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Carpentier T, Merlin A, Cappe A, Metzelard M, Villeret L, Jeanjean P, Mahjoub Y, Maizel J, Dupont H, Malaquin S, Mary A. Erythropoietin in ICU patients receiving early red blood cell transfusions: A retrospective study of the impact on transfusion requirements. J Crit Care 2025; 88:155052. [PMID: 40112672 DOI: 10.1016/j.jcrc.2025.155052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 02/17/2025] [Accepted: 03/02/2025] [Indexed: 03/22/2025]
Abstract
PURPOSE Anemia correlates with increased ICU mortality; but the use of erythropoietin (EPO) as a treatment remains debated. We sought to assess EPO use in ICU severe anemia. METHODS A retrospective single-center study was conducted in four adult ICUs. Inclusion criteria were ICU stay ≥10 days (to limit immortality bias) and RBC transfusion within the first 48 h (an indication of severe anemia likely to justify EPO). EPO contraindication was an exclusion criterion. Univariate tests were followed by a multivariable analysis. RESULTS Over a 28-month period, 190 patients (69 with EPO) were included. EPO subgroups displayed had a higher prevalence of hemorrhagic shock and surgical ICU admissions. EPO administration was significantly associated with a lower requirement for late RBC transfusions in trauma and non-trauma subgroups, with odds ratios [95 % confidence interval] of 0.29 [0.10-0.85] and 0.03 [0.004-0.18], respectively. In the EPO subgroup, the median hemoglobin level rose by 1.2 g/dL. Cox model showed a significant association with mortality at day 28 and 365. CONCLUSION Our study supports the hypothesis whereby EPO administration in severely anemic ICU patients reduces late transfusion needs, with a potentially higher survival rate. Systematic EPO use post-RBC transfusion in ICU patients warrants further investigation.
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Affiliation(s)
- Thomas Carpentier
- Amiens University Medical Center, Clinical Pharmacy Department, F-80054 Amiens, France
| | - Anthony Merlin
- Amiens University Medical Center, Clinical Pharmacy Department, F-80054 Amiens, France
| | - Arnaud Cappe
- Amiens University Medical Center, Clinical Pharmacy Department, F-80054 Amiens, France; Montdidier-Roye General Hospital, Pharmacy Department, F-80500 Montdidier, France
| | - Matthieu Metzelard
- Amiens University Medical Center, Surgical Intensive Care Unit, F-80054 Amiens, France
| | - Léonie Villeret
- Amiens University Medical Center, Surgical Intensive Care Unit, F-80054 Amiens, France
| | - Patrick Jeanjean
- Amiens University Medical Center, Neurological Intensive Care Unit, F-80054 Amiens, France
| | - Yazine Mahjoub
- Amiens University Medical Center, Cardiovascular and Thoracic Intensive Care Unit, F-80054 Amiens, France; UR 7518 UPJV, Simplification des soins chez les patients complexes (SSPC), Jules Verne University of Picardie, F-80025 Amiens, France
| | - Julien Maizel
- Amiens University Medical Center, Medical Intensive Care Unit, F-80054 Amiens, France; UR 7517 UPJV, Pathophysiological mechanisms and consequences of cardiovascular calcifications (MP3CV), Jules Verne University of Picardie, F-80025 Amiens, France
| | - Hervé Dupont
- Amiens University Medical Center, Surgical Intensive Care Unit, F-80054 Amiens, France; Amiens University Medical Center, Neurological Intensive Care Unit, F-80054 Amiens, France; Amiens University Medical Center, Cardiovascular and Thoracic Intensive Care Unit, F-80054 Amiens, France; UR 7518 UPJV, Simplification des soins chez les patients complexes (SSPC), Jules Verne University of Picardie, F-80025 Amiens, France
| | - Stéphanie Malaquin
- Amiens University Medical Center, Surgical Intensive Care Unit, F-80054 Amiens, France
| | - Aurélien Mary
- Amiens University Medical Center, Clinical Pharmacy Department, F-80054 Amiens, France; UR 7517 UPJV, Pathophysiological mechanisms and consequences of cardiovascular calcifications (MP3CV), Jules Verne University of Picardie, F-80025 Amiens, France.
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Appiah SK, Nkansah C, Appiah GA, Abbam G, Osei-Boakye F, Daud S, Mensah K, Adwoa S, Kuwaahsuore KS, Yeboah E, Tiyumba ASS, Thompson D, Paula VM, Duibajia LA, Takyia P, Kwarteng FA, Asiedu OO, Sukasorr FI, Kawuribi V, Ukwah BN, Chukwurah EF. Erythroferrone-Driven Regulation of Hepcidin and Iron Levels in Polytransfused Sickle Cell Anaemia Patients: A Prospective Study. BIOMED RESEARCH INTERNATIONAL 2025; 2025:6803051. [PMID: 40177293 PMCID: PMC11964725 DOI: 10.1155/bmri/6803051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Accepted: 02/01/2025] [Indexed: 04/05/2025]
Abstract
The interplay of erythroferrone (ERFE), hepcidin, and ferroportin is crucial for ensuring systemic iron homeostasis. This study determined the influence of ERFE on hepcidin and iron levels in polytransfused patients with sickle cell anaemia (SCA). This multicentre case-control study recruited 60 SCA participants and 30 controls (HbA), aged 2-34 years, from Tamale Teaching Hospital; Methodist Hospital, Wenchi; and Seventh Day Adventist Hospital, Sunyani, Ghana, between the periods of March to July 2023. About 4 mL of blood was collected for a full blood count using a haematology analyzer and serum ERFE, hepcidin, ferroportin, and ferritin estimation using an enzyme-linked immunosorbent assay. Data were analyzed using SPSS Version 26.0. ERFE (p < 0.001), ferroportin (p = 0.016), ferritin (p < 0.001), serum iron (p < 0.001), transferrin (p = 0.001), soluble transferrin receptor (sTFR) (p = 0.019), TWBC (p < 0.001), and platelet (p < 0.001) were significantly higher in SCA participants and hydroxyurea-naïve participants than in the control group and hydroxyurea-treated participants, respectively. Levels of hepcidin (p < 0.001), red blood cell (p < 0.001), haemoglobin (p < 0.001), and haematocrit (p < 0.001) were lower in the SCA and hydroxyurea-naïve groups than in the control and hydroxyurea-treated groups, respectively. An inverse correlation was observed between serum ERFE and hepcidin (r = -0.391, p = 0.002) and hepcidin and ferroportin (r = -0.266, p = 0.040), while ferritin (r = 0.439, p < 0.001) and ferroportin (r = 0.309, p = 0.016) showed a positive correlation with ERFE. No correlation was found between serum hepcidin and ferritin levels (r = 0.025, p = 0.853). Again, participants with regular blood transfusions had significantly higher levels of ERFE (p < 0.001) and ferritin (p = 0.002) than those with rare and no transfusions per year. None of the SCA participants had done iron testing. In conclusion, the negative impact of ERFE on hepcidin levels may exacerbate the risk of iron burden, as evident by elevated iron levels in SCA patients and the need for regular monitoring of the iron status of polytransfused SCA patients.
