Reticulocyte Hemoglobin Research Articles

Association between Pre-Infusion Laboratory Characteristics and Hematologic Response in Patients Treated for Iron-Deficiency at a Tertiary Care Center

Background :A panel of laboratory tests are used to diagnose iron deficiency anemia, including hemoglobin (Hb), mean cell volume (MCV), serum ferritin, total iron binding capacity (TIBC), and iron saturation (ISAT). Newer diagnostic biomarkers include reticulocyte hemoglobin (RHb). The association between these parameters and response to intravenous iron have not been well characterized. The aim of this study was to evaluate the associations between baseline laboratory values commonly used in diagnosis of iron-deficiency anemia and improvement in hemoglobin concentration (Hb). Methods :Data was collected retrospectively using The Ottawa Hospital Data Warehouse (OHDW) reflecting practices from 3 local institutions. Patients that received at least 1 intravenous iron infusion between 2007 and 2018 were included. Patients that received intravenous iron replacement with baseline hemoglobin and at least one hemoglobin measured after the last documented iron infusion were included. Patients transfused within 90 days of the last infusion were excluded. For patients that received more than one course of iron replacement, each course was included separately if the time between the last infusion of the earlier course and the first infusion of the later course were at least 180 days apart. The primary outcome was achieving a maximum change in Hb of ≥10 g/L after the last iron infusion. Logistic regression was used to measure the association between pre-infusion laboratory characteristics (Hb, mean cell volume [MCV], platelet and reticulocyte count, reticulocyte Hb, ferritin, total iron binding capacity [TIBC], and iron saturation [ISAT]), age, sex, and presence of chronic kidney disease (CKD[serum creatinine >177 µmol/L]) and the primary outcome. A multivariable logistic regression model was used to adjust for baseline characteristics and the primary outcome, adjusting for iron replacement characteristics. Results :Between 2007 and 2018, a total of 8326 patients were treated with intravenous iron replacement, of whom 7185 were not transfused 90 days before the last administered dose of iron. Baseline characteristics of these patients are summarized in Table 1. The median maximum post-infusion hemoglobin was 119 g/L (interquartile range [IQR] 107-30 g/L), with a median change from pre-infusion hemoglobin of 16 g/L (IQR 5-31). The maximum Hb was measured a median of 62 days (IQR 6-144 days) after the last infusion. Results of univariable (Table 2) and multivariable (Table 3) regression are shown in Tables 2 and 3, respectively. In the multivariable model, pre-infusion Hb was the only evaluated laboratory value associated with Hb response (OR 0.48 95% confidence interval (95%CI) 0.38-0.62, p<0.001). Presence of CKD (OR 0.35, 95%CI 0.19-0.66, p=0.001) and the number of infusions given per course (OR 1.33, 95%CI 1.15-1.53, p<0.001) were also associated with hematologic response. Conclusions:In this single-center, retrospective cohort of patients treated with intravenous iron replacement and not transfused red blood cells within 90 days of the last infusion, most evaluated baseline characteristics were not associated with achieving a ≥10 g/L improvement in Hb concentration. Baseline Hb concentration was associated with Hb response, with higher baseline Hb associated with a lower probability of a 'good' Hb response. The presence of CKD was also associated with lower chance of hematologic response. The study has several important limitations including the lack of diagnostic data relating to the need for iron infusions, concomitant oral supplementation, and potential infusions outside the study site. Pre-infusion laboratory values were missing for a large proportion of patients. The strengths of the study include the large sample size and broad inclusion criteria, allowing for increased generalizability. Further exploration of serum biomarkers in the prediction of hemoglobin responses in parenteral iron supplementation is warranted in prospective studies with scheduled laboratory measurements. Disclosures No relevant conflicts of interest to declare.

