Dose-response formation of N7-(3-benzo[1,3]dioxol-5-yl-2-hydroxypropyl)guanine in liver and urine correlates with micronucleated reticulocyte frequencies in mice administered safrole oxide.

Safrole oxide (SAFO), a metabolite of naturally occurring hepatocarcinogen safrole, is implicated in causing DNA adduct formation. Our previous study first detected the most abundant SAFO-induced DNA adduct, N7-(3-benzo[1,3] dioxol-5-yl-2-hydroxypropyl)guanine (N7γ-SAFO-G), in mouse urine using a well-developed isotope-dilution high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (ID-HPLC-ESI-MS/MS) method. This study further elucidated the genotoxic mode of action of SAFO in mice treated with SAFO 30, 60, 90, or 120 mg/kg for 28 days. The ID-HPLC-ESI-MS/MS method detected N7γ-SAFO-G with excellent sensitivity and specificity in mouse liver and urine of SAFO-treated mice. Our data provide the first direct evidence of SAFO-DNA adduct formation in rodent tissues. N7γ-SAFO-G levels in liver were significantly increased by SAFO 120 mg/kg compared with SAFO 30 mg/kg, suggesting rapid spontaneous or enzymatic depurination of N7γ-SAFO-G in tissue DNA. Urinary N7γ-SAFO-G exhibited a sublinear dose response. Moreover, the micronucleated peripheral reticulocyte frequencies increased dose-dependently and significantly correlated with N7γ-SAFO-G levels in liver (r = 0.8647; p < 0.0001) and urine (r = 0.846; p < 0.0001). Our study suggests that safrole-mediated genotoxicity may be caused partly by its metabolic activation to SAFO and that urinary N7γ-SAFO-G may serve as a chemically-specific cancer risk biomarker for safrole exposure.

Serum ferritin values in neonates <29 weeks' gestation are highly variable and do not correlate with reticulocyte hemoglobin content.

OBJECTIVES: To compare serum ferritin and RET-He values among extremely low gestational age neonates ELGANs with other markers of iron-deficient erythropoiesis. STUDY DESIGN: This is a secondary analysis of the NICHD Darbepoetin Trial. Study data from placebo recipients who had a serum ferritin, a RET-He, and a mean corpuscular volume (MCV) measurement within a 24-hour period were analyzed for correlation. RESULTS: Mixed linear regression models showed no association between ferritin and RET-He at both early (ß = 0.0016, p = 0.40) and late (ß = -0.0001, p = 0.96) time points. Positive associations were observed between RET-He and MCV at baseline, early, and late time points (p < 0.01, =0.01, <0.001, respectively), while ferritin was not associated with MCV at any time point. CONCLUSIONS: Our study shows that RET-He is better correlated with MCV as a marker of iron-limited erythropoiesis than ferritin. The results suggest that ferritin is limited as a marker of iron sufficiency in premature infants. STUDY IDENTIFICATION: FDA IND Number 100138; ClinicalTrials.gov number NCT03169881; NRN ID number NICHD-NRN-0058 (Darbe).

Screening of subclinical functional hemoglobin and red blood cell abnormalities among blood donors of Fayoum University Hospital in Egypt: Are RET-He, and IRF useful screening tools?

BACKGROUND: The effectiveness of red cell transfusion in a given blood unit that relied on both quantity and quality of donated cells undoubtedly affects prognostic outcomes. OBJECTIVE: We aimed to determine the frequency of subclinical functional hemoglobin and red cell abnormalities in donated blood of Fayoum University Hospital in Egypt. Additionally, to assess the usefulness of reticulocyte mean hemoglobin content (RET-He) and immature reticulocyte fraction (IRF) as screening measures for such abnormalities. MATERIAL AND METHODS: This cross-sectional study enrolled 200 volunteer blood donors who met the national standard criterion of blood donation. Complete blood count with reticulocyte parameters, serum ferritin, sickling test, G6PD assay, Mentzer index, and naked-eye single tube red cell osmotic fragility test were carried out. RESULTS: Functional red cell abnormalities represented 44 % of this cohort. Out of them, 4.5 % had iron deficiency, 11 % had a positive sickling test, 19 % had G6PD deficiency, and 9.5 % had suspicious thalassemia. The sensitivity and specificity test for RET-He in selective identification of functional hemoglobin abnormalities in donated blood were 83.3 % and 61.2 %, respectively at a cutoff value of 26.9. Though there was no statistically significant effect of RET-He on the selective detection of G6PD deficiency, IRF had a statistically significant high level with a p-value of 0.04. CONCLUSION: Subclinical functional red cell abnormalities seem to be prevalent among blood donors. Reticulocyte/ erythrocyte indices could be useful screening tools for red cell abnormalities. Further studies are required for assessing the impact of transfusing such abnormalities to neonates and other critical recipients.