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Affiliation(s)
- Samuel Kwasi Appiah
- Department of Haematology, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
- Department of Medical Laboratory Science, Faculty of Health Science and Technology, Ebonyi State University, Abakaliki, Nigeria
| | - Charles Nkansah
- Department of Haematology, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
- Department of Medical Laboratory Science, Faculty of Health Science and Technology, Ebonyi State University, Abakaliki, Nigeria
| | - Godfred Amoah Appiah
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Gabriel Abbam
- Department of Haematology, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Felix Osei-Boakye
- Department of Medical Laboratory Science, Faculty of Health Science and Technology, Ebonyi State University, Abakaliki, Nigeria
- Department of Medical Laboratory Technology, Faculty of Applied Science and Technology, Sunyani Technical University, Sunyani, Ghana
| | - Samira Daud
- Department of Haematology, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Kofi Mensah
- Department of Haematology, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
- Department of Medical Laboratory Science, Faculty of Health Science and Technology, Ebonyi State University, Abakaliki, Nigeria
| | - Safo Adwoa
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Korah Seedolf Kuwaahsuore
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Emmanuel Yeboah
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Abu Siraj Salma Tiyumba
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Dennis Thompson
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Viel Mary Paula
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Louis Adda Duibajia
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Peter Takyia
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Franklina Ataa Kwarteng
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Obed Odame Asiedu
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Firdaus Ibrahim Sukasorr
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Vincent Kawuribi
- Department of Biomedical Laboratory Sciences, School of Allied Health Sciences, University for Development Studies, Tamale, Ghana
| | - Boniface Nwofoke Ukwah
- Department of Medical Laboratory Science, Faculty of Health Science and Technology, Ebonyi State University, Abakaliki, Nigeria
| | - Ejike Felix Chukwurah
- Department of Medical Laboratory Science, Faculty of Health Science and Technology, Ebonyi State University, Abakaliki, Nigeria
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Casarin F, Mascolo R, Motta I, Wu MA, Bizzi E, Pedroli A, Dieguez G, Iacomelli G, Serati L, Duca L, Maestroni S, Tombetti E, Cappellini MD, Brucato A. Decrease in Hemoglobin Levels during Acute Attacks in Patients with Idiopathic Recurrent Pericarditis: A Model of Anemia in Acute Disease. J Clin Med 2024; 13:5944. [PMID: 39408004 PMCID: PMC11478241 DOI: 10.3390/jcm13195944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Revised: 09/28/2024] [Accepted: 10/02/2024] [Indexed: 10/20/2024] Open
Abstract
Background/Objectives: Anemia during acute inflammation is not well described in the literature. We aimed to study whether patients develop a transient hemoglobin decrease during an acute attack of recurrent pericarditis. Methods: We retrospectively analyzed patients with recurrent pericarditis. The primary endpoint was the difference in hemoglobin levels during an acute attack and in the following remission. As secondary endpoints, we correlated this variation with laboratory and clinical features; we also evaluated the available baseline hemoglobin values. Results: Sixty-two patients, including thirty females (48.4%), with a median age of 39 years, were observed during an acute attack and remission. The attack indexed was the first in 21 patients and the second or the third in 41, with pre-attack hemoglobin levels available for the latter group. Median hemoglobin levels (IQR) were 13.8 (12.8-15.1) g/dL at baseline, 12.0 (11.2-13.4) during attacks and 13.6 (13.1-14.0) during remission (p < 0.001). The median hemoglobin reduction between an acute attack and remission was 1.4 g/dL. Their mean corpuscular volume remained in the normal range. Hb reduction significantly correlated with C-reactive protein (CRP) elevation, neutrophilia and the neutrophil-to-lymphocyte ratio, but not serosal involvement. Only CRP elevation remained associated with the variation of Hb in a multivariate analysis (p = 0.007). Conclusions: This study is a proof of concept: hemoglobin levels may decline rapidly during acute inflammation in correlation with CRP elevation, with transient normocytic anemia, followed by a rapid rebound. In this regard, idiopathic pericarditis may represent a pathogenetic model of this type of anemia.
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Affiliation(s)
- Francesca Casarin
- Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Fatebenefratelli Hospital, 20121 Milan, Italy; (F.C.); (E.B.); (A.P.); (G.D.); (G.I.); (L.S.); (E.T.); (A.B.)
- Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli-Sacco, University of Milan, 20157 Milan, Italy
| | - Ruggiero Mascolo
- Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Fatebenefratelli Hospital, 20121 Milan, Italy; (F.C.); (E.B.); (A.P.); (G.D.); (G.I.); (L.S.); (E.T.); (A.B.)
- Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli-Sacco, University of Milan, 20157 Milan, Italy
| | - Irene Motta
- Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy;
- SC Medicina ad Indirizzo Metabolico, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (L.D.); (M.D.C.)
| | - Maddalena Alessandra Wu
- Division of Internal Medicine, ASST Fatebenefratelli-Sacco, Luigi Sacco Hospital, University of Milan, 20157 Milan, Italy;
| | - Emanuele Bizzi
- Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Fatebenefratelli Hospital, 20121 Milan, Italy; (F.C.); (E.B.); (A.P.); (G.D.); (G.I.); (L.S.); (E.T.); (A.B.)
| | - Alice Pedroli
- Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Fatebenefratelli Hospital, 20121 Milan, Italy; (F.C.); (E.B.); (A.P.); (G.D.); (G.I.); (L.S.); (E.T.); (A.B.)
- Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli-Sacco, University of Milan, 20157 Milan, Italy
| | - Giulia Dieguez
- Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Fatebenefratelli Hospital, 20121 Milan, Italy; (F.C.); (E.B.); (A.P.); (G.D.); (G.I.); (L.S.); (E.T.); (A.B.)
- Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli-Sacco, University of Milan, 20157 Milan, Italy
| | - Giacomo Iacomelli
- Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Fatebenefratelli Hospital, 20121 Milan, Italy; (F.C.); (E.B.); (A.P.); (G.D.); (G.I.); (L.S.); (E.T.); (A.B.)
- Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli-Sacco, University of Milan, 20157 Milan, Italy
| | - Lisa Serati
- Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Fatebenefratelli Hospital, 20121 Milan, Italy; (F.C.); (E.B.); (A.P.); (G.D.); (G.I.); (L.S.); (E.T.); (A.B.)
- Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli-Sacco, University of Milan, 20157 Milan, Italy
| | - Lorena Duca
- SC Medicina ad Indirizzo Metabolico, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (L.D.); (M.D.C.)
| | - Silvia Maestroni
- Department of Internal Medicine, Ospedale Papa Giovanni XXIII, 24127 Bergamo, Italy;
| | - Enrico Tombetti
- Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Fatebenefratelli Hospital, 20121 Milan, Italy; (F.C.); (E.B.); (A.P.); (G.D.); (G.I.); (L.S.); (E.T.); (A.B.)
- Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli-Sacco, University of Milan, 20157 Milan, Italy
| | - Maria Domenica Cappellini
- SC Medicina ad Indirizzo Metabolico, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (L.D.); (M.D.C.)
| | - Antonio Brucato
- Department of Internal Medicine, ASST Fatebenefratelli-Sacco, Fatebenefratelli Hospital, 20121 Milan, Italy; (F.C.); (E.B.); (A.P.); (G.D.); (G.I.); (L.S.); (E.T.); (A.B.)
- Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli-Sacco, University of Milan, 20157 Milan, Italy
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Neri S, Brandsma ET, Mul FPJ, Kuijpers TW, Matlung HL, van Bruggen R. An AI-based imaging flow cytometry approach to study erythrophagocytosis. Cytometry A 2024; 105:763-771. [PMID: 39248056 DOI: 10.1002/cyto.a.24894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 07/03/2024] [Accepted: 07/26/2024] [Indexed: 09/10/2024]
Abstract
Erythrophagocytosis is a process consisting of recognition, engulfment and digestion by phagocytes of antibody-coated or damaged erythrocytes. Understanding the dynamics that are behind erythrophagocytosis is fundamental to comprehend this cellular process under specific circumstances. Several techniques have been used to study phagocytosis. Among these, an interesting approach is the use of Imaging Flow Cytometry (IFC) to distinguish internalization and binding of cells or particles. However, this method requires laborious analysis. Here, we introduce a novel approach to analyze the phagocytosis process by combining Artificial Intelligence (AI) with IFC. Our study demonstrates that this approach is highly suitable to study erythrophagocytosis, categorizing internalized, bound and non-bound erythrocytes. Validation experiments showed that our pipeline performs with high accuracy and reproducibility.
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Affiliation(s)
- S Neri
- Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, Amsterdam, The Netherlands
| | - E T Brandsma
- Saxion, Academy Life Science Engineering and Design, University of Applied Science, Enschede, The Netherlands
| | - F P J Mul
- Department Central Cell Analysis Facility, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - T W Kuijpers
- Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, Amsterdam, The Netherlands
| | - H L Matlung
- Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, Amsterdam, The Netherlands
| | - R van Bruggen
- Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, Amsterdam, The Netherlands
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Mishra A, Juneja D. Deciphering the iron enigma: Navigating the complexities of iron metabolism in critical illness. World J Clin Cases 2024; 12:6027-6031. [PMID: 39328848 PMCID: PMC11326100 DOI: 10.12998/wjcc.v12.i27.6027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 05/30/2024] [Accepted: 06/20/2024] [Indexed: 07/29/2024] Open
Abstract
Iron is a double-edged sword! Despite being essential for numerous physiological processes of the body, a dysregulated iron metabolism can result in tissue damage, exaggerated inflammatory response, and increased susceptibility to infection with certain pathogens that thrive in iron-rich environment. During sepsis, there is an alteration of iron metabolism, leading to increased transport and uptake into cells. This increase in labile iron may cause oxidative damage and cellular injury (ferroptosis) which progresses as the disease worsens. Critically ill patients are often complicated with systemic inflammation which may contribute to multiple organ dysfunction syndrome or sepsis, a common cause of mortality in intensive care unit. Originally, ferritin was known to play an important role in the hematopoietic system for its iron storage capacity. Recently, its role has emerged as a predictor of poor prognosis in chronic inflammation and critical illnesses. Apart from predicting the disease outcome, serum ferritin can potentially reflect disease activity as well.
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Affiliation(s)
- Anjali Mishra
- Department of Critical Care Medicine, Holy Family Hospital, Delhi 110025, India
| | - Deven Juneja
- Department of Critical Care Medicine, Max Super Speciality Hospital, New Delhi 110017, India
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Schmidtner N, Utrata A, Mester P, Schmid S, Müller M, Pavel V, Buechler C. Reduced Plasma Bone Morphogenetic Protein 6 Levels in Sepsis and Septic Shock Patients. Biomedicines 2024; 12:1682. [PMID: 39200147 PMCID: PMC11351235 DOI: 10.3390/biomedicines12081682] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/22/2024] [Accepted: 07/24/2024] [Indexed: 09/01/2024] Open
Abstract
Infectious diseases are associated with low iron levels and the induction of hepcidin, the primary protein regulating cellular iron export. Bone morphogenetic protein 6 (BMP6), a key regulator of hepcidin expression, has not yet been analyzed in the plasma of patients with systemic inflammatory response syndrome (SIRS) or sepsis. An analysis of 38 SIRS, 39 sepsis, and 78 septic shock patients revealed similar levels of BMP6 in sepsis and septic shock, which were lower compared to patients with SIRS and healthy controls. Plasma BMP6 levels did not correlate with procalcitonin and C-reactive protein levels in patients with SIRS or sepsis/septic shock. Neither bacterial nor SARS-CoV-2 infections affected plasma BMP6 levels. There was no difference in BMP6 levels between ventilated and non-ventilated patients, or between patients with and without dialysis. Vasopressor therapy did not alter BMP6 levels. Survivors had plasma BMP6 levels similar to non-survivors. Due to the high variability of plasma BMP6 levels, these analyses have limited clinical relevance. Iron, ferritin, and transferrin levels were known in at least 50% of patients but did not correlate with plasma BMP6 levels. In conclusion, this study showed normal BMP6 plasma levels in SIRS, which are reduced in patients with sepsis and septic shock. This suggests that the commonly observed increase in hepcidin levels and the decline in iron levels in SIRS, sepsis, and septic shock are not due to higher BMP6.
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Yang DC, Zheng BJ, Li J, Yu Y. Iron and ferritin effects on intensive care unit mortality: A meta-analysis. World J Clin Cases 2024; 12:2803-2812. [PMID: 38899309 PMCID: PMC11185325 DOI: 10.12998/wjcc.v12.i16.2803] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 03/07/2024] [Accepted: 04/11/2024] [Indexed: 05/29/2024] Open
Abstract
BACKGROUND The effect of serum iron or ferritin parameters on mortality among critically ill patients is not well characterized. AIM To determine the association between serum iron or ferritin parameters and mortality among critically ill patients. METHODS Web of Science, Embase, PubMed, and Cochrane Library databases were searched for studies on serum iron or ferritin parameters and mortality among critically ill patients. Two reviewers independently assessed, selected, and abstracted data from studies reporting on serum iron or ferritin parameters and mortality among critically ill patients. Data on serum iron or ferritin levels, mortality, and demographics were extracted. RESULTS Nineteen studies comprising 125490 patients were eligible for inclusion. We observed a slight negative effect of serum ferritin on mortality in the United States population [relative risk (RR) 1.002; 95%CI: 1.002-1.004). In patients with sepsis, serum iron had a significant negative effect on mortality (RR = 1.567; 95%CI: 1.208-1.925). CONCLUSION This systematic review presents evidence of a negative correlation between serum iron levels and mortality among patients with sepsis. Furthermore, it reveals a minor yet adverse impact of serum ferritin on mortality among the United States population.