Hepatobiliary Manifistations of COVID-19 in Sickle Cell Disease: A Case Report

Hepatobiliary manifestation of COVID-19 in Sickle Cell Disease: A Case report.Background and aim:SARS-CoV-2 belongs to the Coronaviridae family, and the virus began spreading worldwide in late December 2019. It mainly affects the respiratory system. However, some studies have shown an increasing number of patients reporting gastrointestinal manifestations associated with COVID-19. There is little clinical experience of COVID‐19 patients with sickle cell disease (SCD) especially in our country, and most reported cases presented with acute chest syndrome (ACS). Sickle cell hepatopathy is common and ranges from benign hyperbilirubinemia and biliary sludge to overt liver failure, but it is unclear how this is affected by COVID-19.Case presentation:We report a case of a 5-year-old Saudi, non-obese female who was diagnosed as sickle B+ thalassemia (HbS: 71.9%, HbA 1.4%, HbA2: 6 & HbF: 20.7%) and was on hydroxyurea, folic acid, and vitamin D. The child came to our Emergency Department on 28/7/2020 with a one-week history of generalized abdominal pain related to the food ingestion and associated with vomiting and diarrhea. There is a history of jaundice, dark urine, and clay-like stool. There was no documented fever, history of cough, or respiratory distress. There was a history of contact with Covid-19 patient. On clinical examination, the child was vitally stable but jaundiced. She was in pain with tenderness over the right part of the abdomen but no organomegaly; other systematic examinations were normal. Her initial laboratory finding showed elevated liver enzyme (ALT: 148U/L, AST: 89U/L, GGT:150U/L, ALP:149U/L) with direct hyperbilirubinemia (total bilirubin 4.5mg/dl and direct bilirubin 2.6 mg/dl), high reticulocyte, and stable hemoglobin (10 mg/dl). She had a normal leukocyte count, platelet count, inflammatory markers, and pancreatic enzymes. Her abdominal U/S showed no hepatic focal lesions detected with normal size liver and no evidence of intrahepatic bile duct dilatation. In addition, the common bile duct and the portal vein were not dilated. The gallbladder showed normal wall thickening and was partially filled with sludge without stones (Figure 1).The child was kept on diet restriction and treated with maintenance intravenous fluid (IVF) and paracetamol. Hydroxyurea was stopped. Her gastrointestinal manifestations improved, and the liver enzymes subsided within days (Figure 2). After four days, the child was discharged home. Two days later, she was readmitted with poor oral intake and generalized upper limb pain (vaso-occlusive crisis). There was no clinical finding on examination. Her laboratory finding was acceptable, and she was started on IVF and analgesia. On 8/8/2020, she was discharged in very good clinical condition.Conclusions:It is clear that COVID-19 has significant impact on SCD. Poor oral intake that associated with viral infection can cause biliary sludge and Close follow-up is essential for those patients. Further studies are needed to support this finding.DisclosuresNo relevant conflicts of interest to declare.

Administration of KER-047, a Novel ALK2 Inhibitor, Elicited Robust and Sustained Increases in Serum Iron in Healthy Participants