Reference intervals for reticulocyte indices, immature reticulocyte fraction, and the percentage of hypochromic red blood cells in adult large breed dogs using the ADVIA 2120 hematology analyzer.

Reticulocyte indices are used to characterize anemia, including the identification of regeneration. In people, the immature reticulocyte fraction (IRF), percentage of hypochromic red blood cells (%HYPO-RBC), and other reticulocyte indices have been used as earlier indicators of erythropoiesis and as valuable monitoring tools in the assessment of various therapies. The reference intervals (RI) of the IRF and %HYPO-RBC have not been reported in dogs. The objective of this study was to establish RIs for novel variables (IRF, %HYPO-RBC, and CH-delta) and assess RIs for more commonly reported reticulocyte indices in healthy dogs. RIs were calculated from blood results retrospectively collected from 106 client-owned healthy dogs at the time of induction into a blood donor program using the ADVIA 2120 hematology analyzer (Siemens Healthcare Diagnostics). For the calculation of RIs, appropriate tests were applied for outlier detection and normality assessment. For variables normally distributed, RIs and their respective 90% confidence intervals (CIs) were calculated using parametric methods, while for variables not normally distributed, robust methods were used and bootstrapping for calculating the 90% CIs. The following RIs were established: reticulocyte hemoglobin content (CHr) 24.5-28 pg, mean reticulocyte volume (MCVr) 85.9-99.3 fL, mean corpuscular hemoglobin concentration of reticulocytes (CHCMr) 271.0-306.3 g/L, IRF 10.4%-43.5%, CH-delta 0.5-4.3 pg, and percentage of hypochromic red blood cells (%HYPO-RBC) 0.10%-0.80%. The results of this study provide RIs for novel reticulocyte variables. Further studies are required to determine the clinical utility of IRF, %HYPO-RBC, and CH delta as early indicators of erythropoietic activity in canine patients.

Importance of the reticulocyte hemoglobin equivalent in the exclusion of latent iron deficiency.

BACKGROUND: Iron deficiency is an underdiagnosed public health problem, especially in developing countries, that can conceal serious underlying illnesses. Early diagnosis and treatment of latent iron deficiency (LID) is crucial. Reticulocyte hemoglobin equivalent (RET-He), was reported to be a cost-effective tool that reflects the iron availability at erythropoiesis. The aims of this study were to evaluate the RET-He in the exclusion of LID. METHODS: Transversal study was carried out in the laboratory of clinical biology of Ben Arous regional hospital, it included volunteers in apparently good health. We performed a complete blood count and a serum ferritin assay. Participants with normal hemoglobin were divided into two groups: Control group G1: normal ferritin (≥ 15 ng/mL)/LID group G2: low ferritin (< 15 ng/mL). We compared the blood count parameters of the two groups. RESULTS: We selected 108 participants (G1: 88 (81.5%), G2: 20 (18.5%)), mean age = 36 years, gender-ratio = 0.92. We noted, in G2, significantly lower rates for hemoglobin Hb (p < 0.001), hematocrit (p < 0.001), mean corpuscular hemoglobin MCH (p = 0.026), reticulocyte count (p = 0.039) and RET-He (p < 0.001) and significantly higher rate for RDW/CV (p = 0.009). RET-He averages were 29.1 pg in G2 and 31.1pg in G1. In multivariate analysis, only RET-He showed a significant difference between the two groups. Area under the curve was 0.872, the cutoff = 30.9 (sensitivity 100%, specificity 61%, PPV 37%, NPV 100%). CONCLUSION: RET-He is an accessible and affordable parameter of the iron status, with an excellent NPV. It would be interesting to evaluate our results on a larger sample to define reference values in our population.

Bone marrow iron scoring in healthy and clinically ill dogs with and without evidence of iron-restricted erythropoiesis.

