Normal Iron Parameters Research Articles

Clinical Application of Reticulocyte Maturity Indices in Early Diagnosis of Iron Deficiency Anemia in the First Trimester of Pregnancy

Background: Iron deficiency anemia (IDA) is a prevalent global health issue, particularly affecting pregnant females due to increased iron demands during pregnancy. In Pakistan, IDA remains a significant concern, posing challenges to maternal and child health. Early detection and management of iron deficiency are crucial for improving pregnancy outcomes.
 Objective: This study aims to investigate the iron status and associated hematological parameters among pregnant females during the first trimester in Islamabad, Pakistan.
 Methodology : This cross-sectional study, conducted in collaboration with the Pakistan Atomic Energy Commission (PAEC) and the Pakistan Institute of Medical Sciences (PIMS), aimed to investigate the iron status among first-trimester pregnant females in Islamabad, Pakistan.Laboratory investigations encompassed hemoglobin and serum ferritin assays, reticulocyte counts, and other red blood cell parameters. Participants were categorized into distinct iron status groups based on these evaluations. Utilizing SPSS version 25, statistical analysis followed ethical protocols, striving to uncover discrepancies in hematological parameters across the various iron status groups.
 Results : Among 340 first-trimester pregnant women, three iron status groups were identified. Group 1 (n = 102) had low ferritin despite normal Hb, with elevated immature reticulocytes. Group 2 (n = 150) showed normal iron parameters, while Group 3 (n = 88) had high reticulocyte counts. Group 2 exhibited superior erythrocyte indices and higher ferritin levels than Groups 1 and 3. Group 3 displayed the poorest indices and elevated immature reticulocytes. These findings highlight variations in iron status and reticulocyte maturation among pregnant women.
 Conclusion: This study underscores the high prevalence of iron deficiency anemia among first-trimester pregnant females in Islamabad, Pakistan. Variations in red blood cell parameters and serum ferritin levels highlight the importance of early iron status assessment for optimizing maternal and foetal health outcomes.

Ferritin Increase in Hemochromatosis Subjects After Discontinuing Their Regular Maintenance Treatment: A Longitudinal Analysis Performed During the COVID-19 Imposed Hospital Lockdown.

Ferritin Increase in Hemochromatosis Subjects After Discontinuing Their Regular Maintenance Treatment: A Longitudinal Analysis Performed During the COVID-19 Imposed Hospital Lockdown.

The second transferrin receptor regulates red blood cell production in mice

AbstractTransferrin receptor 2 (TFR2) contributes to hepcidin regulation in the liver and associates with erythropoietin receptor in erythroid cells. Nevertheless, TFR2 mutations cause iron overload (hemochromatosis type 3) without overt erythroid abnormalities. To clarify TFR2 erythroid function, we generated a mouse lacking Tfr2 exclusively in the bone marrow (Tfr2BMKO). Tfr2BMKO mice have normal iron parameters, reduced hepcidin levels, higher hemoglobin and red blood cell counts, and lower mean corpuscular volume than normal control mice, a phenotype that becomes more evident in iron deficiency. In Tfr2BMKO mice, the proportion of nucleated erythroid cells in the bone marrow is higher and the apoptosis lower than in controls, irrespective of comparable erythropoietin levels. Induction of moderate iron deficiency increases erythroblasts number, reduces apoptosis, and enhances erythropoietin (Epo) levels in controls, but not in Tfr2BMKO mice. Epo-target genes such as Bcl-xL and Epor are highly expressed in the spleen and in isolated erythroblasts from Tfr2BMKO mice. Low hepcidin expression in Tfr2BMKO is accounted for by erythroid expansion and production of the erythroid regulator erythroferrone. We suggest that Tfr2 is a component of a novel iron-sensing mechanism that adjusts erythrocyte production according to iron availability, likely by modulating the erythroblast Epo sensitivity.