Background: Hepcidin is the master regulator of iron homeostasis. Its expression is controlled, in part, by signaling through TGF-β receptors including activin receptor-like kinase-2 (ALK2). As part of a negative feedback loop, high hepcidin levels increase expression of matriptase-2, which cleaves the ALK2 co-receptor hemojuvelin from the cell surface and suppresses ALK2 signaling. Dysregulation of the negative feedback system results in high hepcidin, which mobilizes iron from storage tissues and leads to insufficient iron for red blood cell production in the bone marrow, resulting in anemia. KER-047 is a selective ALK2 inhibitor that has the potential to normalize ALK2 signaling and the downstream sequalae that results in anemia as a result of elevated hepcidin. Aims: The objective of this Phase 1 study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending dose levels of KER-047 in healthy participants. Methods: In Part 1, two formulations of KER-047 were evaluated in single ascending oral doses ranging from 1 mg to 300 mg of a capsule formulation, and 30 mg to 450 mg of a liquid formulation or placebo. In Part 2, the liquid formulation was evaluated in multiple ascending doses (50 mg, 100 mg, 200 mg and 350 mg) of KER-047 or placebo, administered daily for up to 7 days. Endpoints included adverse events (AEs) and pharmacokinetic and pharmacodynamic parameters. Informed consent was obtained from all participants prior to enrollment in the study. Results: Part 1 enrolled 80 participants; 60 received a single dose of KER-047 and 20 received placebo. Part 2 enrolled 41 participants; 32 received KER-047 and 9 received placebo daily for up to 7 days. There were no serious adverse events in either part of the study. In Part 1, 3 (9.4%) participants discontinued the study; none discontinued due to AEs. In Part 2, 3 (9.4%) participants administered KER-047 and 1 (11.1%) placebo discontinued the study; of these, 2 participants discontinued due to an AE (one in the 200 mg group and one on placebo). In Part 2, 1 of 8 (12.5%) administered 200 mg and 4 of 8 (50%) participants administered 350 mg discontinued study drug due to AEs. The majority of AEs observed in participants administered KER-047 were mild or moderate in severity; severe AEs were reported only at the 350 mg multiple dose in 1 of 8 (12.5%) participants. AEs reported in ≥2 of participants administered KER-047 and higher than placebo were: headache, nausea, vomiting, diarrhea, gastroenteritis, chills, pyrexia, myalgia, decreased appetite, lymphopenia, neutropenia, and liver enzyme increases. Decreases in lymphocyte and neutrophil counts were observed at 200 mg and 350 mg. Mean KER-047 AUC and Cmax increased linearly, with greater than dose-proportional increases observed across multiple doses from 50-200 mg. Half-life values ranged from approximately 10 to 15 hours. Administration of KER-047 elicited rapid, robust and sustained dose-related increases in serum iron and transferrin saturation. Increases in serum iron and transferrin saturation were observed beginning on Day 2 after single doses and were sustained after multiple doses. Decreases in ferritin were also observed. Decreases in serum hepcidin post-dose were also observed in all the multiple dose cohort in which changes were evaluated. Reticulocyte hemoglobin content increased starting on Day 3 post-dosing indicating increased iron availability in the bone marrow. Summary: In healthy participants, administration of KER-047 elicited rapid, robust and sustained dose-related increases in serum iron and transferrin saturation that were associated with decreases in ferritin and hepcidin. The observed decrease in ferritin and hepcidin coupled with increases in reticulocyte hemoglobin content are indicative of increased iron mobilization, resulting in increased iron incorporation into hemoglobin. The tolerability profile of KER-047 in healthy participants has been characterized in this Phase 1 study. KER-047's unique pharmacologic effect on hepcidin and iron mobilization has the potential to treat anemia that results from elevated hepcidin. Table Disclosures Ordonez: Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company; Ackea Therapeutics: Ended employment in the past 24 months. Ben:Nucleus Network: Current Employment. Barger:Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company. Serino:BioBridges: Ended employment in the past 24 months; Keros Therapeutics: Current Employment. Tseng:Mitobridge: Current equity holder in private company; Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Rovaldi:Keros Therapeutics: Consultancy. Lachey:Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company. Seehra:Keros Therapeutics: Current Employment, Current equity holder in publicly-traded company.

Reticulocyte hemoglobin equivalent as a diagnostic marker for the current iron deficiency

Reticulocyte hemoglobin equivalent as a diagnostic marker for the current iron deficiency

The measurement of reticulocyte hemoglobin content: a modern approach to the diagnosis of iron deficiency in children

Iron deficiency is one of the most widely spread types of microelementosis, especially in a growing organism. It is essential to diagnose iron deficiency at an early stage in order to start treatment timely. Diagnostics of iron deficiency can be complicated by concomitant diseases that distort biochemical parameters of iron metabolism, thus making them not informative enough. In this connection, hemoglobin count in reticulocytes (Ret-Hb) and delta-hemoglobin (Delta-He) may be useful indicators as they help to diagnose true iron deficiency at earliest stages and do not depend on concomitant conditions, which is described in reference sources. In this work, Ret-Hb and Delta-He were detected in the structure of blood hematology test performed on hematology analyzers Sysmex XT-4000 and Sysmex XN-9000 (Japan) in 24 children aged 1–18 with absolute iron deficiency; three of these children had absolute iron deficiency manifested as latent deficiency, and 19 children had hypochromic microcytic anemia of mild or medium severity. The parameter was below the normal limit (the average count was 24.2 ± 3.5 pg), while the normal limit is 28 pg, according to the reference sources. After two weeks of treatment, Ret-Hb increased up to 26.0 ± 2.9 pg. Delta-He, being initially as low as 2.9 ± 0.9 pg (with the lower threshold of 4.0 pg) rose up to 6.3 ± 3.4 pg. The results of our research have demonstrated that Ret-Hb and Delta-He may be regarded as informative, economical and affordable diagnostic parameters that do not require collection of additional blood samples. Their dynamics during treatment should be investigated further. This study was approved by the Independent Ethics Committee and the Scientific Council of Saint Petersburg State Pediatric Medical University of Ministry of Healthcare of the Russian Federation.

