Reticulocyte Hemoglobin Research Articles

Can New Advanced Clinical Parameters Be Used in the Diagnosis of Vitamin B12 Deficiency?

The measurement of vitamin B12 levels has low sensitivity for the diagnosis of vitamin B12 deficiency, therefore, clinicians may prefer to decide the deficiency with the patient's clinic. In this study, the diagnostic values of the classical and advanced clinical complete blood count parameters were investigated to find a new marker in the diagnosis of vitamin B12 deficiency. 150 adult volunteers were included in the study and volunteers were divided into two groups according to their vitamin B12 levels (with or without vitamin B12 deficiency) and hemoglobin levels (with or without anemia). The differences and correlations of laboratory test results between groups were examined. Equivalent of reticulocyte hemoglobin, equivalent of erythrocyte hemoglobin and delta-hemoglobin were found significant differences between groups with or without vitamin B12 deficiency. Hypo-hemoglobinised red cells and hyper-hemoglobinised red cells were found significant difference between groups with or without anemia. Significant positive correlations were found between vitamin B12 levels and equivalent of reticulocyte hemoglobin, equivalent of erythrocyte hemoglobin and delta-hemoglobin. Significant positive correlations were found between hemoglobin levels and macrocytic red blood cells, equivalent of reticulocyte hemoglobin, equivalent of erythrocyte hemoglobin, delta hemoglobin and hyper-hemoglobinised red cells; negative correlations with microcytic red blood cells and hypo-hemoglobinised red cells. It is suggested that these advanced clinical parameters of complete blood count analysis may be used to determine vitamin B12 deficiency.

Biological variation and analytical performance specification study of erythrocyte and related parameters

Objective: To study biological variation (BV) and analytical performance specifications (APS) of 15 erythrocyte and related parameters. Methods: Sixty healthy participants from Beijing Hospital were prospectively recruited for the study, from July to December, 2023, including 30 males [aged (41.3±11.9) years] and 30 females [aged (40.3±12.4) years]. The study was designed based on the Biological Variation Data Critical Appraisal Checklist and the characteristics of erythrocyte detection. Whole blood samples were collected 10 times at 2-week intervals during 20 weeks. All samples were tested in duplicate using Mindray BC-7500 hematology analyzer and its accompanying reagents. Within-subject biological variation (CVI) and between-subject biological variation (CVG) were estimated by the nested ANOVA method. The BV data in this study were compared with the BV data of the European Database of Biological Variation. APS, reference change value (RCV) and index of individuality (II) were calculated. Results: The CVI for 15 parameters ranged from 0.49% to 86.46%, and the CVI data for red cell distribution width (RDW)-CV, RDW-SD, reticulocyte (RET) percentage, RET count, reticulocyte hemoglobin content (RHE), medium fluorescence reticulocyte (MFR) and high fluorescence reticulocyte (HFR) were significantly higher in females than in males (all P<0.05). The CVG ranged from 1.27% to 100.79%, and the CVG data for HFR were significantly different between genders (P<0.05). The CVI data for red blood cell (RBC), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and RHE in this study were lower than those recommended by the European database. The derived indicators of most parameters were influenced by gender. The II values for all parameters were<1.4, where the II values of MCHC and HFR were between 0.6 and 1.4; the II values for the remaining 13 parameters were<0.6. Conclusions: A BV study protocol for erythrocyte parameters is designed. When the reference intervals differ between genders, BV data should be calculated separately and the lower BV data are recommended for calculating APS; the RCV should be set separately for each gender.

Iron status in children with acute COVID-19 and paediatric inflammatory multisystem syndrome during infection and after recovery

