerable donors. Conclusion: NI-tubing measurements are an accurate and simple method to implement ZnPP determination into the routine blood donation process. ZnPP was able to identify the majority of subjects with IDE and IDA and might therefore be a valuable tool to provide qualified information to donors about dietary measures and adjustments of the donation interval and thereby help to prevent IDA and hemoglobin deferral in the future. Keywords: Iron deficiency, Erythropoiesis, Anemia, Zinc protoporphyrin, Blood donation Frequent blood donors are at high risk of developing iron deficiency. Currently, there is no potent screening during blood donation to detect iron deficient erythropoiesis (IDE) before anemia develops and deferral from donation is inevitable.BackgroundFrequent blood donors are at high risk of developing iron deficiency. Currently, there is no potent screening during blood donation to detect iron deficient erythropoiesis (IDE) before anemia develops and deferral from donation is inevitable.In addition to capillary and venous hemoglobin, the iron status of 99 frequent blood donors was assessed by various venous blood parameters and zinc protoporphyrin IX (ZnPP). ZnPP was determined by high-performance liquid chromatography (HPLC) and a new prototype fiber-optic device was employed for non-invasive measurements of ZnPP through the blood collection tubing (NI-tubing) and on lip tissue (NI-lip). We aimed to evaluate the feasibility and diagnostic value of the NI-tubing measurement for early detection of severe iron deficiency in blood donors.Study Design and MethodsIn addition to capillary and venous hemoglobin, the iron status of 99 frequent blood donors was assessed by various venous blood parameters and zinc protoporphyrin IX (ZnPP). ZnPP was determined by high-performance liquid chromatography (HPLC) and a new prototype fiber-optic device was employed for non-invasive measurements of ZnPP through the blood collection tubing (NI-tubing) and on lip tissue (NI-lip). We aimed to evaluate the feasibility and diagnostic value of the NI-tubing measurement for early detection of severe iron deficiency in blood donors.NI-tubing and HPLC reference measurements of ZnPP showed narrow limits of agreement of 12.2 μmol ZnPP/mol heme and very high correlation (Spearman's Rho = 0.938). Using a cutoff of 65 μmol ZnPP/mol heme, NI-tubing measurements (n = 93) identified 100% of donors with iron deficiency anemia (IDA) and an additional 38% of donors with IDE. Accordingly, NI-tubing measurements would allow detection and selective protection of particularly vulnerable donors.ResultsNI-tubing and HPLC reference measurements of ZnPP showed narrow limits of agreement of 12.2 μmol ZnPP/mol heme and very high correlation (Spearman's Rho = 0.938). Using a cutoff of 65 μmol ZnPP/mol heme, NI-tubing measurements (n = 93) identified 100% of donors with iron deficiency anemia (IDA) and an additional 38% of donors with IDE. Accordingly, NI-tubing measurements would allow detection and selective protection of particularly vulnerable donors.NI-tubing measurements are an accurate and simple method to implement ZnPP determination into the routine blood donation process. ZnPP was able to identify the majority of subjects with IDE and IDA and might therefore be a valuable tool to provide qualified information to donors about dietary measures and adjustments of the donation interval and thereby help to prevent IDA and hemoglobin deferral in the future.ConclusionNI-tubing measurements are an accurate and simple method to implement ZnPP determination into the routine blood donation process. ZnPP was able to identify the majority of subjects with IDE and IDA and might therefore be a valuable tool to provide qualified information to donors about dietary measures and adjustments of the donation interval and thereby help to prevent IDA and hemoglobin deferral in the future. |
| Audience | Academic |
| Author | Lang, Alexander Homann, Christian Quenzel, Ernst-Markus Hennig, Georg Holdt, Lesca Miriam Stepp, Herbert Weinauer, Franz Schliemann, Anne Sroka, Ronald Vogeser, Michael |