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Affiliation(s)
- Deng-Can Yang
- Department of Anesthesiology, The Central Hospital of Shaoyang, Shaoyang 422000, Hunan Province, China
| | - Bo-Jun Zheng
- Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Jian Li
- Department of Critical Care Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong Province, China
| | - Yi Yu
- Department of Critical Care Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510006, Guangdong Province, China
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Feng J, Shan X, Wang L, Lu J, Cao Y, Yang L. Association of Body Iron Metabolism with Type 2 Diabetes Mellitus in Chinese Women of Childbearing Age: Results from the China Adult Chronic Disease and Nutrition Surveillance (2015). Nutrients 2023; 15:nu15081935. [PMID: 37111154 PMCID: PMC10141641 DOI: 10.3390/nu15081935] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/13/2023] [Accepted: 04/15/2023] [Indexed: 04/29/2023] Open
Abstract
High iron stores have been reported to be associated with type 2 diabetes mellitus (T2DM). However, evidence for the associations of iron metabolism with T2DM is inconsistent, and whether there is a threshold effect remains controversial. In the present study, we aimed to examine the associations between various iron biomarkers and the risk of T2DM as well as impaired glucose metabolism (IGM) and hyperglycemia in Chinese women of childbearing age. A total of 1145 women were divided into three groups (normal blood glucose metabolism group; IGM group; T2DM group). Biomarkers of iron metabolism (serum ferritin (SF), transferrin, soluble transferrin receptor (sTfR), transferrin saturation, serum iron, total body iron, and sTfR-to-lgferritin index) were measured. After adjusting for various confounding risk factors, SF and sTfR were positively associated with the risk of IGM (fourth vs. first quartile: SF odds ratio (OR) = 1.93 (95% CI 1.17-3.20) and sTfR OR = 3.08 (95% CI 1.84-5.14)) and T2DM (SF OR = 2.39 (95% CI 1.40-4.06) and sTfR OR = 3.84 (95% CI 2.53-5.83)). There was a nonlinear relationship between SF and risk of T2DM and hyperglycemia (p for nonlinearity < 0.01). Our findings suggested that SF and sTfR could be independent predictors of T2DM risk.
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Affiliation(s)
- Jie Feng
- Key Laboratory of Trace Element Nutrition of National Health Committee, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Xiaoyun Shan
- Key Laboratory of Trace Element Nutrition of National Health Committee, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
- Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 241001, China
| | - Lijuan Wang
- Key Laboratory of Trace Element Nutrition of National Health Committee, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Jiaxi Lu
- Key Laboratory of Trace Element Nutrition of National Health Committee, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Yang Cao
- Key Laboratory of Trace Element Nutrition of National Health Committee, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Lichen Yang
- Key Laboratory of Trace Element Nutrition of National Health Committee, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China
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Czempik PF, Wiórek A. Comparison of Standard and New Iron Status Biomarkers: A Prospective Cohort Study in Sepsis Patients. Healthcare (Basel) 2023; 11:healthcare11070995. [PMID: 37046922 PMCID: PMC10093794 DOI: 10.3390/healthcare11070995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 03/20/2023] [Accepted: 03/29/2023] [Indexed: 04/03/2023] Open
Abstract
Both iron deficiency (ID) and iron overload can have negative effects on the risk and course of infection. Therefore, the ability to accurately assess iron status in these patients is of the utmost importance. Systemic inflammation in sepsis patients affects the results of standard iron biomarkers and makes accurate diagnosis of ID problematic. The aim of our study was to analyze the association between widely available standard iron biomarkers and selected new iron biomarkers in various iron status subgroups among sepsis patients. Consecutive patients diagnosed with sepsis or septic shock and procalcitonin concentration > 0.5 ng/mL were enrolled. The following iron biomarkers were determined: iron, ferritin, transferrin, transferrin saturation, reticulocyte (Ret) number and percentage, Ret hemoglobin equivalent, Ret fluorescence subpopulations, and hepcidin concentration. The study group comprised 90 study subjects. There were 42 (47%) patients with normal iron status, 6 (6%) with ID without anemia, and 42 (47%) with ID anemia. No meaningful correlation exists between standard and new iron biomarkers in various iron status subgroups among sepsis patients. Therefore, standard iron biomarkers cannot be used to diagnose ID in this cohort.
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Affiliation(s)
- Piotr F. Czempik
- Department of Anaesthesiology and Intensive Care, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland
- Transfusion Committee, University Clinical Centre of Medical University of Silesia, 40-055 Katowice, Poland
- Correspondence: ; Tel.: +48-32-7894201
| | - Agnieszka Wiórek
- Department of Anaesthesiology and Intensive Care, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland
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10
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The role of iron in chronic inflammatory diseases: from mechanisms to treatment options in anemia of inflammation. Blood 2022; 140:2011-2023. [PMID: 35994752 DOI: 10.1182/blood.2021013472] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 08/09/2022] [Indexed: 11/20/2022] Open
Abstract
Anemia of inflammation (AI) is a highly prevalent comorbidity in patients affected by chronic inflammatory disorders, such as chronic kidney disease, inflammatory bowel disease, or cancer, that negatively affect disease outcome and quality of life. The pathophysiology of AI is multifactorial, with inflammatory hypoferremia and iron-restricted erythropoiesis playing a major role in the context of disease-specific factors. Here, we review the recent progress in our understanding of the molecular mechanisms contributing to iron dysregulation in AI, the impact of hypoferremia and anemia on the course of the underlying disease, and (novel) therapeutic strategies applied to treat AI.
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11
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Abstract
PURPOSE OF REVIEW Red blood cell (RBC) clearance has been studied for decades in many different pathologies, which has revealed different routes of RBC degradation, depending on the situation. This review summarizes the latest mechanistic insights on RBC clearance in different contexts; during homeostatic removal, immune-mediated destruction, and systemic inflammation. RECENT FINDINGS Besides the recognition of a variety of potential 'eat me' signals on RBCs, recent evidence suggests that normal RBC degradation is driven by the increase of the adhesive properties of RBCs, mediating the retention in the spleen and leading to RBC hemolysis. Furthermore, immune-mediated degradation of RBCs seems to be fine-tuned by the balance between the density of the antigens expressed on RBCs and the presence of 'don't eat me' signals. Moreover, besides RBC clearance by macrophages, neutrophils seem to play a much more prominent role in immune-mediated RBC removal than anticipated. Lastly, RBC clearance during systemic inflammation appears to be driven by a combination of extreme macrophage activity in response to proinflammatory cytokines as well as direct damage of RBC by the inflammation or inflammatory agent. SUMMARY Recent studies on RBC clearance have expanded our knowledge on their destruction in different contexts.