BackgroundCOVID-19 has significant effects on organ function, particularly on lung function and iron metabolism. Studies have shown increased levels of ferritin, an iron storage protein, in COVID-19 patients, indicating potential changes in iron utilization. Research has focused primarily on adults, with limited studies on paediatric patients and a lack of comparisons with MIS-C patients. This study aimed to assess iron status in paediatric COVID-19 patients using traditional and new biomarkers, soluble transferrin receptors (sTfR) and Reticulocyte hemoglobin equivalent (RET-He), to improve diagnosis and prognosis. Additionally, we sought to compare iron status between acute COVID-19 patients and MIS-C patients and evaluate the relationships among iron dysmetabolism, disease severity, and prognosis in paediatric patients. The study also involved monitoring iron status during and after infection to understand its impact on patient severity and prognosis.MethodsA cohort study involving 49 patients aged 1 month to 18 years was conducted at the isolation department of Mansoura University Children's Hospital. The study included 36 patients with acute COVID-19 and 13 with multisystem inflammatory syndrome of childhood (MIS-C). Diagnosis was based on PCR from a deep nasopharyngeal swab or a positive antibody test. Follow-up of survivors was conducted 3 months after recovery. Blood samples were obtained during infection and at follow-up for CBC, Ret-He, iron kinetics, and sTfR analyses.ResultsSignificant iron deficiency anaemia was observed in all patients during infection, with improvement after 3 months of recovery in survivors. The improvement was more obvious in MIS-C patients, with Hb and iron kinetics not significantly affected by disease severity. The STfR was significantly lower in nonsurvivors than in survivors. The ROC curve showed that a baseline sTfR ≤ 18 nmol/L was a statistically significant difference between nonsurvivors and survivors (area under the curve (AUC) = 0.810, p < .001), with 66.7% sensitivity and 82.5% specificity. Regression analysis revealed that patients with baseline sTfRs ≤ 18 nmol/L were 5.9 times more susceptible to death.ConclusionThis study revealed that COVID-19 in children caused iron deficiency anaemia, which improved within 3 months after recovery. Haemoglobin and sTfRs were identified as reliable indicators of IDA in these patients, unlike iron kinetics and RET-He.

Assessment of myeloid response and iron status among Sudanese pediatric ESKD on hemodialysis through reticulocyte parameters and β-globin mRNA expression

BackgroundSudanese children with End-Stage Kidney Disease (ESKD) often show limited improvement in hemoglobin levels despite treatment with recombinant human erythropoietin (rHuEPO). This study aims to assess the response to rHuEPO therapy by analyzing β-globin mRNA expression and reticulocyte parameters. Additionally, it classifies anemia among Sudanese pediatric patients based on iron status, considering age and gender as biological markers for evaluating treatment response.MethodsA prospective observational cohort study was conducted from January 2019 to February 2020 in Khartoum, Sudan, involving 45 anemic children aged 2 to 15 years diagnosed with ESKD. The treatment protocol included rHuEPO injections and maintenance hemodialysis. Laboratory assessments consisted of complete blood count (CBC), absolute reticulocyte count, ferritin, and transferrin measurements. β-globin mRNA expression was quantified using reverse transcription polymerase chain reaction (RT-PCR), and reticulocyte parameters, including Reticulocyte Hemoglobin Content (CHr), percentage of hypochromic reticulocytes (HYPO%), and Immature Reticulocyte Fraction (IRF), were measured via flow cytometry.ResultsSignificant variations in hemoglobin levels were observed across different age groups (p = 0.011). Gender analysis revealed a significant association with IRF, showing a lower IRF in male patients (p = 0.017). However, there were no significant differences in hemoglobin levels between genders (p = 0.999). β-globin mRNA expression showed considerable variability, with a strong positive correlation with hemoglobin levels (r = 0.875, p < 0.0001).ConclusionAge and gender significantly influence treatment responses in children with ESKD, highlighting the need to consider growth physiology in anemia management. This study underscores the variability in β-globin mRNA expression and its association with Flow Cytometry parameters, demonstrating their effectiveness in evaluating iron status and guiding rHuEPO dosage.

