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Context Endogenous and exogenous androgens increase circulating erythrocytes and hemoglobin but their effects on erythrocyte lifespan is not known. Objective To investigate androgen effects on immature and mature erythrocyte lifespan in humans and mice using novel nonradioactive minimally invasive methods. Design Human erythrocyte lifespan was estimated using alveolar carbon monoxide concentration and blood hemoglobin in Levitt's formula in hypogonadal or transgender men before and up to 18 weeks after commencing testosterone (T) treatment. Erythrocyte lifespan was estimated in androgen receptor knockout and wild-type mice after T or DHT treatment of intact females or orchidectomized males using in vivo biotin labelling of erythrocyte surface epitopes for reticulocytes (Ter119+CD71+) and 2 markers of erythrocytes (CD45–, Ter119+CD71–) monitoring their blood disappearance rate by flow cytometry. Results Before treatment, hypogonadal and transgender men had marked reduction in erythrocyte lifespan compared with controls. T treatment increased erythrocyte lifespan at 6 weeks but returned to pretreatment levels at 18 weeks, whereas serum T and blood hemoglobin were increased by T treatment remaining elevated at 18 weeks. In mice, T and DHT treatment had higher erythrocyte (but not reticulocyte) lifespan but neither orchidectomy nor androgen receptor inactivation significantly influenced erythrocyte or reticulocyte lifespan. Conclusion We conclude that hypogonadal men have reduced erythrocyte lifespan and acute androgen-induced increase in circulating erythrocyte lifespan may contribute to the well-known erythropoietic effects of androgens, but longer term effects require further investigation to determine how much they contribute to androgen-induced increases in circulating hemoglobin. [ABSTRACT FROM AUTHOR]

Background: During our years of working with ferrets in our laboratory animal facility, we observed that in several healthy young female ferrets, signs of anaemia could be detected during the entry examination although none of the ferrets expressed any clinical symptoms at the time of blood withdrawal. We aimed to compare the influence of inhalation anaesthesia with isoflurane and sevoflurane to restrained, awake ferrets on several blood parameters. After arrival at our facility all ferrets received a hormone chip to subdue oestrus. Routine blood withdrawal was conducted followed by routine blood work including haematology, clinical chemistry and electrolytes. Since the size of the cannula for implementation of the hormone chip is relatively large and the insertion probably quite painful the procedure was always performed during a short inhalation anaesthesia with isoflurane or sevoflurane. In ferrets showing anaemia (haemetocrit below 0.37 l/L, haemoglobin below 11 g/dL), we performed a control blood work (venous blood) the following week. In order to rule out an effect of inhalation anaesthesia on the laboratory results, the blood withdrawal was performed in restraint and awake ferrets without anaesthesia. The study was performed as randomized controlled crossover design. Results: Thirty ferrets were enrolled, and divided in three groups. Comparison of the three methods (isoflurane, sevoflurane or restraint and awake without anaesthesia) of blood withdrawal showed statistically significant (p < 0.05) differences in most haematological parameters (e.g. red blood cell count, haematocrit), clinical chemistry parameters (e.g. total protein, albumin, alkaline phosphatase) and electrolytes (e.g. sodium, chloride and potassium). Restraint ferrets without anaesthesia showed no signs of anaemia. In anaesthetized ferrets, reticulocytes were about four to six times lower compared to ferrets anaesthetized with isoflurane or sevoflurane. Conclusions: The results of the study suggest that inhalation anesthesia has a significant effect on hematological and biochemical parameters in ferrets. In particular, the detection of anemia in an animal undergoing inhalation anesthesia needs to be contextualized in a clinical setting and in research context. [ABSTRACT FROM AUTHOR]

Based on the relationship between the intracellular concentration of sickle hemoglobin S (HbS) and the delay that occurs prior to the onset of sickling following deoxygenation, targeting the intracellular HbS concentration is a recognized therapeutic approach for sickle cell disease (SCD). We and others have shown that restricting iron by dietary or pharmacologic means improves hematologic parameters, inflammation, and organ damage in mouse models of SCD. Clinical evidence corroborating these findings is confined to case reports and small case series studies, none of which account for treatment or α‐thalassemia. We hypothesize that increased transferrin saturation is associated with increased mean cellular hemoglobin concentration (MCHC) which in turn is associated with decreased red cell counts and worsening anemia. To investigate this hypothesis, we examined the relationships between transferrin saturation and MCHC with each of the parameters that define MCHC in sickle patients (HbSS without α‐thalassemia) and healthy volunteers (HVs). Results indicate that transferrin saturation and MCHC are positively correlated with each other in sickle patients and HV. In patients with SCD, MCHC and transferrin saturation are negatively correlated with RBC count and are not correlated with hemoglobin, whereas each is positively associated with HV. Transferrin saturation and MCHC are each positively correlated with the hemolysis marker, lactate dehydrogenase. These observations support a model where increased transferrin saturation contributes to higher intracellular HbS concentrations with subsequent increases in sickling and hemolysis in sickle patients, suggesting that pharmacologic approaches to decrease serum iron may provide a therapeutic approach for patients with SCD. Trial Registration: This study was registered with ClinicalTrials.gov identifiers: NCT00011648, NCT00081523, and NCT04817670. [ABSTRACT FROM AUTHOR]

