Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management

Cappellini, Maria Domenica; Comín‐Colet, Josep; Francisco, Angel de; Dignaß, Axel; Doehner, Wolfram; Lam, Carolyn S.P.; Macdougall, Iain C.; Rogler, Gerhard; Camaschella, Clara; Kadir, Rezan A.; Kassebaum, Nicholas J; Spahn, Donat R.; Taher, Alì; Musallam, Khaled M.

doi:10.1002/ajh.24820

Cited by 322 publications

(411 citation statements)

References 111 publications

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“…These proportions are similar to those in a previous report from Turkey . Among children who are in an inflammatory period of chronic disease, the reported incidence of iron deficiency can range from 13% to 90% . We observed a higher prevalence of AID than FID among children with FMF.…”

Section: Discussionsupporting

confidence: 90%

“…Iron deficiency is a very common but often overlooked condition, especially in patients with chronic inflammatory conditions . However, there is uncertainty among physicians regarding how to diagnose this deficiency in patients with chronic inflammatory illnesses because two different forms occur (FID and AID), depending on iron body stores and utility.…”

Section: Discussionmentioning

confidence: 99%

“…Clinicians need to be able to recognize iron deficiency before iron deficiency anemia (IDA) develops in these patients. Functional iron deficiency (FID) is a major component of anemia of chronic disease and occurs in subjects with infection, inflammation, and malignancy . This form of deficiency occurs when there is insufficient iron transport into erythroid precursors despite sufficient body stores of iron during inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Utility of new red cell parameters for distinguishing functional iron deficiency from absolute iron deficiency in children with familial Mediterranean fever

Yıldırım

Kaya

Bakkaloğlu

2019

Int J Lab Hematology

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Introduction Few data are available on the clinical utility of new red cell parameters for detecting anemia in children with inflammatory diseases. The aim was to investigate the utility of three new red cell parameters for distinguishing functional iron deficiency (FID) from absolute iron deficiency (AID) in children with familial Mediterranean fever (FMF). Methods The study involved 198 children with genetically confirmed FMF and 18 healthy‐age and sex‐matched controls. Complete blood counts with the new red cell parameters of low hemoglobin (Hb) density (LHD), microcytic anemia factor (MAF), and red blood cell size factor (RSF) were measured in a Unicel® DxH800, along with conventional iron parameters. The FMF patients’ medical records were retrospectively reviewed to assess inflammation status and genetic results. Results The frequencies of FID and AID among the 198 FMF patients were 35% and 65%, respectively. Among patients with homozygous MEFV mutation, FID was more common than AID (P < 0.05). Mean LHD was significantly higher and mean Hb, MCV, MAF, and RSF were significantly lower among the FMF patients with FID compared to those with AID and controls (P < 0.05). Specificity for distinguishing FID from AID in children with FMF was greatest for MAF (92%; 95% confidence interval [CI] 85%‐96%), followed by LHD (85%; 95% CI 76%‐91%) and RSF (81%; 95% CI 72%‐88%). Conclusion The new red cell parameters measured by the Unicel® DxH800 may be useful for guiding physicians in distinguishing FID from AID in children with FMF.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Utility of new red cell parameters for distinguishing functional iron deficiency from absolute iron deficiency in children with familial Mediterranean fever

Yıldırım

Kaya

Bakkaloğlu

2019

Int J Lab Hematology

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“…The laboratory criteria used to define iron deficiency and provide indication for treatment are different in CKD compared to normal renal function [30]. In CKD, absolute iron deficiency is likely to be present when the TSAT is ≤20% and the serum ferritin concentration is ≤100 ng/mL among predialysis and peritoneal dialysis (PD) patients or ≤200 ng/mL among patients undergoing hemodialysis.…”

Section: Definitions and Diagnosis Of Iron Deficiency In Ckd Patientsmentioning

confidence: 99%

“…Functional iron deficiency, both ESA-induced functional deficiency and anemia of chronic disease are usually characterized by TSAT ≤20% and elevated ferritin levels (as high as 800 ng/mL) [29, 30]. …”