BACKGROUND: There are few reports in dogs that have evaluated the utility of semi-quantitative scoring of bone marrow iron stores in conjunction with reticulocyte hemoglobin (CHr) to identify iron-restricted erythropoiesis due to absolute iron deficiency or iron sequestration. OBJECTIVES: An established system for scoring iron stores in human bone marrow samples was applied to dogs. The objectives were to evaluate interobserver agreement (Κω ), determine marrow iron scores in dogs without detectable hematologic abnormalities, and assess combined interpretation of iron scores and CHr to evaluate for iron-restricted erythropoiesis. METHODS: Four blinded observers independently scored iron in 139 Prussian blue-stained canine marrow samples from 0 (none) to 6 (very heavy), including healthy controls (n = 12), clinically ill dogs with (n = 100) and without (n = 16) detectable hematologic abnormalities, and dogs with experimental nutritional iron deficiency (n = 11). Additional medical record data were available for 118 dogs to evaluate for other evidence of iron deficiency (abnormal CHr, RBC indices, serum iron variables, external blood loss, or nutritional deficiencies). RESULTS: Mean Κω was 0.69 (substantial agreement) for all samples but was 0.44 (moderate agreement) for samples with iron scores <3, indicating distinguishing scores 0-2 may not be reliable. Dogs without detectable hematologic abnormalities had scores from 3-5. Dogs with scores <3 and decreased CHr often had more indicators of iron deficiency vs dogs only having low iron scores or low CHr. CONCLUSIONS: Evaluation of dogs with marrow iron score <3 for external blood loss or nutritional deficiencies is likely clinically worthwhile, particularly if there is also decreased CHr.

Reticulocyte haemoglobin equivalent (RET-He) as an early marker of responsiveness to oral iron supplementation.

AIM: We investigated the potential of reticulocyte haemoglobin equivalent (RET-He) as an early marker of responsiveness to iron supplementation. METHODS: Data were obtained from a randomised controlled trial of daily iron supplementation in 356 Cambodian women (18-45 y) who received 60 mg elemental iron for 12 weeks. A fasted venous blood specimen was collected at baseline, 1-week and 12-week timepoints. Whole blood haemoglobin (g/L) and RET-He (pg) were measured using a Sysmex haematology analyser. RET-He measures were evaluated for their predictive ability on haemoglobin response to iron supplementation (defined as ≥10 g/L at 12 weeks). Receiver operating characteristic (ROC) curves were used to assess discrimination performance, and the area under the ROC curve (AUCROC) served as a measure of the ability of each predictor to discriminate between women likely or unlikely to elicit a haemoglobin response. RESULTS: Predictive ability (AUCROC (95% CI)) of baseline, 1-week, and change from baseline to 1-week RET-He on haemoglobin response was 0.70 (0.63 to 0.76), 0.48 (0.41 to 0.56) and 0.81 (0.75 to 0.87), respectively. Based on the Youden index, an absolute increase in RET-He of ~1.1 pg or a percentage increase of ~4.4% over 1 week were optimal thresholds to predict responsiveness to iron supplementation. CONCLUSION: Single timepoint RET-He measures have poor predictive ability; however, change in RET-He after 1 week was a strong predictor of haemoglobin response among Cambodian women receiving 60 mg elemental iron and can be measured easily and quickly after only 1 week of iron therapy.

The association of hepcidin, reticulocyte hemoglobin equivalent and anemia-related indicators on anemia in chronic kidney disease.

Hepcidin is an essential regulator of iron homeostasis in chronic kidney disease (CKD) anemia, reticulocyte hemoglobin equivalent (RET-He) can be used to evaluate the availability of iron for erythropoiesis. Previous research has found that hepcidin indirectly regulates RET-He. This study aimed to investigate the association of hepcidin, RET-He and anemia-related indicators on anemia in chronic kidney disease. A total of 230 individuals were recruited, including 40 CKD3-4 patients, 70 CKD5 patients without renal replacement therapy, 50 peritoneal dialysis patients, and 70 hemodialysis patients. The serum levels of hemoglobin (Hb), reticulocyte, RET-He, serum iron, serum creatinine, serum ferritin, total iron binding capacity, hepcidin-25, high sensitivity C-reactive protein, transferrin, erythropoietin, intrinsic factor antibody, soluble transferrin receptor and interleukins-6 (IL-6) were measured. Hepcidin-25 was positively associated with IL-6, and negatively with total iron binding capacity, intrinsic factor antibody, and transferrin. Reticulocyte Hb equivalent was associated positively with Hb, serum ferritin, serum iron, transferrin saturation, and negatively with serum creatinine, reticulocyte, IL-6, STfR. Hepcidin-25 was not associated with RET-He, while IL-6 was independently associated with hepcidin-25 and RET-He, suggesting that hepcidin has no effffect on the iron dynamics of reticulocytes in CKD, may be related to IL-6, indicate a likelihood of a threshold for stimulation of hepcidin-25 expression by IL-6 in order to indirectly regulates RET-He.