56 Iron deficiency is common in extreme preterm infants despite prophylactic iron supplementation

Abstract Background Iron deficiency (ID) in childhood is linked to adverse neurodevelopmental outcomes in the long-term. Extremely premature infants (EPI; born &amp;lt; 28 weeks gestation) are more susceptible to ID due to a multitude of factors including lower iron reserves at birth, rapid growth, immature erythropoiesis, and multiple phlebotomy tests during hospital stay. Therefore, professional societies advise prophylactic iron therapy for these infants from 2-6 weeks age until 6-12 months. However, there is paucity of data on the iron status in EPI receiving this prophylactic iron supplementation. Objectives To investigate the prevalence and risk factors associated with ID in EPI. Design/Methods A retrospective cohort study analyzed a Provincial database of EPIs born between 2005-2018. Infants with congenital malformations, chromosomal anomalies and blood disorders were excluded. All included infants received prophylactic iron supplementation from 2-4 weeks of chronological age that was recommended to continue at discharge until 9-12 months corrected age (CA). At 4-6 months CA, these infants underwent blood testing. ID was defined as serum ferritin &amp;lt; 20mcg/L at 4 months CA or SF &amp;lt; 12mcg/L at 6 months CA. Through a univariate analysis using single-variable logistic regression, factors linked to ID were identified. Those with a p-value &amp;lt; 0.20 progressed to a multivariable model, retaining variables with a p-value &amp;lt; 0.05. Results Of 146 infants, 45.9% had ID. ID group had lower mean ferritin (16.4 µg/L vs 50.0 µg/L, p &amp;lt; .001) and reticulocyte hemoglobin equivalent (28.4pg vs 31.6pg, p &amp;lt; .001) compared to the non-ID group. ID prevalence reduced from 59.7% in 2005-2011 to 40.3% in 2012-2018 cohort. Exclusive or partial breastfeeding at 4-6 months CA was protective against ID (Odds: 0.2, p = 0.003). Iron therapy at 4-6 months CA was not protective in the final model. Notably, 27.4% stopped iron therapy before 4-6 months CA, and exclusive formula-fed infants had notably lower iron intake than breastfed infants (66.1% vs 99.1%, p = 0.006). Conclusion Nearly half of the EPI exhibited ID at 4-6 months CA despite prophylactic iron supplementation. About a quarter discontinued therapy before reaching this age. Breastfeeding at this age was protective against ID. This high prevalence of ID in EPI underscores the need of future studies to discern strategies to mitigate ID in this vulnerable population.

Utility of Reticulocyte Hemoglobin Equivalent in Screening for Iron Deficiency in Pregnancy.

Ferritin, commonly used for diagnosing iron deficiency (ID) in pregnancy, is limited by high cost and false elevations during inflammation. Reticulocyte hemoglobin equivalent (Ret-He), an alternative marker for ID, is unaffected by inflammation and analyzed on the same collection tube as the standard complete blood count (CBC). We aimed to determine the accuracy of Ret-He in detecting ID in pregnancy compared to ferritin in a U.S. This prospective cohort study enrolled 200 pregnant participants, recruited in any trimester if a CBC was drawn as part of routine prenatal care. For those who agreed to participate, Ret-He and ferritin were collected concurrently with the CBC. ID was defined as ferritin level below 30 ng/mL. Patients were classified into three groups based on hemoglobin and ferritin results to determine the severity of ID: no ID, ID alone, and ID anemia (IDA). Four participants with anemia but normal ferritin were excluded. Receiver operating curve analysis, including the area under the curve (AUC), was performed to assess the accuracy of Ret-He in detecting ID. A one-way ANOVA (analysis of variance) with post-hoc analysis was used to compare differences in Ret-He between the three groups of ID severity. The prevalence of ID in our cohort was 82% (161/196). The AUC for Ret-He was 0.65 (95% confidence interval: 0.55-0.75), indicating suboptimal discrimination between patients with and without ID. Ret-He was significantly different among the three groups (p < 0.001). In post-hoc analysis, Ret-He was significantly lower in the IDA group compared to the ID group (p < 0.001) but there was only a trend of lower Ret-He in the ID group compared to the non-ID group (p = 0.38). Ret-He has low accuracy in diagnosing ID in pregnancy. It may be useful in detecting severe ID resulting in anemia but not a mild iron-deficient state resulting in ID only. · The prevalence of ID in our cohort was 82%.. · Ret-He has low accuracy in diagnosing ID in pregnancy.. · Ferritin is preferable when readily available..

Dynamics and prognostic repeatability of qualitative and quantitative blood characteristics in patients with new coronavirus infection

The study presents the possibility of using clinical blood test indicators characterizing the red hematopoietic germ in diagnosing the severity of the clinical condition of patients with COVID-19.Aim: Dynamic monitoring of changes in the quantitative and qualitative characteristics of erythrocytes and reticulocytes to identify parameters that characterize the severe course of a new coronavirus infection in patients with cardiovascular pathology.Material and Methods. The study included 94 patients with a confirmed diagnosis of a novel coronavirus infection (NCI), hospitalized in the department for the treatment of patients with CVD and COVID-19 with intensive care unit on the basis of the Academician L.S. Barbarasha between February and March 2022. Clinical blood analysis was performed on the 1st, 3rd and 7th day of hospitalization. Whole blood with K2EDTA was studied on a Sysmex XN-1000 hematological analyzer.Results. To determine the diagnostically significant indicators of a clinical blood test, patients were divided into 2 comparison groups: group 1 – 71 people with a mild infection, group 2 – 23 people with moderate, severe and extremely severe NCI. On the first day of observation, 70% of patients in the group of unfavorable course were diagnosed with anemia, while in the group of mild course, 38% of patients were diagnosed. In patients with unfavorable development of the disease, normoblastemia was observed, which, according to the results of regression analysis, increased the risk of an unfavorable course by 5 times OR 0.24 (95% CI 0.07–0.884). Also in the severe group, there was a decrease in hemoglobin saturation of reticulocytes, which was expressed in deficient Ret-He and negative Delta-Hb values. Using binary logistic regression, it was found that a negative Delta-Hb 6 times increases the risk of an unfavorable course of NCI, OR 6.18 (95% CI 1.971–19.3).Conclusion. The parameters of a clinical blood test that characterize the hemoglobinization of reticulocytes reflect the severity of the course of a new coronavirus infection and can be used to assess the clinical condition of patients with this infection.