| AuthorAffiliation | d Blutspendedienst des Bayerischen Roten Kreuzes gemeinnützige GmbH, Munich, Germany c Institute of Laboratory Medicine, University Hospital, LMU Munich, Munich, Germany b Department of Urology, University Hospital, LMU Munich, Munich, Germany a Laser Research Laboratory, LIFE Center, University Hospital, LMU Munich, Munich, Germany |
| AuthorAffiliation_xml | – name: b Department of Urology, University Hospital, LMU Munich, Munich, Germany – name: d Blutspendedienst des Bayerischen Roten Kreuzes gemeinnützige GmbH, Munich, Germany – name: a Laser Research Laboratory, LIFE Center, University Hospital, LMU Munich, Munich, Germany – name: c Institute of Laboratory Medicine, University Hospital, LMU Munich, Munich, Germany |
| Author_xml | – sequence: 1 givenname: Anne surname: Schliemann fullname: Schliemann, Anne email: *Anne Schliemann, anne_schliemann@gmx.de – sequence: 2 givenname: Christian surname: Homann fullname: Homann, Christian – sequence: 3 givenname: Georg surname: Hennig fullname: Hennig, Georg – sequence: 4 givenname: Alexander surname: Lang fullname: Lang, Alexander – sequence: 5 givenname: Lesca Miriam surname: Holdt fullname: Holdt, Lesca Miriam – sequence: 6 givenname: Michael surname: Vogeser fullname: Vogeser, Michael – sequence: 7 givenname: Ronald surname: Sroka fullname: Sroka, Ronald – sequence: 8 givenname: Herbert orcidid: 0000-0002-1501-1912 surname: Stepp fullname: Stepp, Herbert – sequence: 9 givenname: Franz surname: Weinauer fullname: Weinauer, Franz – sequence: 10 givenname: Ernst-Markus orcidid: 0000-0001-8642-2324 surname: Quenzel fullname: Quenzel, Ernst-Markus |
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| Keywords | Erythropoiesis Iron deficiency Anemia Blood donation Zinc protoporphyrin |
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J Biophotonics. 2014 Jul;7(7):514–24. Homann C, Hennig G, Maier F, Stepp H, Holdt LM, Vogeser M, et al. Non-invasive measurement of erythrocyte zinc protoporphyrin in children. Pediatr Res. 2019 Feb;85(3):349–54. Hod EA, Brittenham GM, Bitan ZC, Feit Y, Gaelen JI, La Carpia F, et al. A randomized trial of blood donor iron repletion on red cell quality for transfusion and donor cognition and wellbeing. Blood. 2022 Sep 6:blood.2022017288. Baart AM, van Noord PAH, Vergouwe Y, Moons KGM, Swinkels DW, Wiegerinck ET. High prevalence of subclinical iron deficiency in whole blood donors not deferred for low hemoglobin. Transfusion. 2013 Aug;53(8):1670–7. Hastka J, Metzgeroth G, Gattermann N. Eisenmangel und Eisenmangelanämie, Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen. Onkopedia Leitlinien; 2021. Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Methods Med Res. 1999 Jun;8(2):135–60. Schifman RB, Rivers SL. Red blood cell zinc protoporphyrin to evaluate anemia risk in deferred blood donors. Am J Clin Pathol. 1987 Apr;87(4):511–4. Bundesärztekammer. (BÄK). Beschluss der Bundesärztekammer über die Richtlinie zur Gewinnung von Blut und Blutbestandteilen und zur Anwendung von Blutprodukten (Richtlinie Hämotherapie) – Gesamtnovelle 2017. Dtsch Arztebl. 2017;114(3132). A-1504/B-272/C-246. Waldvogel-Abramovski S, Waeber G, Gassner C, Buser A, Frey BM, Favrat B, et al. Iron and transfusion medicine. Blood Rev. 2013 Nov;27(6):289–95. Gorlin J, Katz L, Elsmore D, Kirbach K, Erickson Y, Hove A, et al. Prevalence of blood donor iron deficiency and feasibility ferritin-based iron replacement: a blood collection agency-based study. Vox Sang. 2016 Aug;111(2):206–8. Skikne BS. Serum transferrin receptor. Am J Hematol. 2008 Nov;83(11):872–5. Hennig G, Homann C, Teksan I, Hasbargen U, Hasmüller S, Holdt LM, et al. Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip. Nat Commun. 2016 Feb 17;7:10776. Radtke H, Tegtmeier J, Röcker L, Salama A, Kiesewetter H. Daily doses of 20 mg of elemental iron compensate for iron loss in regular blood donors: a randomized, double-blind, placebo-controlled study. Transfusion. 