The Diagnostic Value of Serum Ferritin in Assessing Iron Status in Syrian Hemodialysis Patients

Introduction: The gold standard for the diagnosis of absolute iron-deficiency anemia (IDA) in hemodialysis patients is a bone marrow aspirate with iron staining. Many clinicians use peripheral iron indices instead because they are non-invasive. Previous studies suggested that a serum ferritin < 200 ng/mL was a reliable indicator of absolute iron deficiency in the hemodialysis population. However, the sensitivity of serum ferritin for the diagnosis of IDA in hemodialysis patients is poor. Methods: The primary objective of this study was to identify the optimal ferritin value to diagnose patients with absolute iron deficiency, as assessed on bone marrow aspiration, in the renal dialysis population. Secondary endpoints included the rate of clinically relevant findings on gastrointestinal investigation according to iron status. Research Ethics Board approval was obtained from Queen's University for this retrospective chart review. Hematopathology laboratory records were used to determine all individuals who had bone marrow examination at Kingston Health Sciences tertiary referral center between 2008 January 1 and 2018 August 21. This list was cross-referenced with the Nephrology dialysis database to identify the pre-specified study cohort; those who were receiving concurrent hemodialysis or peritoneal dialysis. Iron deficiency was defined as reduced or absent iron stores on bone marrow aspirate with Perl's Prussian blue stain. Anemia was defined as hemoglobin <130 g/L in males and <120 g/L in females. Additional parameters collected included ferritin (normal range 22 - 275 ng/mL male and 4 - 205 ng/mL female), transferrin saturation (TSAT, normal range 20-55%), vitamin B12, folate, albumin, CRP and thyroid function tests. Peripheral iron indices over six months were analyzed; statistical analysis was performed with t-tests and Mann-Whitney U tests. ROC curves were generated to determine the sensitivity and specificity of various threshold values for serum ferritin and TSAT. Results: Between 2008 January 1 and 2018 August 21, 4234 patients underwent bone marrow examination, of whom 28 had received renal dialysis replacement therapy at some point. Fifteen patients concurrently at the time of bone marrow testing receiving hemodialysis form the study population (Table 1). Among these fifteen patients, 6 (40%) were female, median age was 70.5 (range 39 - 80) years and all were anemic (Hb range 73 - 110 g/L). Four of these individuals were absolutely iron-deficient with reduced or absent iron stores by bone marrow evaluation. The mean ferritin and TSAT values for individuals with absolute iron deficiency by bone marrow aspiration was 273.5 ng/mL (n=4; median 224.5 ng/mL; range 158-539 ng/mL) and 22.0% (n=3; median 20%; range 20-26%), respectively. All four commenced erythropoietin stimulating agents; two received oral iron supplementation. Eight patients, including two of those determined to be absolutely iron deficient on bone marrow, had endoscopic investigation. Two were identified to have sources of gastrointestinal bleeding, both with ferritin values in the 100-200 range (106 and 189 ng/mL). With the limited sample size, the sensitivity and specificity of ferritin to identify absolute iron deficiency in this hemodialysis population was 50% and 85%, respectively, at a threshold of 198 ng/mL. Discussion: Ferritin and TSAT are not sensitive markers for absolute iron deficiency in hemodialysis patients. Bone marrow examination is performed in a minority. The small sample size in this study precludes definitive determination of an optimal ferritin cut-off to diagnose iron deficiency in the dialysis population. Uncertainty about actual iron status may result in alternative invasive testing, such as colonoscopy, to investigate the cause of their anemia. Newer tests such as reticulocyte hemoglobin content and percent hypochromic red blood cells are more accurate and may guide diagnosis and management of IDA in hemodialysis patients. However they are not always routinely available. Further studies are needed to compare the utility of these peripheral iron indices to the gold standard bone marrow examination in a larger population, to allow identification of patients with absolute or functional IDA, and minimize invasive and potentially unnecessary investigation. Disclosures Hay: AbbVie: Research Funding; Kite: Research Funding; Janssen: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding; MorphoSys: Research Funding; Roche: Research Funding; Novartis: Research Funding; Gilead: Research Funding; Takeda: Research Funding.

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The evaluation of iron status in hemodialysis patients.

Journal of the American Society of Nephrology ◽

10.1681/asn.v7122654 ◽

1996 ◽

Vol 7 (12) ◽

pp. 2654-2657 ◽

Cited By ~ 2

Author(s):