The Diagnostic Value of Ret-He in Predicting Latent Iron Deficiency in Female Blood Donors

To explore the application value of reticulocyte hemoglobin equivalent (Ret-He) for diagnosing latent iron deficiency in female plateletpheresis donors. A total of 230 female plateletpheresis donors in Fujian Blood Center from January to February 2022 were selected as the research group and divided into three groups: normal group, iron depletion (ID) group and iron deficient erythropoiesis (IDE) group, according to the severity of iron deficiency. The level of hemoglobin (HGB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), coefficient of variation of red cell distribution width (RDW-CV) and Ret-He were measured by using the Sysmex XN automated hematology analyzer. Chemiluminescence immunoassay was used to detect iron biochemical indexes. Receiver operating characteristic(ROC) curve analysis was performed to evaluate the diagnosic value of relevant indicators in female blood donors with latent iron deficiency. Ret-He in ID group was 32.55 (31.15,33.10)pg, which was significantly lower than that in the normal group ［33.80(32.73，34.70)pg］ （P <0.05）, and significantly higher than that in IDE group ［30.40(28.70,31.50)pg］ （P <0.05）. ROC analysis in diagnosis of IDE demonstrated that the area under the curves (AUCs) of HGB, MCV, MCH, RDW-CV and Ret-He were 0.892, 0.843, 0.909, 0.890, 0.931, respectively. When the critical value of Ret-He was 32.05 pg, its sensitivity and specificity were 85.90% and 92.60%, respectively. However, all red blood cell parameters had poor diagnostic value for ID. Ret-He is a perfect predictor for latent iron deficiency in female blood donors. Detection of Ret-He can advance the diagnosis of iron deficiency in female blood donors to the IDE stage.

Red cell size factor is a sensitive index in the early diagnosis of nondigestive tract cancer-related anemia: An observational study.

Cancer-related anemia (CRA) is a common comorbidity in cancer patients, and it can lead to a worse prognosis. The aim of this cross-sectional study is to investigate the clinical value of the red cell size factor (Rsf) in the early diagnosis of nondigestive tract CRA. A total of 231 patients with nondigestive tract solid cancer were included, and they were divided into anemic and nonanemic subjects according to the hemoglobin (Hb) levels. A BC-7500 blood analyzer was used to detect the indices of red blood cell and reticulocyte, and the mean corpuscular volume (MCV), mean reticulocyte volume (MRV), reticulocyte hemoglobin (RHE) content, and reticulocyte production index were observed. Subsequently, the Rsf was calculated. Receiver operating characteristic curve analysis was used to evaluate the identifying power of Rsf for anemia diagnosed by the combination of RHE and reticulocyte production index. The adjusted-multivariate analysis and quartiles were used to assess the relation of reduced Rsf level with the risk and incidence of anemia diagnosed by combining the MCV, MCH, and mean corpuscular hemoglobin concentration (MCHC), respectively. Rsf levels showed no statistical differences between anemia and nonanemia subjects grouped by Hb (P > .05). Rsf has a high correlation with the RHE level (R > 0.900, P < .001), or MCV, mean corpuscular hemoglobin (MCH), and MCHC in anemia patients (r: 0.435-0.802, P < .001). Receiver operating characteristic curves showed that Rsf had the highest overall area under curve of 0.886 (95% confidence interval: 0.845-0.927) in identifying anemia of cancer patients (P < .001). When the optimal cutoff values of Rsf were set at 97.05 fl in males and 94.95 fl in females, the sensitivity and specificity were 0.94 and 0.76, and 0.98 and 0.75, respectively. Being treated as a categorical variable, Rsf had a highest odds ratio value of 30.626 (12.552-74.726; P < .001) for the risk of anemia. The increment of Rsf quartiles was highly associated with the decreased incidence of overall anemia (P trend < 0.001). The study suggests that decreased Rsf level is a potentially powerful predictor of overt anemia in nondigestive tract cancer, and it can be used as a convenient, practical, cost-free, and sensitive index in early diagnosis of nondigestive tract CRA.