Serum hepcidin concentrations in relation to iron status in children with type 1 diabetes

Chronic low-grade inflammation in type 1 diabetes (T1D) might increase hepcidin synthesis, possibly resulting in functional iron deficiency (FID). We hypothesized that in T1D children with FID, hepcidin concentrations are increased compared to those with normal iron status and those with absolute iron deficiency (AID). We evaluated hepcidin concentrations in T1D children in relation to iron status, and investigated whether hepcidin is useful in assessing FID. A cross-sectional study was conducted. FID was defined as elevated zinc protoporphyrin/heme ratio and/or red blood cell distribution width, and AID as low serum ferritin concentration. Post-hoc analyses with different definitions of FID were performed, using transferrin saturation and reticulocyte hemoglobin content. Serum hepcidin concentrations were measured using mass-spectrometry. The IRODIAB-study is registered at www.trialregister.nl (NTR4642). This study included 215 T1D children with a median age of 13.7 years (Q1–Q3: 10.1–16.3). The median (Q1–Q3) hepcidin concentration in patients with normal iron status was 1.8 nmol/l (0.9–3.3), in AID-patients, 0.4 nmol/l (0.4–0.4) and in FID-patients, 1.6 nmol/l (0.7–3.5). Hepcidin concentrations in FID-patients were significantly higher than in AID-patients (p < 0.001). Irrespective of FID-definition used, hepcidin concentrations did not differ between FID-patients and patients with normal iron status. This might be explained by the influence of various factors on hepcidin concentrations, and/or by differences in response of iron parameters over time. Single hepcidin measurements do not seem useful in assessing FID in T1D children. Multiple hepcidin measurements over time in future studies, however, might prove to be more useful in assessing FID in children with T1D.

Reconciling markedly discordant values of serum ferritin versus reticulocyte hemoglobin content.

To determine why serum ferritin and reticulocyte hemoglobin (RET-He), drawn to assess neonatal iron sufficiency, sometimes have markedly discordant results. Retrospective records review of five NICUs over 28 months, identifying all patients with a ferritin and RET-He within 48 h. We examined records of all who had marked discordance (one value >95th % reference interval, the other <5th %). Of 190 paired ferritin and RET-He measurements, 16 (8%) were markedly discordant. Fifteen of the 16 discordant samples involved a high ferritin and a low RET-He. In these, low MCV and high %Micro-R, and low MCH and high %HYPO-He were present. In total, 8 of the 15 had laboratory or clinical evidence of an inflammatory process and five had suspicion of infection documented. When ferritin and RET-He were discordant, erythrocyte microcytosis and hypochromasia suggested that the RET-He gave the more accurate interpretation; that iron deficiency was likely present.

The difference of Reticulocyte Hemoglobin Equivalent Pre- and Post-Ultrafiltration Hemodialysis in Patients with Chronic Kidney Disease

Chronic Kidney Disease (CKD) is a condition characterized by kidney damage and a decrease of Glomerular Filtration Rate of less than 60 mL/ min/1.73 m2 in more than three months. Anemia is the most common complication in patients with CKD who regularly undergo hemodialysis. Reticulocyte Hemoglobin Equivalent (Ret-He) is a new parameter that can reflect the storage of iron for erythropoiesis. This study compared the Ret-He level pre and post-hemodialysis and evaluated the effect of ultrafiltration (UF) hemodialysis to Ret-He level in CKD patients. This research was an observational analytical study. Samples were 50 patients with CKD who underwent hemodialysis regularly in Dr. Soetomo Hospital Surabaya by consecutive sampling from August–September 2017. The measurement of the Ret-He level pre ultrafiltration hemodialysis was divided into UF &lt; 2 L and UF ≥ 2 L. Both groups showed homogenous results. The group with UF &lt; 2 L increased significantly from pre to post ultrafiltration (p=0.010). The group with UF ≥ 2 L was not increased considerably from 30.57±3.62 to 32.69±3.45 (p=0.413). Ret-He level in the group with UF &lt; 2 L was 0.81±1.10, significantly higher than the group with UF ≥ 2 L 0.12±0.83 (p=0.017). The difference of Ret-He level pre and post ultrafiltration was significant in UF &lt; 2 L. There was a significant increase of the Ret-He level in hemodialysis with UF &lt; 2 L compared to UF ≥ 2 L. The measurement of Ret-He should be performed before hemodialysis due to an increase in Ret-He after ultrafiltration hemodialysis.

A Hypoxia-Inducible Factor Stabilizer Improves Hematopoiesis and Iron Metabolism Early after Administration to Treat Anemia in Hemodialysis Patients.