2004 Oct;44(10):1427–32. Spekman MLC, Ramondt S, Sweegers MG. Whole blood donor behavior and availability after deferral: consequences of a new ferritin monitoring policy. Transfusion. 2021 Apr;61(4):1112–21. Russell WA, Scheinker D, Custer B. Individualized risk trajectories for iron-related adverse outcomes in repeat blood donors. Transfusion. 2022 Jan;62(1):116–24. Hastka J, Lasserre JJ, Schwarzbeck A, Hehlmann R. Central role of zinc protoporphyrin in staging iron deficiency. Clin Chem. 1994 May;40(5):768–73. Ziemann M, Steppat D, Brockmann C, Washington G, Kirchner H, Schlenke P. Selection of whole-blood donors for hemoglobin testing by use of historical hemoglobin values. Transfusion. 2006 Dec;46(12):2176–83. Jensen BM, Sandø SH, Grandjean P, Wiggers P, Dalhøj J. Screening with zinc protoporphyrin for iron deficiency in non-anemic female blood donors. Clin Chem. 1990 Jun;36(6):846–8. Fliedner TM, Hoelzer D, Steinbach KH. [Physiological and pathological regulation of erythropoiesis]. Verh Dtsch Ges Inn Med. 1978(84):15–27. Füllenbach C, Stein P, Glaser P, Triphaus C, Lindau S, Choorapoikayil S, et al. Screening for iron deficiency in surgical patients based on noninvasive zinc protoporphyrin measurements. Transfusion. 2020 Jan;60(1):62–72. Sayers MH. Iron supplementation? Ferritin screening? Why questions persist. Transfusion. 2019 May;59(5):1616–9. Schifman RB, Rivers SL, Finley PR, Thies C. RBC zinc protoporphyrin to screen blood donors for iron deficiency anemia. JAMA. 1982 Oct 22;248(16):2012–5. Hillgrove T, Moore V, Doherty K, Ryan P. The impact of temporary deferral due to low hemoglobin: future return, time to return, and frequency of subsequent donation. Transfusion. 2011 Mar;51(3):539–47. Schifman RB, Finley PR. Measurement of near-normal concentrations of erythrocyte protoporphyrin with the hematofluorometer: influence of plasma on “front-surface illumination” assay. Clin Chem. 1981 Jan;27(1):153–6. Hastka J, Lasserre JJ, Schwarzbeck A, Strauch M, Hehlmann R. Washing erythrocytes to remove interferents in measurements of zinc protoporphyrin by front-face hematofluorometry. Clin Chem. 1992 Nov;38(11):2184–9. Schotten N, Zalpuri S, Pasker-de Jong PCM, Swinkels DW, van den Hurk K, de Kort WLAM, et al. Utility of zinc protoporphyrin in management of whole blood donors. Transfusion. 2018 Mar;58(3):692–700. Vassallo RR, Hilton JF, Bravo MD, Vittinghoff E, Custer B, Kamel H. Recovery of iron stores after adolescents donate blood. Pediatrics. 2020 Jul;146(1):e20193316. Harthoorn-Lasthuizen EJ, Lindemans J, Langenhuijsen MM. Zinc protoporphyrin as screening test in female blood donors. Clin Chem. 1998 Apr;44(4):800–4. Labbe RF, Vreman HJ, Stevenson DK. Zinc protoporphyrin: a metabolite with a mission. Clin Chem. 1999 Dec;45(12):2060–72. Heckl C, Eisel M, Lang A, Homann C, Paal M, Vogeser M, et al. Spectroscopic methods to quantify molecules of the heme-biosynthesis pathway: a review of laboratory work and point-of-care approaches. Translational Biophotonics. 2021;3(2):3. Brittenham GM, Klein HG, Kushner JP, Ajioka RS. Preserving the national blood supply. Hematology Am Soc Hematol Educ Program. 2001;422–32. Cable RG, Glynn SA, Kiss JE, Mast AE, Steele WR, Murphy EL, et al. Iron deficiency in blood donors: the REDS-II Donor Iron Status Evaluation (RISE) study. Transfusion. 2012 Apr;52(4):702–11. Finch CA, Cook JD, Labbe RF, Culala M. Effect of blood donation on iron stores as evaluated by serum ferritin. Blood. 1977 Sep;50(3):441–7. |
| References_xml | – reference: Russell WA, Scheinker D, Custer B. Individualized risk trajectories for iron-related adverse outcomes in repeat blood donors. Transfusion. 2022 Jan;62(1):116–24. – reference: Hennig G, Homann C, Teksan I, Hasbargen U, Hasmüller S, Holdt LM, et al. Non-invasive detection of iron deficiency by fluorescence measurement of erythrocyte zinc protoporphyrin in the lip. Nat Commun. 2016 Feb 17;7:10776. – reference: Baart AM, van Noord PAH, Vergouwe Y, Moons KGM, Swinkels DW, Wiegerinck ET. High prevalence of subclinical iron deficiency in whole blood donors not deferred for low hemoglobin. Transfusion. 