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Affiliation(s)
- Silvia Neri
- Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam
| | - Dorine W Swinkels
- Translational Metabolic Laboratory, Department of Laboratory Medicine, RadboudUMC, Nijmegen, The Netherlands
| | - Hanke L Matlung
- Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam
| | - Robin van Bruggen
- Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, University of Amsterdam, Amsterdam
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12
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Hattori S, Matono T, Hirakawa M, Nakamata Y, Okamura K, Hamashoji T, Kometani T, Nakashima T, Sasaki S, Minagawa R, Kajiyama K. Critical peritonitis secondary to gastrointestinal mucormycosis in a peritoneal dialysis patient: a case report. CEN Case Rep 2021; 11:31-35. [PMID: 34273082 DOI: 10.1007/s13730-021-00628-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 07/12/2021] [Indexed: 11/24/2022] Open
Abstract
Immunodeficient patients are susceptible to systemic fungal infections; however, these rarely cause secondary peritonitis. A 66-year-old man with multiple myeloma and diabetes mellitus on continuous ambulatory peritoneal dialysis (CAPD) presented with cloudy ascitic fluid. He had been treated with corticosteroids for 1 month for Tolosa-Hunt syndrome. We diagnosed peritoneal dialysis-related peritonitis caused by Enterococcus avium, removed the CAPD catheter, and initiated intravenous ampicillin. Computed tomography (CT) revealed an intramural gastric mass and a thinning ascending colon wall. Four days later, follow-up contrast-enhanced CT showed penetration of the ascending colon and rupture of the ileocolic artery. Emergency open surgery revealed hemorrhagic infarction with mucormycosis. We initiated intravenous liposomal amphotericin B 20 days after admission; however, he died 55 days later. Anatomical abnormalities, such as gastrointestinal perforation, should be considered for peritonitis in immunodeficient patients. Gastrointestinal mucormycosis is rare but fatal, resulting from a delay in diagnosis and consequent gastrointestinal perforation. For an early diagnosis and a favorable clinical outcome, it is important to consider the risk factors for mucormycosis, including corticosteroid use, diabetes, end-stage kidney diseases.
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Affiliation(s)
- Soken Hattori
- Department of Nephrology, Aso Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka, 820-8505, Japan.
| | - Takashi Matono
- Department of Infectious Diseases, Aso Iizuka Hospital, Iizuka, Japan
| | - Makoto Hirakawa
- Department of Nephrology, Aso Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka, 820-8505, Japan
| | - Yusuke Nakamata
- Department of Nephrology, Aso Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka, 820-8505, Japan
| | - Kazuhiro Okamura
- Department of Nephrology, Aso Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka, 820-8505, Japan
| | - Tomoya Hamashoji
- Department of Nephrology, Aso Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka, 820-8505, Japan
| | - Takuro Kometani
- Department of Nephrology, Aso Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka, 820-8505, Japan
| | - Takafumi Nakashima
- Department of Nephrology, Aso Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka, 820-8505, Japan
| | - Sho Sasaki
- Department of Nephrology, Aso Iizuka Hospital, 3-83 Yoshio-machi, Iizuka, Fukuoka, 820-8505, Japan
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Forceville X, Van Antwerpen P, Preiser JC. Selenocompounds and Sepsis: Redox Bypass Hypothesis for Early Diagnosis and Treatment: Part A-Early Acute Phase of Sepsis: An Extraordinary Redox Situation (Leukocyte/Endothelium Interaction Leading to Endothelial Damage). Antioxid Redox Signal 2021; 35:113-138. [PMID: 33567962 DOI: 10.1089/ars.2020.8063] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Significance: Sepsis is a health disaster. In sepsis, an initial, beneficial local immune response against infection evolves rapidly into a generalized, dysregulated response or a state of chaos, leading to multiple organ failure. Use of life-sustaining supportive therapies creates an unnatural condition, enabling the complex cascades of the sepsis response to develop in patients who would otherwise die. Multiple attempts to control sepsis at an early stage have been unsuccessful. Recent Advances: Major events in early sepsis include activation and binding of leukocytes and endothelial cells in the microcirculation, damage of the endothelial surface layer (ESL), and a decrease in the plasma concentration of the antioxidant enzyme, selenoprotein-P. These events induce an increase in intracellular redox potential and lymphocyte apoptosis, whereas apoptosis is delayed in monocytes and neutrophils. They also induce endothelial mitochondrial and cell damage. Critical Issues: Neutrophil production increases dramatically, and aggressive immature forms are released. Leukocyte cross talk with other leukocytes and with damaged endothelial cells amplifies the inflammatory response. The release of large quantities of reactive oxygen, halogen, and nitrogen species as a result of the leukocyte respiratory burst, endothelial mitochondrial damage, and ischemia/reperfusion processes, along with the marked decrease in selenoprotein-P concentrations, leads to peroxynitrite damage of the ESL, reducing flow and damaging the endothelial barrier. Future Directions: Endothelial barrier damage by activated leukocytes is a time-sensitive event in sepsis, occurring within hours and representing the first step toward organ failure and death. Reducing or stopping this event is necessary before irreversible damage occurs.
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Affiliation(s)
- Xavier Forceville
- Medico-Surgical Intensive Care Unit, Great Hospital of East Francilien-Meaux Site, Hôpital Saint Faron, Meaux, France.,Clinical Investigation Center (CIC Inserm 1414), CHU de Rennes, Université de Rennes 1, Rennes, France
| | - Pierre Van Antwerpen
- Pharmacognosy, Bioanalysis and Drug Discovery and Analytical Platform of the Faculty of Pharmacy, Université libre de Bruxelles (ULB), Bruxelles, Belgium
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Sanyear C, Chiawtada B, Butthep P, Svasti S, Fucharoen S, Masaratana P. The hypoferremic response to acute inflammation is maintained in thalassemia mice even under parenteral iron loading. PeerJ 2021; 9:e11367. [PMID: 33987030 PMCID: PMC8092106 DOI: 10.7717/peerj.11367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 04/07/2021] [Indexed: 11/20/2022] Open
Abstract
Background Hepcidin controls iron homeostasis by inducing the degradation of the iron efflux protein, ferroportin (FPN1), and subsequently reducing serum iron levels. Hepcidin expression is influenced by multiple factors, including iron stores, ineffective erythropoiesis, and inflammation. However, the interactions between these factors under thalassemic condition remain unclear. This study aimed to determine the hypoferremic and transcriptional responses of iron homeostasis to acute inflammatory induction by lipopolysaccharide (LPS) in thalassemic (Hbbth3/+) mice with/without parenteral iron loading with iron dextran. Methods Wild type and Hbbth3/+ mice were intramuscularly injected with 5 mg of iron dextran once daily for two consecutive days. After a 2-week equilibration, acute inflammation was induced by an intraperitoneal injection of a single dose of 1 µg/g body weight of LPS. Control groups for both iron loading and acute inflammation received equal volume(s) of saline solution. Blood and tissue samples were collected at 6 hours after LPS (or saline) injection. Iron parameters and mRNA expression of hepcidin as well as genes involved in iron transport and metabolism in wild type and Hbbth3/+ mice were analyzed and compared by Kruskal–Wallis test with pairwise Mann–Whitney U test. Results We found the inductive effects of LPS on liver IL-6 mRNA expression to be more pronounced under parenteral iron loading. Upon LPS administration, splenic erythroferrone (ERFE) mRNA levels were reduced only in iron-treated mice, whereas, liver bone morphogenetic protein 6 (BMP6) mRNA levels were decreased under both control and parenteral iron loading conditions. Despite the altered expression of the aforementioned hepcidin regulators, the stimulatory effect of LPS on hepcidin mRNA expression was blunt in iron-treated Hbbth3/+ mice. Contrary to the blunted hepcidin response, LPS treatment suppressed FPN1 mRNA expression in the liver, spleen, and duodenum, as well as reduced serum iron levels of Hbbth3/+ mice with parenteral iron loading. Conclusion Our study suggests that a hypoferremic response to LPS-induced acute inflammation is maintained in thalassemic mice with parenteral iron loading in a hepcidin-independent manner.