Roxadustat (Rox), a hypoxia-inducible factor (HIF) stabilizer, is now available for the treatment of anemia in hemodialysis (HD) patients. To investigate hematopoietic effect and iron metabolism, this study involved 30 HD patients who were initially treated with darbepoetin (DA), a conventional erythropoietin-stimulating agent, and then switched to Rox. We measured erythrocyte, reticulocyte indices, and iron-related factors at every HD during the first two weeks after the treatment switch (Days 0–14) and again on Days 21 and 28. We measured erythropoietin (EPO) concentration every week and examined their changes from Day-0 values. The same variables were measured in 15 HD patients who continued DA at every HD for one week. Iron-related factors were also measured on Days 14 and 28. In the Rox group, hepcidin significantly decreased from Day 2. The reticulocyte hemoglobin content (CHr) significantly increased on Day 4, but decreased with a significant increase in reticulocyte count from Day 7. Log10(serum ferritin) significantly decreased after Day 11. Log10(EPO concentration) was lower at all time points. Compared with the DA group, the Rox group showed significant differences in all variables except CHr. These results suggest that Rox improves hematopoiesis and iron metabolism early after administration independent of EPO concentration.

Assay for "fetal hemoglobin levels" in erythrocytes: Impact of new In Vitro Diagnostics regulation and expanded applications in sickle cell disease management.

Assay for "fetal hemoglobin levels" in erythrocytes: Impact of new In Vitro Diagnostics regulation and expanded applications in sickle cell disease management.

Reticulocyte hemoglobin concentration for screening iron deficiency in very low birth weight preterm neonates

Background Preterm and low birth weight infants are at risk of iron deficiency. Reticulocyte hemoglobin concentration may be useful as a screening test to diagnose iron deficiency in preterm neonates. Objective To evaluate the accuracy and establish the reticulocyte hemoglobin concentration cutoff value for iron deficiency diagnosis in very low birth weight preterm neonates. Method This study was conducted between May 2018 and March 2019 at Chiang Mai University Hospital. Preterm infants born at gestational age ≤34 weeks and birth weight ≤1500 g were enrolled. Blood samplings were obtained within the first 48 h of life. Iron deficiency was defined by using two or more of these following parameters: mean corpuscular volume <100 fL, transferrin saturation <16% and serum ferritin <30 µg/L. Neonatal anemia was defined as hemoglobin <15 g/dL. The optimum reticulocyte hemoglobin concentration cutoff values were performed by using predictive values and receiving operation characteristic analysis. Result Fifty-seven preterm neonates were enrolled. Nine (15.7%) and three (5.3%) neonates had iron deficiency and iron deficiency anemia, respectively. The reticulocyte hemoglobin concentration cutoff value of <29 pg showed the optimum accuracy to diagnose iron deficiency in very low birth weight preterm neonates with sensitivity, specificity, positive and negative predictive values of 89%, 79%, 42% and 97%, respectively. Conclusion Reticulocyte hemoglobin concentration can be used as a screening parameter to diagnose iron deficiency for VLBW preterm neonates. The optimum cutoff value which provided the acceptable accuracy was <29 pg.

The Role of Reticulocyte Hemoglobin Content for the Diagnosis of Functional Iron Deficiency in Hemodialyzed patients.

The effectiveness of reticulocyte hemoglobin content (CHr) had been reported to detect early functional iron deficiency especially among Chronic kidney disease (CKD) patients. CHr is more superior to classic biochemical indices in reflecting transient iron-deficiency status, therefore improving diagnosis and treatment. This study was conducted to determine the sensitivity of CHr in the diagnosis of functional iron deficiency (FID) in hemodialyzed patients. One hundred hemodialyzed patients along with 60 healthy controls were recruited and blood specimens were collected. Venous blood was used for hematological and biochemical investigations collected via 3 ml lavender-top tubes for hematological tests including CBC, blood film, ESR and CHr, and red-top tube for biochemical tests including TIBC, SF and CRP. A statistically significant decrease was noted in CHr values between hemodialysis patients and the control group (24.8 ± 2.0 pg vs. 30.9 ± 1.3 pg, p<0.001). CHr values showed a significant correlations with RBCs, Hb- hemoglobin, Hct- hematocrit level, MCV- mean corpuscular volume, MCH- mean corpuscular hemoglobin, MCHC, RDW- red cell distribution width , SI-Serum Iron, TIBC- Total iron binding capacity and TSAT- Transferrin saturation. The present study showed that CHr in comparison to the conventional hematological and biochemical markers commonly used to diagnose iron deficiency.