S Fishbane ◽

E A Kowalski ◽

L J Imbriano ◽

J K Maesaka

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Marginal Utility ◽

Iron Status ◽

Transferrin Saturation ◽

Hemodialysis Patients ◽

Mean Cell Volume ◽

Distribution Width ◽

Baseline Serum ◽

Significant Difference

Effective treatment of anemia in hemodialysis patients requires ongoing monitoring of iron status. The purpose of this study was to determine levels of commonly used iron indices predictive of iron deficiency in this population. Forty-seven patients with baseline serum ferritin levels < 600 ng/mL were treated with intravenous iron dextran (INFeD; Schein Pharmaceutical Inc., Florham Park, NJ), 1000 mg over ten hemodialysis treatments. Patients whose hematocrit value increased by 5% or who had a 10% decrease in their erythropoietin dose by 2 months were classified as having iron deficiency (N = 31; 66%). All other subjects were classified as having adequate iron (N = 16; 34%). There was no statistically significant difference in baseline serum ferritin, transferrin saturation, mean cell volume, mean cell hemoglobin content, or red cell distribution width between the two groups. Receiver operator curves demonstrated that none of the iron indices had a high level of utility (both sensitivity and specificity > 80%). Two tests had marginal utility, serum ferritin at a level of < 150 ng/mL, and transferrin saturation < 21%. It was concluded that because of the tests' marginal utility, they should only be interpreted in the context of the patient's underlying erythropoietin, responsiveness. In patients who are responsive to erythropoietin, a transferrin saturation value < 18% or serum ferritin level < 100 ng/mL should be used to indicate inadequate iron. When erythropoietin resistance is present, transferrin saturation of < 27% or serum ferritin < 300 ng/mL should be used to guide iron management.

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Sensitivity and Specificity of Transferrin Saturation and Serum Ferritin as Markers of Iron Status After Intravenous Iron Dextran in Hemodialysis Patients

Renal Failure ◽

10.3109/08860229709037218 ◽

1997 ◽

Vol 19 (6) ◽

pp. 781-788 ◽

Cited By ~ 7

Author(s):

Chai Luan Low ◽

George R. Bailie ◽

George Eisele

Keyword(s):

Sensitivity And Specificity ◽

Serum Ferritin ◽

Iron Status ◽

Transferrin Saturation ◽

Intravenous Iron ◽

Hemodialysis Patients ◽

Iron Dextran

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The Relationship between Serum Ferritin Levels and 5-Year All-Cause Mortality in Hemodialysis Patients

Blood Purification ◽

10.1159/000515639 ◽

2021 ◽

pp. 1-7

Author(s):

Emre Erdem ◽

Ahmet Karatas ◽

Tevfik Ecder

Keyword(s):

Serum Ferritin ◽

Hemodialysis Patients ◽

Rank Test ◽

Significant Difference ◽

All Cause Mortality ◽

Group 3 ◽

Group 2 ◽

The Relationship ◽

Group 1

Introduction: The effect of high serum ferritin levels on long-term mortality in hemodialysis patients is unknown. The relationship between serum ferritin levels and 5-year all-cause mortality in hemodialysis patients was investigated in this study. Methods: A total of 173 prevalent hemodialysis patients were included in this study. The patients were followed for up to 5 years and divided into 3 groups according to time-averaged serum ferritin levels (group 1: serum ferritin <800 ng/mL, group 2: serum ferritin 800–1,500 ng/mL, and group 3: serum ferritin >1,500 ng/mL). Along with the serum ferritin levels, other clinical and laboratory variables that may affect mortality were also included in the Cox proportional-hazards regression analysis. Results: Eighty-one (47%) patients died during the 5-year follow-up period. The median follow-up time was 38 (17.5–60) months. The 5-year survival rates of groups 1, 2, and 3 were 44, 64, and 27%, respectively. In group 3, the survival was lower than in groups 1 and 2 (log-rank test, p = 0.002). In group 1, the mortality was significantly lower than in group 3 (HR [95% CI]: 0.16 [0.05–0.49]; p = 0.001). In group 2, the mortality was also lower than in group 3 (HR [95% CI]: 0.32 [0.12–0.88]; p = 0.026). No significant difference in mortality between groups 1 and 2 was found (HR [95% CI]: 0.49 [0.23–1.04]; p = 0.063). Conclusion: Time-averaged serum ferritin levels >1,500 ng/mL in hemodialysis patients are associated with an increased 5-year all-cause mortality risk.

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Diagnostic Value of Serum Ferritin in Primary Hepatocellular Carcinoma

Digestion ◽

10.1159/000199114 ◽

1984 ◽

Vol 30 (4) ◽

pp. 236-241 ◽

Cited By ~ 8

Author(s):

E. Giannoulis ◽

C. Arvanitakis ◽

A. Nikopoulos ◽

I. Doutsos ◽

A. Tourkantonis

Keyword(s):

Hepatocellular Carcinoma ◽

Serum Ferritin ◽

Diagnostic Value ◽

Primary Hepatocellular Carcinoma

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Diagnostic work up of anemic patients: role of iron deficiency

LaboratoriumsMedizin ◽

10.1515/labmed-2020-0060 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Daniela Meiser ◽

Lale Kayikci ◽

Matthias Orth

Keyword(s):