Reticulocyte haemoglobin content in the differential diagnosis of iron deficiency anaemia and thalassemia traits in pregnancy

Background: Iron deficiency anaemia (IDA) and thalassemia traits are the common conditions of microcytic hypochromic anaemia in pregnant women. However, the laboratory tests to differentiate them are expensive. The reticulocyte haemoglobin (Ret-Hb) test is relatively cheap. This study aimed to assess whether Ret-Hb can differentiate IDA from thalassemia traits in pregnant patients. Method: This cross-sectional study was conducted in the Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2023 to February 2024. We recruited pregnant women aged 18 to 40 through antenatal visits in the Obstetrics and Gynecology Department. Microcytic hypochromic anaemia was diagnosed by complete blood counts, IDA by iron profile and thalassemia traits by haemoglobin electrophoresis. Ret-Hb was measured using the flow cytometric method. Ninety pregnant women—30 each with IDA, thalassemia traits and healthy individuals—were enrolled. Result: The mean age was 27 years. The IDA patients had significantly (P&lt;0.001) lower levels of Ret-Hb (mean 18.1, standard deviation 3.2 pg) compared to thalassemia traits (20.8, 2.2 pg) and healthy pregnant women (29.2, 1.9 pg). Using a Ret-Hb cut-off point of 19 pg, the test had 86.7% sensitivity and 53.3% specificity to differentiate thalassemia traits from IDA. Conclusion: Ret-Hb could be considered a diagnostic test to differentiate thalassemia traits from IDA in clinical settings before expensive confirmatory tests are performed.

From the marrow to the blood: Optimising the diagnosis of iron deficiency in the setting of inflammation

Iron deficiency (ID) is a common condition with readily available treatment but can be challenging to diagnose. Traditional biomarkers of ID are acute-phase reactants, which complicate diagnosis in patients with co-existent inflammation. This study aimed to establish optimal biomarker diagnostic thresholds for ID diagnosis using bone marrow (BM) iron stores as the gold standard and the C-reactive protein (CRP) as an inflammatory marker. A cross-sectional study was carried out in the haematology department of a tertiary academic hospital. Patients undergoing BM biopsies for any reason were recruited for inclusion. Retrospective case finding was used to enrich the data for cases with confirmed BM ID. Laboratory markers including red cell indices, reticulocyte haemoglobin and iron studies were evaluated to establish optimal cut-offs for ID diagnosis. A CRP of >5 mg/L was used as a marker of inflammation. The study included 139 patients. Forty-two had BM ID, with a median serum ferritin (SF) of 48.5 μg/L. Ninety-six of 134 (72%) had inflammation with a CRP >5mg/L. An SF of <80 μg/L had optimal sensitivity (69%) and specificity (94%) for ID diagnosis in the whole group (odds ratio: 23.5; confidence interval: 4.3–129). In patients without inflammation, an SF cut-off of 80-μg/L had high sensitivity (93%) and specificity (96%). An SF <200 μg/L indicated ID in those with inflammation (sensitivity: 78%, specificity: 74%). A transferrin saturation of <13% in those with inflammation increased the diagnostic specificity (92%). The reticulocyte haemoglobin was unhelpful in diagnosing ID in this setting. In this hospital population, SF was the best parameter to diagnose ID, even in the presence of inflammation. The CRP was useful to identify populations with inflammation in whom higher SF thresholds could be used together with the transferrin saturation to accurately diagnose ID.

Reference values for reticulocyte haemoglobin equivalent in healthy Chinese children under 5 years and its associations with various blood parameters

BackgroundReticulocyte haemoglobin equivalent (RET-He) is a useful tool for evaluating recent iron usage irrespective of inflammatory status. This study aims to establish a reference for RET-He among Hong Kong healthy...