Diagnostic work up of anemic patients: role of iron deficiency

Abstract Objectives Diagnosing 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. Methods Patients 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. Results A 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. Conclusions The 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.

Immature cell fractions after cessation of chronic P2Y12-inhibition in patients with coronary artery diseases

Changes in circulating cell populations may promote ischemic events that occur soon after discontinuation of P2Y12-inhibition. The aim of the study was to track the course of thrombopoietic and erythropoietic cells in patients with coronary artery diseases (CAD) after planned and physician-driven cessation of chronic P2Y12-inhibition (clopidogrel 75 mg OD, or prasugrel 10 mg OD, or ticagrelor 90 mg BID). Cell fractions were determined in 62 patients at baseline (the last day of P2Y12-inhibitor intake), on day-10, day-30, and day-180 thereafter. Immature platelet fraction (IPF), immature reticulocyte fraction (IRF), reticulocyte hemoglobin content (Ret-Hb) and red blood cell count (RBC) significantly increased from baseline to day-180 (IPF: p = .003; IRF: p = .013; Ret-Hb: p < .001; RBC: p = .044). Platelet count, leucocyte count and immature granulocyte fraction did not change over time (p = .561, p = .869, and p = .161, respectively). Fibrinogen levels significantly declined over time (p = .011), thrombopoietin levels increased in a non-significant manner (p = .379). We did not observe any significant interaction with choice of P2Y12-inhibitor, therefore suggesting a drug class-effect. Our data shows, that discontinuation of dual antiplatelet therapy is associated with raised thrombopoietic and erythropoietic activity in the bone marrow, without significant upregulation of thrombopoietin. This provides further evidence for a direct stimulation of precursor cells by P2Y12-inhibitors.

Diagnostic value of reticulocyte hemoglobin equivalent to confirm iron deficiency in full-term infants

Diagnostics of Iron deficiency anemia (IDA) in outpatient pediatric practice is often based on decreased hemoglobin level. Latent iron deficiency diagnostic is not a part of current routine practice.Objective. To study the diagnostic value of red blood cell indices and reticulocyte hemoglobin equivalent in diagnostics of iron deficiency in full-term infants.Children characteristics and research methods. A prospective cohort study of healthy full-term children aged from 6 to 12 months at the children hospitals of Samara and Tolyatti. The laboratory examination included a general blood test to determine the concentration of hemoglobin, the number of red blood cells, red blood cell indices, and reticulocyte hemoglobin equivalent (Ret-He); to determine serum ferritin and C-reactive protein. The AUC (area under the curve) was used to determine the diagnostic value of quantitative indicators. The children with anemia without iron deficiency and children who received iron supplements within 1 month prior to laboratory examination were excluded from the analysis.Results. The study involved 207 children. When diagnosing iron deficiency in children, the highest AUC was found in Ret-He: 0.747 [0.679; 0.816] in 6-months-old children and 0.790 [0.708; 0.871] in 1-year-old children. The Ret-He diagnostic value was higher in children with iron deficiency: AUC 0.826 [0.754; 0.898] in 6- months-old children and 0.865 [0.809; 0.920] in 1-year-old children.Conclusion. Ret-He is a better predictor of iron deficiency in children under 1 year as compared to the red blood cell indices. The diagnostic value of red blood cell indices and Ret-He is higher in case of iron deficiency anemia than in case of iron deficiency conditions.

Evaluation of Reticulated Haemoglobin (CHr) as a diagnostic parameter in Iron Deficiency Anemia