Reticulocyte Hemoglobin Equivalent has Comparable Predictive Accuracy as Conventional Serum Iron Indices for Predicting Iron Deficiency and Anemia in a Nonhuman Primate model of Infantile Iron Deficiency.

BACKGROUND: Infantile iron deficiency (ID) causes anemia and compromises neurodevelopment. Current screening relies on hemoglobin (Hgb) determination at 1 year of age, which lacks sensitivity and specificity for timely detection of infantile ID. Low reticulocyte Hgb equivalent (RET-He) indicates ID, but its predictive accuracy relative to conventional serum iron indices is unknown. OBJECTIVES: The objective was to compare diagnostic accuracies of iron indices, red blood cell (RBC) indices, and RET-He for predicting the risk of ID and IDA in a nonhuman primate model of infantile ID. METHODS: Serum iron, total iron binding capacity, unsaturated iron binding capacity, transferrin saturation (TSAT), Hgb, RET-He, and other RBC indices were determined at 2 wk and 2, 4, and 6 mo in breastfed male and female rhesus infants (N = 54). The diagnostic accuracies of RET-He, iron, and RBC indices for predicting the development of ID (TSAT < 20%) and IDA (Hgb < 10 g/dL + TSAT < 20%) were determined using t tests, area under the receiver operating characteristic curve (AUC) analysis, and multiple regression models. RESULTS: Twenty-three (42.6%) infants developed ID and 16 (29.6%) progressed to IDA. All 4 iron indices and RET-He, but not Hgb or RBC indices, predicted future risk of ID and IDA (P < 0.001). The predictive accuracy of RET-He (AUC = 0.78, SE = 0.07; P = 0.003) for IDA was comparable to that of the iron indices (AUC = 0.77-0.83, SE = 0.07; P ≤ 0.002). A RET-He threshold of 25.5 pg strongly correlated with TSAT < 20% and correctly predicted IDA in 10 of 16 infants (sensitivity: 62.5%) and falsely predicted possibility of IDA in only 4 of 38 unaffected infants (specificity: 89.5%). CONCLUSIONS: RET-He is a biomarker of impending ID/IDA in rhesus infants and can be used as a hematological parameter to screen for infantile ID.

Clinical utility of reticulocyte haemoglobin in the assessment of iron deficiency and iron deficiency anaemia in the paediatric population.

AIM: Reticulocyte haemoglobin (Ret-He) is a useful marker in the assessment of iron stores in adult and paediatric patients. It is currently not utilised in Pathology Queensland. The objective of this study is to verify Ret-He in our Pathology Queensland laboratory and assess the clinical utility in the assessment of iron deficiency (ID) and iron deficiency anaemia (IDA) in paediatric patients. METHODS: Samples from patients aged <18 years sent to the Pathology Queensland laboratory that had paired full blood count and iron studies were included in this study. A minimum of 120 samples were required for verification of testing requirements and a minimum of 30 samples per age range were required for confirmation of published age-related reference intervals. RESULTS: Published Ret-He reference intervals were confirmed for stated age ranges in normal (non-ID) patients. Ret-He below the reference range for age demonstrated a good correlation with ID and IDA. CONCLUSIONS: Ret-He is a useful marker in the assessment of ID and IDA in a paediatric population. It is not affected by acute or chronic inflammation. Ret-He is sensitive and specific (86% and 92%) for the diagnosis of ID.

Reticulocyte hemoglobin content changes after treatment of anemia of prematurity.