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Affiliation(s)
- Chanita Sanyear
- Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.,Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
| | - Buraporn Chiawtada
- Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Punnee Butthep
- Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Saovaros Svasti
- Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
| | - Suthat Fucharoen
- Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
| | - Patarabutr Masaratana
- Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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15
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El-Mallah CA, Beyh YS, Obeid OA. Iron Fortification and Supplementation: Fighting Anemia of Chronic Diseases or Fueling Obesity? Curr Dev Nutr 2021; 5:nzab032. [PMID: 33959691 PMCID: PMC8085477 DOI: 10.1093/cdn/nzab032] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 01/07/2021] [Accepted: 03/31/2021] [Indexed: 12/13/2022] Open
Abstract
The significant worldwide increase in obesity has become a major health problem. Excess adiposity has been extensively linked to inflammation. Recently, studies have shown that dietary intake and microbiota dysbiosis can affect the health of the gut and lead to low-grade systemic inflammation, worsening the state of obesity and further exacerbating inflammation. The latter is shown to decrease iron status and potentially increase the risk of anemia by inhibiting iron absorption. Hence, anemia of obesity is independent of iron intake and does not properly respond to increased iron ingestion. Therefore, countries with a high rate of obesity should assess the health impact of fortification and supplementation with iron due to their potential drawbacks. This review tries to elucidate the relation between inflammation and iron status to better understand the etiology of anemia of obesity and chronic diseases and wisely design any dietary or medical interventions for the management of anemia and/or obesity.
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Affiliation(s)
- Carla A El-Mallah
- Department of Nutrition and Food Science, Faculty of Agricultural and Food Sciences, American University of Beirut, Beirut, Lebanon
| | - Yara S Beyh
- Nutrition and Health Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA
| | - Omar A Obeid
- Department of Nutrition and Food Science, Faculty of Agricultural and Food Sciences, American University of Beirut, Beirut, Lebanon
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Liu Q, Wu J, Zhang X, Wu X, Zhao Y, Ren J. Iron homeostasis and disorders revisited in the sepsis. Free Radic Biol Med 2021; 165:1-13. [PMID: 33486088 DOI: 10.1016/j.freeradbiomed.2021.01.025] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 12/31/2020] [Accepted: 01/11/2021] [Indexed: 12/26/2022]
Abstract
Sepsis is a life-threatening condition caused by a dysregulated host-response to inflammation, although it currently lacks a fully elucidated pathobiology. Iron is a crucial trace element that is essential for fundamental processes in both humans and bacteria. During sepsis, iron metabolism is altered, including increased iron transport and uptake into cells and decreased iron export. The intracellular sequestration of iron limits its availability to circulating pathogens, which serves as a conservative strategy against the pathogens. Although iron retention has been showed to have protective protect effects, an increase in labile iron may cause oxidative injury and cell death (e.g., pyroptosis, ferroptosis) as the condition progresses. Moreover, iron disorders are substantial and correlate with the severity of sepsis. This also suggests that iron may be useful as a diagnostic marker for evaluating the severity and predicting the outcome of the disease. Further knowledge about these disorders could help in evaluating how drugs targeting iron homeostasis can be optimally applied to improve the treatment of patients with sepsis. Here, we present a comprehensive review of recent advances in the understanding of iron metabolism, focusing on the regulatory mechanisms and iron-mediated injury in sepsis.
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Affiliation(s)
- Qinjie Liu
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, PR China.
| | - Jie Wu
- Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, 210002, PR China.
| | - Xufei Zhang
- Research Institute of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, PR China.
| | - Xiuwen Wu
- Research Institute of General Surgery, Jinling Hospital, Nanjing, 210002, PR China.
| | - Yun Zhao
- Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, 210002, PR China.
| | - Jianan Ren
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, PR China; Department of General Surgery, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, 210002, PR China; Research Institute of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, PR China.
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Carbajal-Guerrero J, Gacto-Sanchez P, Mendoza-Prieto M, Cayuela-Dominguez A, Manuel Lopez-Chozas J. Role Of Intravenous Iron Over Nonsurgical Transfusions In Major Burns. ANNALS OF BURNS AND FIRE DISASTERS 2020; 33:299-303. [PMID: 33708019 PMCID: PMC7894841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 06/24/2020] [Indexed: 06/12/2023]
Abstract
Anemia is a frequent condition in burn patients due to a mixture of blood loss and chronic inflammation. Transfusions increase the probability of serious infections and reduce overall survival, especially when unrelated to perioperative blood loss. Once the surgical phase in burn patients is completed, the role of parenteral iron administration in the reduction of subsequent transfusions is not well established. Burn patients subjected to at least two surgeries and presenting progressive anemia after concluding the surgical phase, without major symptoms, were selected (n=12). Those patients with confirmed iron deficiency were treated with intravenous (i.v.) ferric carboxymaltose (n=8). Subsequently, these patients were compared with a group of 18 control patients selected from our historical database (n=1375), matching controls by age (±5 years), sex, and TBSA burn (±6%). The objective was to verify if i.v. iron administration reduced the need for blood transfusions after the surgical phase. The analysis concluded that none of the cases treated required transfusions compared to 44% of the controls. There were no side effects related to the i.v. iron infusion. This result suggests that i.v. iron supplementation with ferric carboxymaltose could be an alternative in anemic patients without major symptoms once the surgical phase is completed. Iron deficiency should be assessed and i.v. supplementation must be administered if required in burn patients showing progressive anemia.
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18
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Nairz M, Weiss G. Iron in infection and immunity. Mol Aspects Med 2020; 75:100864. [PMID: 32461004 DOI: 10.1016/j.mam.2020.100864] [Citation(s) in RCA: 199] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 04/25/2020] [Accepted: 05/05/2020] [Indexed: 12/12/2022]
Abstract
Iron is an essential micronutrient for virtually all living cells. In infectious diseases, both invading pathogens and mammalian cells including those of the immune system require iron to sustain their function, metabolism and proliferation. On the one hand, microbial iron uptake is linked to the virulence of most human pathogens. On the other hand, the sequestration of iron from bacteria and other microorganisms is an efficient strategy of host defense in line with the principles of 'nutritional immunity'. In an acute infection, host-driven iron withdrawal inhibits the growth of pathogens. Chronic immune activation due to persistent infection, autoimmune disease or malignancy however, sequesters iron not only from infectious agents, autoreactive lymphocytes and neoplastic cells but also from erythroid progenitors. This is one of the key mechanisms which collectively result in the anemia of chronic inflammation. In this review, we highlight the most important interconnections between iron metabolism and immunity, focusing on host defense against relevant infections and on the clinical consequences of anemia of inflammation.
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Affiliation(s)
- Manfred Nairz
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Austria
| | - Günter Weiss
- Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University of Innsbruck, Austria; Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Austria.