Introduction: Iron deficiency anemia (IDA) is the commonest nutritional deficiency in all parts of the world. In developing countries, the commonest cause is inadequate dietary intake [1]. The red cell indices raise the suspicion of iron deficiency state due to the microcytic, hypochromic changes and the wide red cell distribution width. The iron studies are confirmatory of an iron deficiency state, but are not accurate in the presence of infection, inflammation or malignancy as they are acute phase proteins and are affected in these states making the serum iron studies unreliable under these conditions. The reticulocyte haemoglobin content (CHr) indicates the iron available in the marrow for the production of Hb and are not affected by the above-mentioned situations and therefore has been recommended as a reliable marker of iron status in the body. The value for CHr given in the literature was 25pg [3].&#x0D; Objectives: General objective was to evaluate the significance of CHr in the diagnosis of IDA. The Specific objectives were to compare CHr with the other conventional iron parameters including serum iron, serum ferritin, TS and TIBC and evaluate any significance of CHr with RBC indices (MCV, MCH and MCHC) and age.&#x0D; Methodology: A retrospective analytical study performed at the Department of Haematology of a Tertiary care hospital in Sri Lanka. Data was obtained from the patient records of those referred to the Haematology department for management of iron deficiency during the period of 9 months commencing from April 2019 to January 2020. Data from 178 adult patients both males and females (16 to 84 years) diagnosed with IDA (S. Ferritin &lt; 20ng/ml) (Hb &lt; 12g/dl in men and Hb &lt;11.5g/dl in women) were randomly selected. In pregnant females the S. Ferritin level considered was &lt;30ng/ml and the Hb level was &lt;11g/dl in the first trimester and 10.5g/dl in the 2nd and third trimester [4]. Blood count and CHr was analyzed using Mindray fully automated analyzer BC 6800, Serum iron and TIBC was measured with Mindray BS 480 and Serum ferritin with Advia Centaur Xp. TS was calculated by dividing serum iron by TIBC and multiplying by 100. A data extraction sheet was used to enter the investigations with the results.&#x0D; Statistical Analysis: Data were double entered and were analyzed using Statistical Package for Social Sciences (SPSS) version 20. Descriptive statistical methods were used to calculate the median and the mean ± standard deviation of Hb, serum iron, serum ferritin, TIBC, TS, MCV, MCH, MCHC and CHr. Pearson’s correlation was used to evaluate the correlation between variables. Coefficient of determination (R Sq) was used to a statistical measure of how close the data are to the fitted regression line. P &lt; 0.05 was considered significant.&#x0D; Conclusion: Significant positive correlations were observed between the CHr and haematological parameters such as Hb, MCV, MCH, and MCHC and biochemical parameters including serum iron, serum ferritin, and TS (p value &lt; 0.001). Negative correlation was seen between the CHr and TIBC and there was no correlation with age. The mean value of CHr was 22.4 ±4.16pg and median was 22.2 pg.&#x0D;

Pure Red Cell Aplasia Related to Parvovirus B19 Infection in Simultaneous Pancreas and Kidney Recipient: A Case Report

A 42-year-old woman received a simultaneous pancreas and kidney transplantation (SPK). Immunosuppression consisted of tacrolimus modified release, prednisone, mycophenolate mofetil (MMF), and thymoglobulin as induction. The function of both grafts was good. Eight months after SPK, the patient suffered from weakness and arthralgia. Normocytic anemia with reticulocytopenia was revealed. In a bone marrow examination, giant pronormoblasts were found. Immunohistochemical staining of bone marrow and serum examination were positive for Parvovirus B19 (Parvo B19) confirming diagnosis of pure red cell aplasia (PRCA).The treatment consisted of MMF withdrawal, red-cell transfusions, immunoglobulins subcutaneously (SCIg) and immunosuppression reduction. Rapid improvement was observed with the rise of reticulocyte count and hemoglobin. Two months after the achievement of remission, the low dose of everolimus was added considering the high risk of rejection and antiviral potential of mTOR inhibitors. Three months later, PRCA relapsed. Retherapy with SCIg was still effective. Subsequent SCIg was supplemented due to low reticulocyte count and recurrent herpes zoster. The replication of Parvo B19 was persistent (serum qualitative test). Everolimus was withdrawn after 9 months of therapy due to the recurrence of PRCA and serious infections. The observation period after PRCA diagnosis lasts for 15 months. The patient is in good condition with no anemia and excellent grafts function. In conclusion, pure red cell aplasia related to Parvo B19 infection should be considered in transplant recipients with normocytic anemia and reticulocytopenia. The treatment with immunoglobulin G and immunosuppression reduction is an effective therapy. The role of everolimus in Parvo B19 infection requires future studies.