Iron Deficiency ◽

Complete Blood Count ◽

Iron Status ◽

Area Under The Curve ◽

Diagnostic Value ◽

Diagnostic Tools ◽

Operating Characteristics ◽

Inflammatory Conditions ◽

Reliable Parameter ◽

Work Up

AbstractObjectivesDiagnosing disturbances in iron metabolism can be challenging when accompanied by inflammation. New diagnostic tools such as the “Thomas-plot” (TP) (relation of soluble transferrin receptor [sTfR]/log ferritin to reticulocyte hemoglobin content [RET-He]) were established to improve classification of anemias. Aim of this retrospective study was to assess the added diagnostic value of the TP in anemia work up.MethodsPatients from December 2016 to September 2018 with a complete blood count, iron status, RET-He and sTfR were manually classified into the four quadrants of the TP on basis of conventional iron markers. Manual and algorithm-based classifications were compared using cross tabulations, Box–Whisker-Plots as well as Receiver-Operating-Characteristics (ROC) to calculate the diagnostic accuracy using Area under the Curve (AUC) analysis.ResultsA total of 3,745 patients with a conventional iron status, including 1,721 TPs, could be evaluated. In 70% of the cases the manual classification was identical to the TP, in 10% it was deviant. 20% could not clearly be classified, mostly due to inflammatory conditions. In the absence of an inflammatory condition, ferritin was a reliable parameter to define iron deficiency (ID) (AUC 0.958). In the presence of inflammation, the significance of the ferritin index (AUC 0.917) and of the RET-He (AUC 0.957) increased.ConclusionsThe TP can be useful for narrowing down the causes of anemia in complex cases. Further studies with focus on special patient groups, e.g., oncological or rheumatic patients, are desirable.

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Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome

Microbiome ◽

10.1186/s40168-021-01052-7 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Jordi Mayneris-Perxachs ◽

Marina Cardellini ◽

Lesley Hoyles ◽

Jèssica Latorre ◽

Francesca Davato ◽

...

Keyword(s):

Serum Ferritin ◽

Iron Metabolism ◽

Gut Microbiome ◽

Fatty Liver Disease ◽

Iron Status ◽

Liver Fat ◽

Alcoholic Fatty Liver ◽

Fat Accumulation ◽

Glycine Transporters ◽

Alcoholic Fatty Liver Disease

Abstract Background The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear. Results Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery n = 49 and validation n = 628) and an independent cohort formed by both individuals with and without obesity (n = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality. Specifically, ferritin had strong negative associations with the Pasteurellaceae, Leuconostocaceae and Micrococcaea families. It also had consistent negative associations with several Veillonella, Bifidobacterium and Lactobacillus species, but positive associations with Bacteroides and Prevotella spp. Notably, the ferritin-associated bacterial families had a strong correlation with iron-related liver genes. In addition, several bacterial functions related to iron metabolism (transport, chelation, heme and siderophore biosynthesis) and NAFLD (fatty acid and glutathione biosynthesis) were also associated with the host serum ferritin levels. This iron-related microbiome signature was linked to a transcriptomic and metabolomic signature associated to the degree of liver fat accumulation through hepatic glucose metabolism. In particular, we found a consistent association among serum ferritin, Pasteurellaceae and Micrococcacea families, bacterial functions involved in histidine transport, the host circulating histidine levels and the liver expression of GYS2 and SEC24B. Serum ferritin was also related to bacterial glycine transporters, the host glycine serum levels and the liver expression of glycine transporters. The transcriptomic findings were replicated in human primary hepatocytes, where iron supplementation also led to triglycerides accumulation and induced the expression of lipid and iron metabolism genes in synergy with palmitic acid. We further explored the direct impact of the microbiome on iron metabolism and liver fact accumulation through transplantation of faecal microbiota into recipient’s mice. In line with the results in humans, transplantation from ‘high ferritin donors’ resulted in alterations in several genes related to iron metabolism and fatty acid accumulation in recipient’s mice. Conclusions Altogether, a significant interplay among the gut microbiome, iron status and liver fat accumulation is revealed, with potential significance for target therapies.

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Iron and Hematological Status among Adolescent Athletes Tracked through Puberty

Pediatric Exercise Science ◽

10.1123/pes.7.3.253 ◽

1995 ◽

Vol 7 (3) ◽

pp. 253-262

Author(s):

Noreen D. Willows ◽

Susan K. Grimston ◽

David J. Smith ◽

David A. Hanley

Keyword(s):

Adverse Effect ◽

Iron Deficiency ◽

Serum Ferritin ◽

Direct Evidence ◽

Iron Status ◽

Normal Range ◽

Pubertal Stage ◽

Physically Active ◽

Pubertal Stages ◽

Prepubertal Boys

This study assessed change in hematological status among physically active children as they progressed through puberty. Values for serum ferritin, hemoglobin, and hematocrit at all stages of puberty were within the normal range of reference values. Significant changes in serum ferritin were not detected in the different pubertal stages, although serum ferritin was highest in prepubertal boys and girls. There were no significant differences in marginal or deficient iron stores between the sexes at any pubertal stage, suggesting that gender was not predisposing for iron deficiency; however, girls had a greater overall incidence for both measures. With more children under consideration, these trends may have reached significance. Boys in TS4 and TS5 had higher hemoglobin and hematocrit compared with earlier stages of puberty, and compared with girls at the same stages of puberty. This can be explained by testosterone production in boys. Among girls, pubertal progression had no significant effect on hemoglobin or hematocrit. In the absence of controls, there was no direct evidence that involvement in sports had an adverse effect on iron status.

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