New perspectives of iron deficiency as a risk factor for ischemic stroke

Dear Editor, Stroke is the third leading cause of premature death in general population [1]. In childhood, the occurrence of stroke is less frequent than in adulthood; however, the mortality rate reaches 20 % in infants [2]. For instance, sickle cell disease, congenital cardiac disorders, traumatic lesions, and infections contribute to increase the odds for childhood stroke [3]. Recently, iron-deficiency anemia (IDA) has been also suggested as an important risk factor to ischemic cerebrovascular events [4, 5]. In this context, Azab et al. [6] performed a case–control study with 21 stroke children with median age of 36 months. They found a significant effect of IDA predicting stroke. The patients with IDA showed higher median platelet count compared to control and stroke with normal iron parameters groups. Consequently, children with IDA had 2.5-fold greater odds for ischemic stroke. These results suggest that IDA could be a more potent risk factor for perinatal stroke with similar magnitude than the others widely reported. The authors deserve congratulations for this study mainly for two reasons. Firstly, effective stroke treatments must be continuously investigated since the prevention of reversible risk factors is the most indicated therapy to avoid the occurrence and recurrence of stroke. Secondly, these findings may contribute to elucidate the different pathophysiological mechanism involved in the association of stroke and other disorders, such as the periodic limb movements (PLM) [7], for example. PLM is characterized by repeated movements of arms and/ or legs during sleep whose possible etiology comprises an iron deficiency and a consequent dysfunction in dopaminergic transmission [8]. Indeed, children with sickle cell disease showed a higher PLM prevalence than healthy patients [9]. PLM also increase the risk of ischemic stroke. The high prevalence of PLM after stroke may indicate a concomitant pathway of iron deficiency [7]. Indeterminate etiology of stroke can constitute approximately 37 % of all diagnosed patients [10]. Thus, further studies should be performed to analyze underestimated risk factors for stroke. New and common pathophysiological mechanisms of different diseases with stroke must be better understood. The investigations may contribute to elucidate part of the indeterminate stroke.

Iron deficiency anemia as a risk factor for cerebrovascular events in early childhood: a case–control study

In recent years, iron-deficiency anemia (IDA) has been suggested to have an association with childhood-onset ischemic stroke in otherwise healthy children, but few cases have proven it thus far. In this study, we aimed to investigate whether iron-deficiency anemia is a risk factor for cerebrovascular events and childhood-onset ischemic stroke in previously healthy children. This was a case-control study that included 21 stroke cases with patients who had previously been generally healthy, and matched with age and gender of 100 healthy control subjects. Patients were included if a diagnosis of definite stroke had been made and other known etiologies of childhood onset stroke were excluded. For all subjects, iron parameters including serum iron, ferritin, transferrin, total iron binding capacity, and transferrin saturation were assessed. We screened all case patients for prothrombotic factors including level of hemoglobin S, protein C, protein S, antithrombin III, lupus anticoagulant, factor V Leiden, and prothrombin gene mutation (G20210A). Brain magnetic resonance images (MRI), magnetic resonance angiography (MRA), and magnetic resonance venography (MRV) were performed to all case patients. All case patients have normal results regarding functional, immunological, and molecular assay for prothrombotic factors screening. Our results showed that IDA was disclosed in 57.1 % of stroke cases with no identified cause, as compared to 26 % of controls. Our study suggest that previously healthy children who developed stroke are 3.8 times more likely to have IDA than healthy children, who do not develop stroke (OR, 3.8; 95 % CI:1.3-11.2 P = 0.005). In addition, there was significant interaction between IDA and thrombocytosis among studied cases (OR, 10.5; 95 % CI, 1.0-152 P = 0.02). There were nonsignificant differences between stroke patients with IDA and those with normal iron parameters regarding stroke subtype (P > 0.05). Public health messages on the importance of early detection of iron-deficiency anemia in young children, especially in our developing countries so that it can be treated before a life-threatening complication like stroke develops.

Variable age of onset and clinical severity in transferrin receptor 2 related haemochromatosis: novel observations

Variable age of onset and clinical severity in transferrin receptor 2 related haemochromatosis: novel observations

Identification and characterization of the first SLC11A2 isoform 1a mutation causing a defect in splicing process and an hypomorphic allele expression of the SLC11A2 gene

Identification and characterization of the first <scp>SLC</scp>11<scp>A</scp>2 isoform 1a mutation causing a defect in splicing process and an hypomorphic allele expression of the <i><scp>SLC</scp>11<scp>A</scp>2</i> gene

Iron studies and red cell transfusion in cardiothoracic and orthopaedic surgical patients: a retrospective audit at a tertiary hospital

Preoperative diagnosis and treatment of anaemia are important to minimize adverse postoperative outcomes. This audit reviewed red cell transfusion practice, degree of anaemia, iron deficiency anaemia (IDA) and chronic disease or anaemia of inflammation (AI) in cardiothoracic and orthopaedic surgical patients who had available iron studies. A total of 178 consecutive cardiothoracic and orthopaedic surgical patients with available iron studies were retrospectively reviewed. Of patients, 36·5% had preoperative iron studies. However, 63·2% males and 45·3% females with postoperative iron studies presented with anaemia; 38·5% patients with preoperative iron studies had AI; 21·5% IDA; 23·1% normal. For patients with iron studies requested within the first two postoperative intervals (≤ 5 days and 6 ≤ 10 days) 73·8% and 63·6%, respectively, had AI; few had classical IDA or were normal, and 51·5% patients transfused postsurgery had a discharge Hb ≥ 110 g/l. Restricting the discharge Hb to 90 or 100 g/l may have eliminated postsurgical transfusion in 14·8-42·6% patients. Iron studies were more commonly requested postoperatively despite many being anaemic at admission. A higher proportion of patients with postoperative iron studies had AI, and few had classical IDA or normal iron parameters, suggesting a transient inflammatory effect of surgery. This may mask underlying IDA or normal iron parameters and affect treatment. Preadmission assessment, including iron status, should be emphasized allowing diagnosis and correction of presurgical anaemia with treatment modalities other than red cell transfusion. In the postsurgical setting, consideration of a restrictive transfusion regimen sufficient to alleviate a patient's clinical symptoms would ensure that this valuable resource is appropriately used.