Correlation Between RET-He and Quality of Life in Chronic Kidney Disease Patients with Routine Hemodialysis: A Study at Ulin General Hospital Banjarmasin

Background: The 2018 Riskesdas report revealed that the incidence of chronic kidney disease (CKD) affects 0.38% of Indonesia’s population. Anemia frequently complicates CKD, especially in patients undergoing regular hemodialysis. Reticulocyte hemoglobin equivalent (RET-He) assesses hemoglobin content in reticulocytes, indicating iron availability for erythropoiesis in the bone marrow. CKD significantly impacts patients' socio-economic status, heightening morbidity and mortality while diminishing quality of life. The relationship between RET-He and the quality of life in CKD patients on routine hemodialysis remains unclear. Objective: To investigate the correlation between RET-He and quality of life in CKD patients undergoing routine hemodialysis. Methods: A cross-sectional observational analytical study with data from medical records of CKD patients receiving routine hemodialysis between October 1st and October 30th, 2021. The Spearman correlation test was used for analysis. Results: This study included 92 patients, consisting of 40 males and 52 females, with a median age of 50 years and RET-He values at 31. Quality of life metrics included physical function (800, range: 0-1000), physical limitations (300, range: 0-400), body pain (175, range: 75-255), general health (475, range: 225-600), vitality (320, range: 200-400), social function (175, range: 75-200), emotional limitations (300, range: 100-300), and mental health (380, range: 160-500). The correlation analysis revealed no significant relationships: physical function (p=0.359), physical limitations (p=0.813), body pain (p=0.373), general health (p=0.547), vitality (p=0.616), social function (p=0.828), emotional limitations (p=0.482), and mental health (p=0.136). Conclusion: There is no significant correlation between RET-He levels and the quality of life in CKD patients undergoing regular hemodialysis.

The role of reticulocyte hemoglobin equivalent on the evaluation of iron deficiency and iron deficiency anemia in pediatric cyanotic heart disease: a diagnostic study in Indonesia

BackgroundIn light of prolonged hypoxia, children with cyanotic heart disase (CHD) are at a high risk of developing iron deficiency iron deficiency (ID) and iron deficiency anemia (IDA). Reticulocyte hemoglobin equivalent (Ret-He) is a novel and dependable indicator for assessing iron status. However, there has been no previous study regarding cut-off value in pediatric CHD group. The purpose of this study is to assess the role of Ret-He and to establish cut-off points in the diagnosis of iron deficiency and IDA in pediatric cyanotic heart disease.MethodThis study was conducted in two tertiary hospitals in Jakarta, Indonesia. 59 children with CHD, aged 3 months to 18 years, were enrolled consecutively. To determine iron status, hematological parameters (hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin) and biochemical parameters for iron status (serum ferritin, transferrin saturation) were analysed and compared to Ret-He levels. The receiver operating characteristic (ROC) analysis was performed for the Ret-He cut-off points for ID and IDA. Sensitivity, specificity, positive and negative predictive value were calculated for each cut-off point.ResultNormal iron status was identified in 27 (45.8%) subjects, ID in 8 (13.5%) subjects, and IDA 24 (40.7%) subjects. The ID cut-off value for Ret-He is 28.8 pg (sensitivity 75%, specificity 85.2%, PPV 60%, NPV 92%, and AUC 0.828) and the Ret-He cut-off point for IDA is 28.15 pg (sensitivity 75%, specificity 88.9%, PPV 85.7%, NPV 80%, and AUC 0.824). Hemoglobin should be used in conjunction with Ret-He. ID might be detected in this cohort with Ret-He 28.8 pg and hemoglobin > 16,5 g/dL. While Ret-He 28.15 pg or Ret-He 28.15–28.8 pg with hemoglobin 16.5 g/dL could be used to diagnose IDA.ConclusionThe reticulocyte hemolgobin equivalent could be utilised as an iron status parameter in pediatric CHD, with a cut-off value of 28.8 pg for ID and 28.15 pg for IDA.

Utility of reticulocyte haemoglobin content (CHr) in the diagnosis of iron deficiency anaemia in adult females

Utility of reticulocyte haemoglobin content (CHr) in the diagnosis of iron deficiency anaemia in adult females

Efficacy of Reticulocyte Hemoglobin Content and Immature Reticulocyte Fraction in Early Diagnosis of Latent Iron Deficiency in Blood Donors

Efficacy of Reticulocyte Hemoglobin Content and Immature Reticulocyte Fraction in Early Diagnosis of Latent Iron Deficiency in Blood Donors

#2898 Exposure response model describing hematologic changes with chronic treatment of CKD anemia with vadadustat