2013 Aug;53(8):1670–7. – reference: Chua AC, Klopcic BR, Ho DS, Fu SK, Forrest CH, Croft KD, et al. Dietary iron enhances colonic inflammation and IL-6/IL-11-Stat3 signaling promoting colonic tumor development in mice. PLoS One. 2013;8(11):e78850. – reference: Radtke H, Tegtmeier J, Röcker L, Salama A, Kiesewetter H. Daily doses of 20 mg of elemental iron compensate for iron loss in regular blood donors: a randomized, double-blind, placebo-controlled study. Transfusion. 2004 Oct;44(10):1427–32. – reference: Finch CA, Cook JD, Labbe RF, Culala M. Effect of blood donation on iron stores as evaluated by serum ferritin. Blood. 1977 Sep;50(3):441–7. – reference: Hastka J, Lasserre JJ, Schwarzbeck A, Hehlmann R. Central role of zinc protoporphyrin in staging iron deficiency. Clin Chem. 1994 May;40(5):768–73. – reference: Hod EA, Brittenham GM, Bitan ZC, Feit Y, Gaelen JI, La Carpia F, et al. A randomized trial of blood donor iron repletion on red cell quality for transfusion and donor cognition and wellbeing. Blood. 2022 Sep 6:blood.2022017288. – reference: Hillgrove T, Moore V, Doherty K, Ryan P. The impact of temporary deferral due to low hemoglobin: future return, time to return, and frequency of subsequent donation. Transfusion. 2011 Mar;51(3):539–47. – reference: Gorlin J, Katz L, Elsmore D, Kirbach K, Erickson Y, Hove A, et al. Prevalence of blood donor iron deficiency and feasibility ferritin-based iron replacement: a blood collection agency-based study. Vox Sang. 2016 Aug;111(2):206–8. – reference: Spekman MLC, Ramondt S, Sweegers MG. Whole blood donor behavior and availability after deferral: consequences of a new ferritin monitoring policy. Transfusion. 2021 Apr;61(4):1112–21. – reference: Schifman RB, Rivers SL. Red blood cell zinc protoporphyrin to evaluate anemia risk in deferred blood donors. Am J Clin Pathol. 1987 Apr;87(4):511–4. – reference: Jensen BM, Sandø SH, Grandjean P, Wiggers P, Dalhøj J. Screening with zinc protoporphyrin for iron deficiency in non-anemic female blood donors. Clin Chem. 1990 Jun;36(6):846–8. – reference: Labbe RF, Vreman HJ, Stevenson DK. Zinc protoporphyrin: a metabolite with a mission. Clin Chem. 1999 Dec;45(12):2060–72. – reference: Hastka J, Metzgeroth G, Gattermann N. Eisenmangel und Eisenmangelanämie, Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen. Onkopedia Leitlinien; 2021. – reference: Cable RG, Glynn SA, Kiss JE, Mast AE, Steele WR, Murphy EL, et al. Iron deficiency in blood donors: the REDS-II Donor Iron Status Evaluation (RISE) study. Transfusion. 2012 Apr;52(4):702–11. – reference: Sayers MH. Iron supplementation? Ferritin screening? Why questions persist. Transfusion. 2019 May;59(5):1616–9. – reference: Schotten N, Zalpuri S, Pasker-de Jong PCM, Swinkels DW, van den Hurk K, de Kort WLAM, et al. Utility of zinc protoporphyrin in management of whole blood donors. Transfusion. 2018 Mar;58(3):692–700. – reference: Homann C, Hennig G, Maier F, Stepp H, Holdt LM, Vogeser M, et al. Non-invasive measurement of erythrocyte zinc protoporphyrin in children. 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| Snippet | Background: Frequent blood donors are at high risk of developing iron deficiency. Currently, there is no potent screening during blood donation to detect iron... Frequent blood donors are at high risk of developing iron deficiency. Currently, there is no potent screening during blood donation to detect iron deficient... |
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| SubjectTerms | Blood banks Blood donors Equipment and supplies Fiber optics Heme Hemoglobin High performance liquid chromatography Iron deficiency anemia Research Article Zinc protoporphyrin ; Anemia ; Blood donation ; Iron deficiency ; Erythropoiesis ; Research Article |
| Title | Non-Invasive Zinc Protoporphyrin Screening Offers Opportunities for Secondary Prevention of Iron Deficiency in Blood Donors |
| URI | https://karger.com/doi/10.1159/000528545 https://cir.nii.ac.jp/crid/1870020693140992896 https://www.proquest.com/docview/2870143679 https://pubmed.ncbi.nlm.nih.gov/PMC10521216 |
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