Section: Definitions and Diagnosis Of Iron Deficiency In Ckd Patientsmentioning

confidence: 99%

Iron Deficiency Anemia in Chronic Kidney Disease

2019

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Iron deficiency anemia is a common complication of chronic kidney disease (CKD). CKD patients suffer from both absolute and functional iron deficiency. Absolute iron deficiency is defined by severely reduced or absent iron stores, while functional iron deficiency is defined by adequate iron stores but insufficient iron availability for incorporation into erythroid precursors. This is due to increased levels of hepcidin. Anemia in CKD is associated with an increased risk of morbidity and mortality. The association between anemia and mortality may be related to the severity of anemia. All CKD patients should be screened for anemia during the initial evaluation for CKD. Criteria used to define iron deficiency are different among CKD compared to normal renal function. Among CKD patients, absolute iron deficiency is defined when the transferrin saturation (TSAT) is ≤20% and the serum ferritin concentration is ≤100 ng/mL among predialysis and peritoneal dialysis patients or ≤200 ng/mL among hemodialysis patients. Functional iron deficiency, also known as iron-restricted erythropoiesis, is characterized by TSAT ≤20% and elevated ferritin levels. Iron supplementation is recommended for all CKD patients with anemia. There is general agreement according to guidelines that intravenous (i.v.) iron supplementation is the preferred method for CKD patients on dialysis (CKD stage 5D) and either i.v. or oral iron is recommended for patients with CKD ND (CKD stages 3–5). In this review we discuss the evidence base for these recommendations.

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Association of Maternal and Child Anemia With Brain Structure in Early Life in South Africa

et al. 2022

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ImportanceAnemia affects millions of pregnant women and their children worldwide, particularly in low- and middle-income countries. Although anemia in pregnancy is a well-described risk factor for cognitive development, the association with child brain structure is poorly understood.ObjectiveTo explore the association of anemia during pregnancy and postnatal child anemia with brain structure in early life.Design, Setting, and ParticipantsThis neuroimaging nested cohort study was embedded within the Drakenstein Child Health Study (DCHS), a population-based birth cohort in South Africa. Pregnant individuals were enrolled into the DCHS between 2012 and 2015 from 2 clinics in a periurban setting. Mother-child pairs were assessed prospectively; follow-up is ongoing. A subgroup of children had brain magnetic resonance imaging (MRI) at age 2 to 3 years from 2015 to 2018. This study focused on the 147 pairs with structural neuroimaging and available hemoglobin data. Data analyses were conducted in 2021 and 2022.ExposuresMothers had hemoglobin measurements during pregnancy, and a subgroup of children had hemoglobin measurements during early life. Anemia was classified as hemoglobin levels less than 11 g/dL based on World Health Organization guidelines; children younger than 6 months were classified using local guidelines.Main Outcomes and MeasuresChild brain volumes of global, subcortical, and corpus callosum structures were quantified using T1-weighted MRI. Linear regression models were used to analyze the associations between maternal and child anemia with child brain volumes, accounting for potential confounders.ResultsOf 147 children (mean [SD] age at MRI, 34 [2] months; 83 [56.5%] male) with high-resolution MRI scans, prevalence of maternal anemia in pregnancy was 31.3% (46 of 147; median [IQR] gestation of measurement: 13 [9-20] weeks). Maternal anemia during pregnancy was significantly associated with smaller volumes of the child caudate bilaterally (adjusted percentage difference, −5.30% [95% CI, −7.01 to −3.59]), putamen (left hemisphere: −4.33% [95% CI, −5.74 to −2.92]), and corpus callosum (−7.75% [95% CI, −11.24 to −4.26]). Furthermore, antenatal maternal hemoglobin levels were also associated with brain volumes in the caudate (left hemisphere: standardized β = 0.15 [95% CI, 0.02 to 0.28]; right hemisphere: β = 0.15 [95% CI, 0.02 to 0.27]), putamen left hemisphere (β = 0.21 [95% CI, 0.07 to 0.35]), and corpus callosum (β = 0.24 [95% CI, 0.09 to 0.39]). Prevalence of child anemia was 52.5% (42 of 80; median [IQR] age of measurement: 8.0 [2.7 to 14.8] months). Child anemia was not associated with brain volumes, nor did it mediate the association of maternal anemia during pregnancy with brain volumes.Conclusions and RelevanceIn this cohort study, anemia in pregnancy was associated with altered child brain structural development. Given the high prevalence of antenatal maternal anemia worldwide, these findings suggest that optimizing interventions during pregnancy may improve child brain outcomes.

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Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management

Cited by 322 publications

References 111 publications

Utility of new red cell parameters for distinguishing functional iron deficiency from absolute iron deficiency in children with familial Mediterranean fever

Utility of new red cell parameters for distinguishing functional iron deficiency from absolute iron deficiency in children with familial Mediterranean fever

Iron Deficiency Anemia in Chronic Kidney Disease

Association of Maternal and Child Anemia With Brain Structure in Early Life in South Africa

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