Abstract Background and Aims Vadadustat (VADA) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate endogenous erythropoietin production, increasing iron mobilization and red blood cell production. VADA is approved in 36 countries globally and is indicated in the European Union for the treatment of symptomatic anaemia associated with chronic kidney disease (CKD) in adults on chronic maintenance dialysis and is an alternative to treatment with erythropoiesis-stimulating agents (ESAs). The aim of this work was to develop a predictive, semi-mechanistic model to understand the effects of VADA and erythropoiesis-stimulating agents (ESAs) on hemoglobin response and to evaluate the impact of intrinsic and extrinsic patient characteristics on that response for non-dialysis dependent (NDD) and dialysis-dependent (DD) patient populations. Method A predictive semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model for VADA and ESA treatment was developed using nonlinear mixed effects methods. The model describes changes in reticulocyte count (RETICs), mature erythrocytes (RBCs) and hemoglobin (Hb) as a function of drug exposure and subject-specific characteristics. The dataset was based on data from 7 Phase 1 to Phase 3 studies (Table 1; N = 894 for VADA; N = 560 for ESA modeling) in healthy volunteers and subjects with NDD- or DD-CKD who were either ESA-naïve or ESA experienced but not receiving treatment at screening. Prior population PK modeling of VADA provided estimated drug exposures for VADA-treated subjects, while dose normalized to standard units (IU/kg/wk) was used as the exposure metric for subjects on ESA. Each of these exposure metrics could vary with time, as the dose was adjusted according to observed Hb response. This work evaluated alternative model structures, as well as covariate effects affecting Hb individual response. Results A predictive semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model for VADA and ESA treatment was developed using nonlinear mixed effects methods. The model describes changes in reticulocyte count (RETICs), mature erythrocytes (RBCs) and hemoglobin (Hb) as a function of drug exposure and subject-specific characteristics. The dataset was based on data from 7 Phase 1 to Phase 3 studies (Table 1; N = 894 for VADA; N = 560 for ESA modeling) in healthy volunteers and subjects with NDD- or DD-CKD who were either ESA-naïve or ESA experienced but not receiving treatment at screening. Prior population PK modeling of VADA provided estimated drug exposures for VADA-treated subjects, while dose normalized to standard units (IU/kg/wk) was used as the exposure metric for subjects on ESA. Each of these exposure metrics could vary with time, as the dose was adjusted according to observed Hb response. This work evaluated alternative model structures, as well as covariate effects affecting Hb individual response. A similar model structure was found to describe early changes in RETICs and longer-term changes in Hb for both VADA and ESAs. In each case, the magnitude of response increases with increased drug exposure up to a maximum value (Emax), and the Emax values were similar between VADA and ESAs. Subject intrinsic predictors of response included eGFR, subject age, BMI, and serum albumin, while extrinsic factors affecting response included geographic region, limits on acceptable Hb values (which also differ by geographic region) and the presence of previous ESA treatment. Interestingly, Hb responses were also correlated with changes in serum hepcidin, a key regulator of iron homeostasis, following both VADA and ESA treatment. Differences between the response to VADA and ESA were also described, including differences in temporal changes in RETICs and Hb. Conclusion This model showed an exposure-response relationship between VADA or ESA treatment and changes in RETICs and Hb for ESA naïve or ESA-experienced CKD subjects. The model will be used to inform dosage recommendations for VADA based on patient characteristics.

Current approach to the management of preoperative iron deficiency anemia in colorectal cancer patients: a review of literature.

&lt;b&gt;Introduction:&lt;/b&gt; The prevalence of preoperative anemia is the highest in the group of colorectal cancer (CRC) patients and may reach over 75%. The prevalence of anemia in CRC patients increases even further following surgery. Approximately 75-80% of anemic CRC patients present with absolute or functional iron deficiency (ID). Preoperative anemia constitutes an independent risk factor for allogeneic blood transfusion (ABT), postoperative complications, prolonged length of hospital stay, and increased mortality. ABT is itself associated with increased morbidity and mortality.&lt;b&gt;Aim:&lt;/b&gt; The aim of this review article was to present the pathophysiology and the current approach to the diagnostics and treatment of preoperative iron deficiency anemia (IDA) in CRC patients.&lt;b&gt;Material and methods:&lt;/b&gt; Extensive search of medical literature databases was performed (Pubmed, Embase). The key words that were used were as follows: CRC, colorectal surgery, ID, IDA, intravenous iron, Patient Blood Management (PBM).&lt;b&gt;Results:&lt;/b&gt; There are several laboratory parameters that can be used for IDA diagnosis, however, the simplest and most cost- -effective is reticulocyte hemoglobin equivalent (RET-He). Pathophysiologic features of IDA in CRC patients favor treatment with intravenous, as opposed to oral, iron formulations. Applying PBM strategies minimizes the exposure to ABT.&lt;b&gt;Conclusions:&lt;/b&gt; Preoperative IDA is highly prevalent among CRC patients. Preoperative anemia is an independent risk factor for ABT, increased morbidity and mortality, as well as prolonged hospital length of stay. The same negative consequences are associated with ABT. Therefore, preoperative IDA in CRC patients needs to be screened for, diagnosed, and treated before surgery. Effective treatment of preoperative IDA in CRC patients is with intravenous iron formulations. ABT should be the treatment of last resort due to the risk of negative clinical consequences, including an increased rate of cancer recurrence.