Iron Depleted Erythropoiesis: Slow but Effective

Iron deficiency affects billions worldwide, and anemia develops when iron stores become insufficient to maintain normal erythropoiesis. However, iron depleted erythropoiesis is incompletely understood. In this study, an ex vivo model of iron depleted erythropoiesis was developed using dosed titrations of the iron chelator deferoxamine (DFO) in CD34+ cell cultures. All experiments were performed in triplicate with cells from three separate donors. Hemoglobinization and expression patterns of erythroid markers (GPA/CD71) demonstrated minimal changes in DFO supplemented medium. DFO caused dose-related suppression of cell counts after 14 days (20uM DFO: 42% reduction, 30uM DFO: 86% reduction, 40uM DFO: 96% reduction of cell counts compared to 0uM DFO controls). Cultures supplemented with 30uM DFO were used for subsequent studies, and the DFO-mediated effects were completely reversed by addition of 30uM ferric chloride. To investigate whether apoptosis caused the reduction in cell counts, surface Annexin V was measured by flow cytometry. No significant increases in levels of apoptosis among the proliferating erythroblasts were detected (Annexin V positive cells; 0uM DFO 6.2 ± 0.95%, 30uM DFO 9.0 ± 1.55%, p = 0.058). Analyses of p53 protein quantitation and p53 DNA-binding activity further suggested that the suppression of cell counts by iron chelation was not due to p53 related apoptosis. In the absence of apoptosis or maturation arrest, we hypothesized that the growth suppressing effects of DFO were not due to ineffective erythropoiesis. To test this hypothesis, a recently-discovered marker of ineffective erythropoiesis named GDF15 (Tanno et al. Nat. Med. 2007) was measured in the culture supernatants, and no increase was detected (GDF15 concentration per 1×104 cells: 0uM DFO; 79.7 ± 4.4 pg, 30uM; 43.9 ± 4.3 pg). In the clinic, serum GDF15 levels from 17 blood donors with significantly reduced ferritin and iron saturation (279 ± 98 pg/ml) were not increased when compared to serum GDF15 levels in 17 healthy volunteers with normal iron parameters (410 ± 119 pg/ml). To determine if cell cycling, instead of apoptosis, caused the reduction in cell counts, carboxyfluorescein diacetate succinimidyl diester (CFSE) staining studies were performed during the first and second weeks of culture. CFSE is an intracellular fluorescent stain, the intensity of which halves with each cell division. Three or four fewer erythroblast cell divisions were detected in 30uM DFO during the 14-day culture period when compared to controls. Based upon the reduction in cell divisions, it was estimated that the average cell cycle time was prolonged by 40–70% in DFO. Propidium iodide analyses additionally demonstrated changes in the cell cycle kinetics including a significant reduction in the percentage of S-phase erythroblasts at the peak phase of proliferation (30uM DFO: 37.0 ± 1.8% vs. control: 48.7 ± 3.4%, p = 0.0063). These results suggest that iron depletion inhibits the overall growth of erythroblasts by prolonging the cell cycle rather than causing apoptosis or maturation arrest. Due to the large amount of iron required for hemoglobin production, slower cell cycles may facilitate effective erythropoiesis by allowing extra time for uptake when extracellular iron is scarce.

Hepatic iron metabolism gene expression profiles in HFE associated Hereditary Hemochromatosis