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Brandtner A, Tymoszuk P, Nairz M, Lehner GF, Fritsche G, Vales A, Falkner A, Schennach H, Theurl I, Joannidis M, Weiss G, Pfeifhofer-Obermair C. Linkage of alterations in systemic iron homeostasis to patients' outcome in sepsis: a prospective study. J Intensive Care 2020; 8:76. [PMID: 33014378 PMCID: PMC7528491 DOI: 10.1186/s40560-020-00495-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 09/22/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Sepsis, a dysregulated host response following infection, is associated with massive immune activation and high mortality rates. There is still a need to define further risk factors and laboratory parameters predicting the clinical course. Iron metabolism is regulated by both, the body's iron status and the immune response. Iron itself is required for erythropoiesis but also for many cellular and metabolic functions. Moreover, iron availability is a critical determinant in infections because it is an essential nutrient for most microbes but also impacts on immune function and intravascular oxidative stress. Herein, we used a prospective study design to investigate the putative impact of serum iron parameters on the outcome of sepsis. METHODS Serum markers of iron metabolism were measured in a prospective cohort of 61 patients (37 males, 24 females) with sepsis defined by Sepsis-3 criteria in a medical intensive care unit (ICU) and compared between survivors and non-survivors. Regulation of iron parameters in patients stratified by focus of infection and co-medication as well as association of the markers with sepsis severity scores and survival were investigated with linear and logistic regression corrected for sex and age effects. RESULTS Positive correlations of increased serum iron and ferritin concentrations upon ICU admission with the severity of organ failure (SOFA score) and with mortality were observed. Moreover, high TF-Sat, elevated ferritin and serum iron levels and low transferrin concentrations were associated with reduced survival. A logistic regression model consisting of SOFA and transferrin saturation (SOFA-TF-Sat) had the best predictive power for survival in septic ICU patients. Of note, administration of blood transfusions prior to ICU admission resulted in increased TF-Sat and reduced survival of septic patients. CONCLUSIONS Our study could show an important impact of serum iron parameters on the outcome of sepsis. Furthermore, we identified transferrin saturation as a stand-alone predictor of sepsis survival and as a parameter of iron metabolism which may in a combined model improve the prediction power of the SOFA score. TRIAL REGISTRATION The study was carried out in accordance with the recommendations of the Declaration of Helsinki on biomedical research. The study was approved by the institutional ethics review board of the Medical University Innsbruck (study AN2013-0006).
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Affiliation(s)
- Anna Brandtner
- Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Piotr Tymoszuk
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck, Austria
| | - Manfred Nairz
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck, Austria
| | - Georg F. Lehner
- Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Gernot Fritsche
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck, Austria
| | - Anja Vales
- Central Institute for Blood Transfusion and Immunology, Innsbruck, Austria
| | - Andreas Falkner
- Central Institute for Blood Transfusion and Immunology, Innsbruck, Austria
| | - Harald Schennach
- Central Institute for Blood Transfusion and Immunology, Innsbruck, Austria
| | - Igor Theurl
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck, Austria
| | - Michael Joannidis
- Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria
| | - Günter Weiss
- Department of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck, Austria
- Christian Doppler Laboratory for Iron Metabolism and Anemia Research, Medical University of Innsbruck, Innsbruck, Austria
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20
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Hedayati S, Nachvak SM, Samadi M, Motamedi-Motlagh A, Moradi S. Malnutrition and nutritional status in critically ill patients with enteral nutrition. MEDITERRANEAN JOURNAL OF NUTRITION AND METABOLISM 2020. [DOI: 10.3233/mnm-200421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND & OBJECTIVE: The prevention of malnutrition is an important factor in the survival of critically ill patients with enteral nutrition. The present study aims to assess the nutritional status and its association with some blood-related markers in critically ill patients with enteral nutrition during hospitalization in the intensive care units (ICUs). METHODS: Totally, 110 patients participated in this study from the time of admission to discharge at five ICUs. The patients’ nutritional status was assessed by subjective global assessment (SGA), Acute Physiology and Chronic Health Evaluation and Albumin, Total Iron Binding Capacity (TIBC), Hemoglobin (Hb), Hematocrit (HCT), Ferritin, and Feas biochemical indices and anthropometric parameters. RESULTS: Malnutrition prevalence increased significantly on the day of discharge (83.6%) compared to the day of admission (41.8%), according to SGA (P < 0.001). Hb, HCT, serum Fe decreased and ferritin, also TIBC were increased during hospitalization in ICU. The malnutrition risk predictors based on the logistic regression were low levels of Hb (OR = 0.6), HCT (OR = 0.9), Fe (OR = 0.9), Albumin (OR = 0.3) and High Ferritin level (OR = 1.006) on the admission day. Anemia of inflammation (AI) was observed during ICU stay. CONCLUSION: This study demonstrated that malnutrition is an increasing phenomenon in the ICU patients and the delay in patient’s enteral feeding had a direct influence in the prevalence of malnutrition on discharge day.
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Affiliation(s)
- Safoora Hedayati
- Department of Nutrition, School of Nutrition Science and Food Technology, Committee of the Deputy of Research and Technology of Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Seyyed Mostafa Nachvak
- Department of Nutritional Sciences, Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mehnoosh Samadi
- Department of Nutritional Sciences, Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | | | - Shima Moradi
- Department of Nutritional Sciences, Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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21
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Boshuizen M, Binnekade JM, Nota B, van de Groep K, Cremer OL, Horn J, Schultz MJ, van Bruggen R, Juffermans NP. Potential of Parameters of Iron Metabolism for the Diagnosis of Anemia of Inflammation in the Critically Ill. Transfus Med Hemother 2020; 47:61-67. [PMID: 32110195 PMCID: PMC7036579 DOI: 10.1159/000497123] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 01/21/2019] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Anemia of inflammation (AI) is the most common cause of anemia in the critically ill, but its diagnosis is a challenge. New therapies specific to AI are in development, and they require accurate detection of AI. This study explores the potential of parameters of iron metabolism for the diagnosis of AI during an ICU stay. METHODS In a nested case-control study, 30 patients developing AI were matched to 60 controls. The iron parameters were determined in plasma samples during an ICU stay. Receiver operating characteristic curves were used to determine the iron parameter threshold with the highest sensitivity and specificity to predict AI. Likelihood ratios as well as positive and negative predictive values were calculated as well. RESULTS The sensitivity of iron parameters for diagnosing AI ranges between 62 and 76%, and the specificity between 57 and 72%. Iron and transferrin show the greatest area under the curve. Iron shows the highest sensitivity, and transferrin and transferrin saturation display the highest specificity. Hepcidin and ferritin show the lowest specificity. At an actual anemia prevalence of 53%, the diagnostic accuracy of iron, transferrin, and transferrin saturation was fair, with a positive predictive value between 71 and 73%. Combining iron, transferrin, transferrin saturation, hepcidin, and/or ferritin levels did not increase the accuracy of the AI diagnosis. CONCLUSIONS In this explorative study on the use of different parameters of iron metabolism for diagnosing AI during an ICU stay, low levels of commonly measured markers such as plasma iron, transferrin, and transferrin saturation have the highest sensitivity and specificity and outperform ferritin and hepcidin.