BACKGROUND: Iron deficiency during infancy is associated with poor neurological development, but iron overload causes severe complications. Appropriate iron supplementation is therefore vital. Reticulocyte hemoglobin content (RET-He) provides a real-time assessment of iron status and chracterezes hemoglobin synthesis in preterm infants. However, the existing literature lacks detailed reports assessing chronological changes in RET-He. The aim of this study was to assess the chronological changes in RET-He during oral iron dietary supplementation, and concomitant therapy with recombinant human erythropoietin (rHuEPO) in preterm very low birthweight infants. METHODS: Very low birthweight infants, admitted to our neonatal intensive care unit were analyzed retrospectively. Hemoglobin (Hb), reticulocyte percentage (Ret), mean corpuscular volume, RET-He, serum iron (Fe), and serum ferritin were recorded. Data at birth (T0), the initial day of rHuEPO therapy (T1), the initial day of oral iron supplementation (T2), 1-2 weeks (T3), 3-4 weeks (T4), 5-6 weeks (T5), and 7-8 weeks (T6) from the initial day of oral iron supplementation were extracted, and their changes over time were examined. RESULTS: Reticulocyte hemoglobin content was highest at birth and declined rapidly thereafter, especially after starting rHuEPO therapy. There was no upward trend in RET-He after the initiation of oral iron supplementation, with a slower increase during 5-6 weeks after the initiation of iron therapy. CONCLUSIONS: During the treatment of anemia of prematurity, low RET-He levels may be prolonged. Anemia of prematurity should therefore be assessed and treated on a case-by-case basis, while considering the iron metabolic capacity of preterm infants.

Identification of subclinical iron deficiency using new erythrocytes, leukocytes, and reticulocytes parameters during nonsevere acute infection in pediatric outpatients.

BACKGROUND: This study aims to investigate the diagnostic utility of new erythrocytes, leukocytes, and reticulocytes parameters for the identification of subclinical iron deficiency (ID) in children under 6 years with nonsevere acute infection in pediatric outpatients. METHODS: The study included 102 children with acute infections and 31 true ID. Traditional and new hematology parameters were measured in a Sysmex-XN®, along with C-reactive protein level, and iron parameters. Participants' ID were categorized as: the ferritin < 100 ng/mL, transferrin saturation < 20% was defined as "subclinical or functional ID (FID) in Group 1"; ferritin < 30 ng/mL, transferrin saturation < 20%, as "absolute-ID (AID)" in Group 2; ferritin < 12 ng/mL without anemia and infection, as "true ID" in Group 3. RESULTS: The frequencies of FID and AID among the 102 children with acute infection were 24% and 76%, respectively. Compared with the Group 2 patients, Group 1 had a significantly higher mean percentage of hypochromic erythrocytes (Hypo-He), and significantly lower levels of hemoglobin (Hb) and Hb content of reticulocytes (RET-He) (p < 0.05 for all). Compared with Group 2 and Group 3 patients, Group 1 had a significantly higher mean percentage of immature reticulocyte fraction (IRF) and immature granulocyte (IG) values (p < 0.05 for all). The RET-He, IRF%, Hypo-He%, and IG% cut-off values for predicting FID during infection were 27.0 pg, 10.6%, 2.5%, and 0.35% respectively. DISCUSSION: The RET-He, Hypo-He, IRF, and IG may be useful parameters for identifying subclinical ID in small children with nonsevere acute infection in pediatric outpatients.

Implementing Reticulocyte Hemoglobin Into Current Hematology Algorithms.

OBJECTIVES: This systematic review investigates reticulocyte hemoglobin's capabilities in screening iron deficiency and iron-deficiency anemia with and without comorbidities. METHODS: Participant background and laboratory characteristics were extracted from 14 unique studies between 2015 and 2022. Hemoglobin, reticulocyte hemoglobin, and mean cell volume (MCV) values were used in a meta-analysis for iron-deficiency anemia with no secondary conditions. Mean laboratory values for each patient population were calculated and then used to determine sensitivity, specificity, and the area under the curve (AUC) for iron deficiency and iron-deficiency anemia. The ferritin and reticulocyte hemoglobin ranges were calculated using the mean values. RESULTS: The meta-analysis demonstrates that hemoglobin and MCV values do not significantly differ between studies, unlike reticulocyte hemoglobin values. The reticulocyte hemoglobin range is smaller than ferritin for the controls, iron deficiency, and iron-deficiency anemia. Reticulocyte hemoglobin values less than 26 pg can distinguish iron-deficiency anemia, while 26 to 31.5 pg can distinguish iron deficiency, with an AUC of 0.889. The sensitivity and specificity are 92.3% and 100% for iron-deficiency anemia, 100% and 81.5% for iron deficiency, and 94.4% and 71.4% for both, respectively (reference range, <31.5 pg). CONCLUSIONS: Reticulocyte hemoglobin is potentially a quick screening test for iron deficiency and iron-deficiency anemia.