Imbalance of Iron Availability and Demand in Patients With Acute and Chronic HeartFailure.

Iron deficiency (ID) is a frequent comorbidity in patients with acute (AHF) and chronic heart failure (CHF) associated with morbidity and death. We aimed to better characterize iron homeostasis in patients with heart failure applying different biomarkers and to evaluate the accuracy of current ID definition by the European Society of Cardiology/American College of Cardiology/American Heart Association to indicate tissue iron availability and demand. We performed a retrospective cohort study investigating 277 patients with AHF and 476 patients with CHF between February 2021 and May 2022. Patients with AHF had more advanced ID than patients with CHF, reflected by increased soluble transferrin receptor and soluble transferrin receptor-ferritin index, and lower ferritin, serum iron, transferrin saturation, hepcidin, and reticulocyte hemoglobin. Decreased iron availability or increased tissue iron demand, reflected by increased soluble transferrin receptor-ferritin index and decreased reticulocyte hemoglobin, was found in 84.1% (AHF) and 28.0% (CHF) with absolute ID and in 50.0% (AHF) and 10.5% (CHF) with combined ID according to the current European Society of Cardiology/American College of Cardiology/American Heart Association-based ID definition. Low hepcidin expression as an indicator of systemic ID was found in 91.1% (AHF) and 80.4% (CHF) of patients with absolute ID and in 32.3% (AHF) and 18.8% (CHF) of patients with combined ID. ID definitions with higher specificity reduce the need for iron supplementation by 25.5% in patients with AHF and by 65.6% in patients with CHF. Our results suggest that the current European Society of Cardiology/American College of Cardiology/American Heart Association-based ID definition might overestimate true ID, particularly in CHF. More stringent thresholds for ID could more accurately identify patients with heart failure with reduced tissue iron availability who benefit from intravenous iron supplementation.

Iron Indices Mediate but Not Modify Association of Parathyroid Hormone with Erythropoietin Resistance in Hemodialysis Patients

Introduction: Disordered iron balance and abnormal parathyroid hormone (PTH) concentrations, both prevalent in hemodialysis patients, are risk factors of erythropoietin (EPO) resistance. Few studies have evaluated the correlation between iron indices and PTH and the potential role of iron markers on the association of PTH with EPO resistance in hemodialysis population. Methods: In this cross-sectional study of 71 maintenance hemodialysis patients, iron indices including hepcidin, ferritin, reticulocyte hemoglobin content (CHr), and transferrin saturation (TSAT) were examined. EPO responsiveness was measured as EPO resistance index (ERI). Lowess regression curves were performed to explore the correlations of iron indices, PTH, and ERI. The association between PTH and ERI was modeled using linear regressions. Potential role of iron indices on this association was examined using stratified analyses and mediation analyses. Results: The average ERI value was 10.3 ± 5.3 IU w−1 kg−1 (g/dL) −1. ERI was correlated to PTH, hepcidin, CHr, and TSAT (all p < 0.05). Hepcidin and PTH were closely correlated with each other (r = 0.28, p = 0.020). Analysis by PTH categories yielded a total association effect of 2.53 (95% CI: 0.27–4.85, p = 0.027) for high PTH subgroup versus the reference low subgroup. No clinically significant interaction between iron indexes and PTH was identified. Hepcidin appeared to mediate about one-third of the total association between PTH and ERI in hemodialysis population (33.6%, p = 0.025). Conclusion: Iron indices and PTH levels were related to ERI values. Hepcidin appeared to be closely correlated to PTH and partly mediate the association between PTH and ERI in hemodialysis population.