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Affiliation(s)
- Margit Boshuizen
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Jan M. Binnekade
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Benjamin Nota
- Department of Research Facilities, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Kirsten van de Groep
- Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Olaf L. Cremer
- Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Janneke Horn
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Marcus J. Schultz
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Mahidol Oxford Tropical Medicine Research Unit (MORU), Bangkok, Thailand
| | - Robin van Bruggen
- Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Nicole P. Juffermans
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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22
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Napolitano LM. Understanding Anemia in the ICU to Develop Future Treatment Strategies. Am J Respir Crit Care Med 2019; 198:554-555. [PMID: 29944840 DOI: 10.1164/rccm.201805-0989ed] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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23
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Jiang Y, Jiang FQ, Kong F, An MM, Jin BB, Cao D, Gong P. Inflammatory anemia-associated parameters are related to 28-day mortality in patients with sepsis admitted to the ICU: a preliminary observational study. Ann Intensive Care 2019; 9:67. [PMID: 31183575 PMCID: PMC6557959 DOI: 10.1186/s13613-019-0542-7] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Accepted: 05/31/2019] [Indexed: 12/26/2022] Open
Abstract
Background Anemia is one of the most common complications of sepsis. Sepsis-related anemia is associated mainly with inflammation. We aimed to observe the changes in the inflammatory anemia-associated parameters of patients with sepsis in the early stage of intensive care unit (ICU) admission and to evaluate their association with 28-day mortality. Methods A total of 198 patients with sepsis were divided into survivor (n = 110) and non-survivor (n = 88) groups on the basis of 28-day survival. Healthy volunteers (n = 20) were enrolled as a control group. Plasma levels of iron, ferritin, erythropoietin (EPO), soluble transferrin receptor (sTfR), hepcidin, interleukin-6 (IL-6), hemoglobin and the red blood cell distribution width (RDW) were measured on days 1, 3 and 7 of ICU admission. Clinical data and laboratory findings were collected, and the Sequential Organ Failure Assessment (SOFA) score was calculated. Results Patients with sepsis showed significant decreases in hemoglobin, plasma iron and sTfR/log ferritin and significant increases in plasma EPO, sTfR, hepcidin, ferritin and IL-6 on days 1, 3 and 7 of ICU admission compared with healthy volunteers. Hemoglobin was correlated negatively with plasma IL-6 and hepcidin. In patients with sepsis, non-survivors had significantly lower plasma iron, EPO and sTfR/log ferritin, but higher plasma hepcidin, ferritin and IL-6 than survivors on days 1, 3 and 7 of ICU admission. Plasma EPO, hepcidin, ferritin, IL-6, sTfR/log ferritin, the RDW and SOFA score were associated significantly with 28-day mortality but to a varying extent. In particular, in predicting 28-day mortality, plasma hepcidin had an area under the receiver operating curve of 0.808 and 87.3% specificity, which was the highest among the inflammatory anemia-associated parameters tested. Conclusions Inflammatory anemia-associated parameters changed significantly in patients with sepsis in the first week of ICU admission. Plasma EPO, hepcidin, ferritin, IL-6, sTfR/log ferritin, the RDW and SOFA score were associated significantly with 28-day mortality. Plasma hepcidin might have a superior predictive value, with high specificity, compared with other inflammatory anemia-associated parameters for 28-day mortality of sepsis patients in the ICU. Electronic supplementary material The online version of this article (10.1186/s13613-019-0542-7) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yi Jiang
- Department of Emergency Medicine, General Hospital of Tianjin Medical University, Tianjin City, China
| | - Feng-Quan Jiang
- Department of Clinical Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian City, Liaoning Province, China
| | - Fang Kong
- Department of Critical Care Medicine, Huizhou Municipal Central Hospital, Huizhou City, Guangzhou Province, China
| | - Meng-Meng An
- Department of Emergency Medicine, First Affiliated Hospital of Dalian Medical University, Dalian City, Liaoning Province, China
| | - Bei-Bei Jin
- Department of Emergency Medicine, First Affiliated Hospital of Dalian Medical University, Dalian City, Liaoning Province, China
| | - Da Cao
- Department of Emergency Medicine, First Affiliated Hospital of Dalian Medical University, Dalian City, Liaoning Province, China
| | - Ping Gong
- Department of Emergency Medicine, First Affiliated Hospital of Dalian Medical University, Dalian City, Liaoning Province, China.
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24
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Boshuizen M, van Hezel ME, van Manen L, Straat M, Somsen YBO, Spoelstra-de Man AME, Blumberg N, van Bruggen R, Juffermans NP. The effect of red blood cell transfusion on iron metabolism in critically ill patients. Transfusion 2018; 59:1196-1201. [PMID: 30597563 DOI: 10.1111/trf.15127] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Revised: 10/28/2018] [Accepted: 10/28/2018] [Indexed: 01/26/2023]
Abstract
BACKGROUND Anemia of inflammation (AI) has a high prevalence in critically ill patients. In AI, iron metabolism is altered, as high levels of inflammation-induced hepcidin reduce the amount of iron available for erythropoiesis. AI is treated with red blood cell (RBC) transfusions. The effect of RBC transfusion on iron metabolism during inflammatory processes in adults is unknown. We investigated the effect of RBC transfusion on iron metabolism in critically ill patients. METHODS In a prospective cohort study in 61 critically ill patients who received 1 RBC unit, levels of iron variables were determined before, directly after, and 24 hours after transfusion in septic and nonseptic patients. RESULTS Serum iron levels were low and increased after transfusion (p = 0.02). However, RBC transfusion had no effect on transferrin saturation (p = 0.14) and ferritin levels (p = 0.74). Hepcidin levels increased after RBC transfusion (p = 0.01), while interleukin-6 levels decreased (p = 0.03). In septic patients, RBC transfusion induced a decrease in haptoglobin levels compared to baseline, which did not occur in nonseptic patients (p = 0.01). The effect of RBC transfusion on other iron variables did not differ between septic and nonseptic patients. CONCLUSION Transfusion of a RBC unit transiently increases serum iron levels in intensive care unit patients. The increase in hepcidin levels after transfusion can further decrease iron release from intracellular storage making it available for erythropoiesis. RBC transfusion is associated with a decrease in haptoglobin levels in septic compared to nonseptic patients, but did not affect other markers of hemolysis.
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Affiliation(s)
- Margit Boshuizen
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.,Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Maike E van Hezel
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.,Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Lisa van Manen
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.,Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Marleen Straat
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Yvemarie B O Somsen
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | | | - Neil Blumberg
- Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, New York
| | - Robin van Bruggen
- Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Nicole P Juffermans
- Department of Intensive Care Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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25
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Swenson ER, Porcher R, Piagnerelli M. Iron deficiency and infection: another pathway to explore in critically ill patients? Intensive Care Med 2018; 44:2260-2262. [PMID: 30397782 DOI: 10.1007/s00134-018-5438-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Accepted: 10/25/2018] [Indexed: 12/23/2022]
Affiliation(s)
- Erik R Swenson
- Pulmonary, Critical Care and Sleep Medicine, University of Washington, VA Puget Sound Health Care System, Seattle, WA, 98108, USA
| | - Raphaël Porcher
- Centre d'Epidémiologie Clinique, Hôtel-Dieu, AP-HP, Centre de Recherche Epidémiologie et Statistique, Inserm U1153, Université Paris Descartes, 75004, Paris, France
| | - Michaël Piagnerelli
- Intensive Care, CHU-Charleroi Marie Curie, Experimental Medicine Laboratory, Université Libre de Bruxelles, 6042, Charleroi, Belgium.
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