[Delta-He a new biomarker for a surgical clinic]. / Del'ta gemoglobina ­ novyi biomarker dlya khirurgicheskogo statsionara.

BACKGROUND: Delta-He the difference between hemoglobin content in reticulocytes and erytrocytes is a relatively new laboratory indicator that is easily measured in everyday practice. This parameter is directly related to iron bioavailability for hemoglobin synthesis and can reflect various conditions accompanied by cytokine expression including systemic inflammation. OBJECTIVE: To analyze the prospects for practical application of hemoglobin delta in assessment of neurosurgical patients throughout in-hospital treatment. MATERIAL AND METHODS: We analyzed complete blood counts (Sysmex XN-1000 analyzer) with optical determination of reticulocyte hemoglobin and automatic calculation of Delta-He in 82 neurosurgical patients. Exclusion criteria were severe decompensated comorbidities, exacerbation of chronic infectious processes, cancer of other organs. Blood sampling for analysis of delta-hemoglobin was carried out before all diagnostic and therapeutic measures. Reference interval is indicated by the analyzer manufacturer as 1.7-4.4 pg. RESULTS: Delta-He values at admission ranged from -1.8 to 6.1 pg. There was a consistent decrease of these values throughout 3-4 postoperative days. Then, the values could increase or continued to decrease. Increment of the index was noted in 76 patients (92.7%). Such dynamics was observed in case of uncomplicated postoperative period. Further decrease of Delta-He was observed in 6 patients (7.3%). These ones were characterized by a longer recovery after surgery, and the events required additional medical or surgical correction were recorded. Negative dynamics of Delta-He values could precede clinical manifestations of certain complication. Clarification of diagnosis and correction of therapy were accompanied by gradual increase of Delta-He values. CONCLUSION: Estimation of Delta-He values over time can be used for monitoring of patients and effectiveness of therapy. From a practical point of view, it is important that examination can be performed at any time of the day.

Role of Hemoglobin Content of Reticulocyte to Evaluate Anemia in Patients with Malignancy.

Anemia is common in patients with cancer and it's pathophysiology is complex and multifactorial . Conventional methods (Serum Iron, serum ferritin, TIBC, TSAT) to diagnosing iron deficiency anemia in cancer patients is affected by cancer type, duration, treatment, infection and inflammation related to cancer. RET-He measure the recent functional availability of iron and the correlation well with iron deficient / restricted erythropoiesis, and it is not affected by infection and inflammation related to cancer so it can be useful marker to rapidly rule out iron deficiency in cancer patients. Material: This is observation longitudinal study and study subjects including all type of diagnosed cancer patients with anemia (Hb <13 gm % in males and <12gm% in females) with or without treatment. Study duration was 18 month and 200 sample size was taken. Complete blood count (Hb, TLC, platelets, MCV, MCH, MCHC, reticulocyte hemoglobin) were analysed on SYSMEX XN 1000i. Serum Ferritin was estimated using AVANTOR CL-1000i and Serum iron, TIBC, TSAT was run on EBRA MANHEIN CHEM 5X machine. Bone marrow examination was done for diagnosis / staging . Iron stores were evaluated by Perl's Prussian blue stain and graded as per criteria laid down by Gale et al. Observation: At a cut off of 28.4 pg, RET-He achieved sensitivity of 96.77 % and specificity of 81.66% with NPV of 99.3% and PPV of 49.2% for iron deficient state in cancer patients. This cut off value rules out iron deficient erythropoiesis, reduces unnecessary iron studies and encourage early treatment of iron deficiency. There is also moderate agreement exist between iron stores of bone marrow and RET-He with Kappa 0.411 and p value <.0001. Conclusion: RET-He is better indicator of IDA in cancer patients as compared to other conventional methods of diagnosing IDA.This study also revealed a direct correlation between RET-He and bone marrow iron stores. In future it is advisable to use RET-He as a predictor of IDA, which is sensitive and specific at particular cut off points in routine evaluation in IDA in cancer patients.

Diagnostic value of reticulocyte indices for the assessment of the iron status of cats with chronic kidney disease.