Reticulocyte count changes in paediatric patients with uncomplicated malaria treated with artemisinin combination therapy

Background: Acute malaria is associated with reticulocyte count depression, and artemisinin derivatives have also been shown to cause reversible count changesin patients with severe malaria. However, there has been no report on the effect of artemisinin on reticulocytecountwhen used in combination with other antimalarials, or the effect of artemisinin-based treatment on reticulocyte count changes in patients with uncomplicated malaria. Objective: This study reports the effects of artemisinin-based antimalarial treatments on reticulocytes among paediatric patients with uncomplicated malaria. Methods: The reticulocyte counts, haemoglobin, and platelet counts of children with uncomplicated malaria treated with artesunate-amodiaquine (116), artemether-lumefantrine (90), or amodiaquine (17) were measured before treatment (day 0) and then on days 3, 7, 14, and 28. Results: The fractional changes in reticulocyte counts were higher in the artesunate-amodiaquine and artemether-lumefantrine groups during the initial stages of treatment. However, the overall fractional reticulocyte change between acute illness and pre-illness levels was higher in the amodiaquine treated group. There was a negative correlation between haemoglobin and reticulocyte counts before treatment (day 0 ) and on all the follow up days. Conclusion: Treatment of uncomplicated malaria in children with artesunate-amodiaquine or artemether-lumefantrine was associated with less profound reticulocyte count changes compared with children treated with amodiaquine alone. These changes were most likely due to the rapid parasite clearance by the two artemisinin-based combination treatment regimens.

Reticulocyte count changes in paediatric patients with uncomplicated malaria treated with artemisinin combination therapy

Background: Acute malaria is associated with reticulocyte count depression, and artemisinin derivatives have also been shown to cause reversible count changes in patients with severe malaria. However, there has been no report on the effect of artemisinin on reticulocyte count when used in combination with other antimalarials, or the effect of artemisinin-based treatment on reticulocyte count changes in patients with uncomplicated malaria. Objective:This study reports the effects of artemisinin-based antimalarial treatments on reticulocytes among paediatric patients with uncomplicated malaria. Methods: The reticulocyte counts, haemoglobin, and platelet counts of children with uncomplicated malaria treated with artesunate-amodiaquine (116), artemether-lumefantrine (90), or amodiaquine (17) were measured before treatment (day 0) and then on days 3, 7, 14, and 28. Results: The fractional changes in reticulocyte counts were higher in the artesunate-amodiaquine and artemether-lumefantrine groups during the initial stages of treatment. However, the overall fractional reticulocyte change between acute illness and pre-illness levels was higher in the amodiaquine treated group. There was a negative correlation between haemoglobin and reticulocyte counts before treatment (day0) and on all the follow up days. Conclusion: Treatment of uncomplicated malaria in children with artesunate-amodiaquine or artemether-lumefantrine was associated with less profound reticulocyte count changes compared with children treated with amodiaquine alone. These changes were most likely due to the rapid parasite clearance by the two artemisinin-based combination treatment regimens

Gene Mutants and Their Clinical Characteristics of G6PD Deficiency Among Children in Luzhou Area

To study the gene mutants of G6PD deficiency and their clinical featuers among children in Luzhou area. 732 children with suspected G6PD deficiency in Luzhou area from March 2017 to July 2019 were selected, which were examined for G6PD enzyme activity and gene mutation. The G6PD enzyme activity was detected by ultraviolet rate quantification, and the gene mutation was detected by melting curve analysis-based PCR assay, and the clinical characteristics of different mutants when acute hemolysis happens were analyzed. 387 positive specimens were detected in 732 specimens, among which the gene mutation and the enzyme activity decrease was found in specimens 326, 49 specimens showed gene mutation but without the enzyme activity decrease, and 12 specimens without gene mutation but with the enzyme activity decrease. Among 375 positive samples with gene mutation, c.1376G＞T, c.1388G＞A, c.1024C＞T and c.95A＞G were the most common. The enzyme activity of c.1376G＞T and c.1388G＞A was statistically significantly different with c.1024C＞T. The most common incentives of acute hemolysis was broad bean, the reticulocyte count was statistically significantly different among c.1376G＞T, c.1388G＞A and c.95A＞G. The hemoglobin level of c.1376G＞T was statistically significantly different from with c.95A＞G. Moreover, c.1376G＞T, c.1388G＞A was lower than c.1024 C＞T. When acute hemolysis occurs, the reticulocyte count and hemoglobin changes were different between different mutation types, while the patients age, hospitalization time, blood transfusion, total bilirubin, and urine color recovery time of the patients were not statistically different. The common mutants of G6PD deficiency among children in Luzhou area are c.1376G＞T, and c.1388G＞A, c.1024C＞T. Favism is the most common clinical manifestation of G6PD deficiency.