Background: Individuals with pathogenic mutations in HFE, hemojuvelin (HJV) and transferrin receptor 2 (TfR2) have low levels of hepcidin, but little is known about the hepatic expression of these molecules in patients with physiological iron overload or HFE associated Hemochromatosis (HH). Aims: To examine the hepatic mRNA expression of iron homeostasis genes in patients with HH, physiological iron overload and healthy controls. Patients: Untreated C282Y homozygous HH patients ( n = 20) with elevated serum ferritin (SF) and patients with physiological iron overload ( n = 12) with positive hepatocellular iron staining and negative HFE mutation analysis were evaluated. The control cohort ( n = 10) had normal iron parameters, negative HFE mutation analysis and negative hepatocellular iron staining. Methods: Hepcidin, HJV (hemojuvelin), TfR2 (transferrin receptor 2), HFE, IL6 (interleukin 6) and ferroportin mRNA expression patterns were evaluated using quantitative real-time PCR. Results: Physiological iron overload led to significantly upregulated hepcidin, HJV and ferroportin mRNA expression while TfR2 expression was not significantly different to controls. In contrast, HFE associated iron overload failed to induce hepcidin or HJV. TfR2 mRNA expression was significantly reduced when compared to controls. Ferroportin expression in HH was comparable to that found in physiological iron overload. Neither HFE nor IL6 expression was altered by variation in iron status. Conclusions: These findings suggest that patients with HH, in contrast to those with physiological iron overload, have a weakened TfR2 sensing mechanism that leads to the lack of induction of hepcidin and HJV. The C282Y HFE mutation does not appear to impede the hepatocellular iron export function of ferroportin.

Abnormal Hematologic Screening in an Elite Athlete

HISTORY: The patient is a 21-year-old male, elite level athlete who competes in a sprinting sport. He has no medical concerns other than some low back pain (common in his sport). Routine laboratory testing had documented elevated hemoglobin and hematocrit levels since he was first tested about 4 years previously. He was in the process of obtaining a Blood Passport from his athletic governing body which grants permission to compete based upon documentation of elevated hematocrit levels from adolescence to present time. His latest screening also demonstrated an elevated total serum iron and iron saturation for the first time. He has a family history of some relatives with elevated blood counts who were thought to be otherwise healthy. PHYSICAL EXAMINATION: Routine yearly physical examinations had previously revealed no abnormalities. Laboratory screening examinations were performed several times a year to monitor blood levels consisting of Complete Blood Count (CBC), Ferritin, Serum Iron, and Total Iron Binding Capacity. The following values were obtained during the above mentioned screening exam (abnormal levels are in bold): RBC - 5.96 (n 4.5–5.9), Hgb - 19.3 (n 13.5–17.5), Hct -55.8 (n 41.0–53.0), Ferritin- 211 (n 20–300), Total Serum Iron - 200 (n 49–181), Total Iron Binding Capacity - 389 (n 250–450), Iron Percent Saturation - 51 (n 20–50). DIFFERENTIAL DIAGNOSIS: Constitutionally high hemoglobin Polycythemia Hemochromatosis Altitude induced hematopoesis Erythropoetin (EPO) usage TEST AND RESULTS: Given a change in the the previously normal iron parameters, coupled with an elevated Hgb and Hct, a fasting serum transferrin saturation was ordered and found to be 45%. Genetic testing for hemochromatosis was obtained via Polymerase Chain Reaction (PCR), which showed: C282Y Hemochromatosis Mutation: Heterozygous H63D Hemochromatosis Mutation: Heterozygous S65C Hemochromatosis Mutation: Negative Final/Working diagnosis: Hereditary Hemochromatosis TREATMENT AND OUTCOMES: The diagnosis of hemochromatosis in an elite athlete in an Olympic year played an important part in this athlete's management process. Further testing, including liver biopsy to determine the extent of end organ iron deposition, was deemed safe to delay until after Olympic competition. No phlebotomizing was started. Most importantly, notification and further evaluation of several of the athlete's family members was initiated, including a grandmother who additional history revealed had both diabetes and a “dark complexion.” This is a rare event when “routine blood screening” has revealed significant abnormalities, with implications for both the athlete and his family.

Reverse cascade screening of newborns for hereditary haemochromatosis: a model for other late onset diseases?

Background: Genetic testing can determine those at risk for hereditary haemochromatosis (HH) caused by HFE mutations before the onset of symptoms. However, there is no optimum screening strategy, mainly owing...

Trypanosoma congolense: erythrocyte indices, plasma iron turnover and effects of treatment in infected cattle

Early during the course of Trypanosoma congolense infection in cattle decreases in PCV occurred and coincided with increases in both MCV and MCH. The indices reached highest levels between eight and 12 weeks post-infection. By week 20 of infection MCV and MCH had decreased to pre-infection levels even though a substantial anemia persisted. Serum iron levels were elevated at eight weeks postinfection. (Infected 271 mg dl-1 v. control 140 mg dl-1) but decreased to low levels in infected animals by Week 28 (63 mg dl-1). At eight weeks post-infection PITR was elevated in infected animals (infected 2.6 mg dl-1 day-1 v. control 0.82 mg dl-1 day-1). By Week 28, however, PITR had fallen in infected animals to 0.62 mg dl-1 day-1 indicating a severe dyshaemopoesis since PCV levels averaged only 22%. Cattle which were treated with Berenil or that self-cured the infection had normal iron parameters when tested 61 weeks post-infection. Cattle treated early during the course of infection showed a significantly greater PCV response that those treated later during infection.