BACKGROUND: Reticulocyte indices have been suggested as alternatives to transferrin saturation (TSAT) for iron status assessment in humans and dogs but they have not been evaluated thoroughly in cats. OBJECTIVES: To assess the value of the reticulocyte indices for the diagnosis of iron deficiency in cats with chronic kidney disease (CKD) and chronic hematuria associated with subcutaneous ureteral bypasses (SUBs). ANIMALS: Sixty-four cats: 16 healthy, 14 CKD without SUB, and 34 CKD with SUB. METHODS: Prospective observational cross-sectional study of cats presented for routine nephrology visits. Primary outcomes included assessment of the diagnostic values of erythrocyte indices (mean corpuscular volume, hemoglobin, and hemoglobin concentration: MCV, MCH, and MCHC) and reticulocyte indices (mean corpuscular volume, MCVr; corpuscular hemoglobin, CHr), using TSAT as reference. RESULTS: Iron deficiency was diagnosed in 9/64 cats (14%). A receiver-operating characteristic curve analysis yielded a moderate discriminatory value for CHr in this diagnosis: area under the curve [AUC] = .75 (95% confidence interval, 0.48-0.89); P = .006; sensitivity 67%, specificity 82% for a cutoff of 15.9 pg. This compared favorably to MCVr (AUC = .63; P = .29), MCV (AUC = .58; P = .45), MCH (AUC = .64; P = .19), and MCHC (AUC = .7; P = .03). CONCLUSION AND CLINICAL IMPORTANCE: CHr added moderate value to the diagnosis of iron deficiency in cats with CKD.

Reference intervals for reticulocyte parameters (reticulocyte haemoglobin equivalent and immature reticulocyte fraction) in first-trimester pregnancy.

Reticulocyte parameters including reticulocyte haemoglobin equivalent (Ret-He) and immature reticulocyte fraction (IRF) are newly recognised hematological parameters that are being used for diagnosis and follow-up of anaemic patients. Reference intervals of these parameters have been established in different populations, however, the data relating to pregnancy are still lacking. One hundred and fifty-five first-trimester pregnant females were screened and the reference interval was calculated after selecting the patient with fixed criteria. R statistical software was used for statistical calculations. We tried to establish a reference interval of Ret-He content and IRF in first-trimester pregnancy in our study.IMPACT STATEMENTWhat is already known on this subject? Ret-He and IRF have been established as the marker of iron deficiency and iron-deficiency anaemia in different age groups and as a marker of response to iron therapy. However, literature is scarce regarding the reference intervals of these parameters, especially in pregnancy.What do the results of this study add? This study establishes the reference interval of newer reticulocyte parameters in first-trimester pregnancy which is not yet established in the literature. Establishing a reference interval is required for any laboratory parameters to be used in the clinical context.What are the implications of these findings for clinical practice and further research? The results of this study may help in making a clinical decision regarding iron deficiency in early pregnancy which is one of the common clinical problems in pregnancy. This study also serves as a baseline study for further studies of reference intervals for newer reticulocyte parameters in pregnancy. A similar study with a larger study population and follow-up with iron therapy may establish these parameters as one of the important markers of iron deficiency in pregnancy and help institute iron therapy on case-to-case basis.

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.

Tracking immature reticulocyte proteins for improved detection of recombinant human erythropoietin (rhEPO) abuse.

Athletes abuse recombinant human erythropoietin (rhEPO) and erythropoiesis stimulating agents to increase hemoglobin mass and improve performance. To evade detection, athletes have developed sophisticated blood doping regimens, which often include rhEPO micro-dosing. Detection of these methods requires biomarkers with increased sensitivity and a sample matrix that is more amenable to frequent testing in the field. We have developed a method to measure two immature reticulocyte proteins, CD71 and ferrochelatase (FECH), and one total erythrocyte protein, Band 3, in dried blood spots (DBS). This method was tested in response to rhEPO administration after low doses, 40 IU/kg, micro-doses, 900 IU, or saline injection in 20 healthy subjects. During administration of low-dose rhEPO, the mean CD71/Band 3 and FECH/Band 3 ratio increased by 412 ± 197% and 250 ± 44%, respectively. The mean response for the current biomarker, RET%, increased by 195 ± 35%. During administration of rhEPO micro-doses, CD71/Band 3 increased to 127 ± 25% on day 35 and 139 ± 36% on day 39, while no increase was observed in RET%. After rhEPO administration, during the washout phase, mean values decreased to a minimum of 64 ± 4% and 64 ± 11% for CD71/Band 3 and RET%, respectively. However, CD71/Band 3 remained below 75% of baseline for at least 4 weeks after rhEPO injection, while RET% returned to baseline levels. The results demonstrate that immature reticulocyte proteins have a larger response to rhEPO administration than the current biomarker, RET%, and can be monitored in the DBS matrix.