Introduction: Reticulocyte count and novel derived parameters provide insight into the effectiveness of erythropoiesis and may be useful tools in the classification and diagnosis of anemias. However, there is no standardisation, so we consider it necessary that each laboratory evaluates the parameters according to its own methodology and instrumentation and establishes its own reference ranges. Our aim was to establish the reference intervals (RIs) of reticulocyte profile provided by the Beckman Coulter DxH 900 haematological autoanalyzer in our reference population. Methods: One hundred and seventy‐five healthy adults (18 to 62 years) were included. Subjects were collected from the blood donation centre of the Hospital Clínico San Carlos (Madrid, Spain) upon informed consent. Whole blood was collected and assayed for 14 haematological parameters on the Beckman Coulter DxH 900 analyzer in the haematology laboratory of the Clinical Analysis Department. RIs were established as per Clinical and Laboratory Standards Institute EP28‐A3c guidelines using three different statistical approaches. Results: RIs estimated using the non‐parametric method and the Harrell‐Davis bootstrap method were very similar. RIs estimated by the robust method were narrower. Gender partitioning was required for two haematological parameters (low haemoglobin density (LHD) and microcytic anaemia factor (MAF)). The rest of the parameters did not need to be partitioned according to Lahti's method. Conclusion: RIs have been established for 14 hematologic parameters of the reticulocyte profile for the Beckman Coulter DxH 900 haematology analyzer using a healthy cohort of adult subjects. [ABSTRACT FROM AUTHOR]

Plasmodium vivax is the most widespread of the different Plasmodium species able to infect humans and is responsible for most malaria cases outside Africa. An effective, strain-transcending vaccine that alleviates or suppresses erythrocyte invasion would be a game-changer in eliminating vivax malaria. Recently, the binding of P. vivax Reticulocyte Binding Protein 2b (PvRBP2b) to human Transferrin receptor (TfR1) has been described as essential for reticulocyte invasion, making this parasite protein an appealing vaccine candidate. Here, using P. vivax Cambodian clinical isolates in robust ex vivo invasion assays, we show that anti-PvRBP2b polyclonal and monoclonal antibodies that inhibit binding of PvRBP2b to TfR1 do not block P. vivax invasion into reticulocytes even at high concentrations. Anti-TfR1 antibodies do not inhibit P. vivax invasion either. Combinations at high concentrations of human monoclonal antibodies targeting different PvRBP2b epitopes do not inhibit invasion. Combinations of anti-PvRBP2b with anti-PvDBP do not enhance invasion inhibition caused by anti-PvDBP alone. We also show that the invasion of Cambodian P. vivax is trypsin-resistant while TfR1 is trypsin-sensitive, and we demonstrate that TfR1 is not recycled following trypsin treatment. We determined the PvRBP2b sequence of all isolates used in the invasion assays and analyzed polymorphism within epitopes recognized by anti-PvRBP2b antibodies. We show that polymorphism does not explain the absence of neutralization. Anti-PvRBP2b polyclonal antibodies recognized all four isolates tested in immunofluorescence assays while not inhibiting P. vivax invasion. Overall, our results demonstrate that PvRBP2b binding to TfR1 is not essential for invasion into reticulocytes of P. vivax Cambodian strains questioning the relevance of PvRBP2b as vaccine candidate. [ABSTRACT FROM AUTHOR]

BACKGROUND: Beneficial effects of breathing at FIO2 < 0.21 on disease outcomes have been reported in previous preclinical and clinical studies. However, the safety and intra-hospital feasibility of breathing hypoxic gas for 5 d have not been established. In this study, we examined the physiologic effects of breathing a gas mixture with FIO2 as low as 0.11 in 5 healthy volunteers. METHODS: All 5 subjects completed the study, spending 5 consecutive days in a hypoxic tent, where the ambient oxygen level was lowered in a stepwise manner over 5 d, from FIO2 of 0.16 on the first day to FIO2 of 0.11 on the fifth day of the study. All the subjects returned to an environment at room air on the sixth day. The subjects' SpO2, heart rate, and breathing frequency were continuously recorded, along with daily blood sampling, neurologic evaluations, transthoracic echocardiography, and mental status assessments. RESULTS: Breathing hypoxia concentration dependently caused profound physiologic changes, including decreased SpO2 and increased heart rate. At FIO2 of 0.14, the mean SpO2 was 92%; at FIO2 of 0.13, the mean SpO2 was 93%; at FIO2 of 0.12, the mean SpO2 was 88%; at FIO2 of 0.11, the mean SpO2 was 85%; and, finally, at an FIO2 of 0.21, the mean SpO2 was 98%. These changes were accompanied by increased erythropoietin levels and reticulocyte counts in blood. All 5 subjects concluded the study with no adverse events. No subjects exhibited signs of mental status changes or pulmonary hypertension. CONCLUSIONS: Results of the current physiologic study suggests that, within a hospital setting, delivering FIO2 as low as 0.11 is feasible and safe in healthy subjects, and provides the foundation for future studies in which therapeutic effects of hypoxia breathing are tested. [ABSTRACT FROM AUTHOR]

Abstract Background During our years of working with ferrets in our laboratory animal facility, we observed that in several healthy young female ferrets, signs of anaemia could be detected during the entry examination although none of the ferrets expressed any clinical symptoms at the time of blood withdrawal. We aimed to compare the influence of inhalation anaesthesia with isoflurane and sevoflurane to restrained, awake ferrets on several blood parameters. After arrival at our facility all ferrets received a hormone chip to subdue oestrus. Routine blood withdrawal was conducted followed by routine blood work including haematology, clinical chemistry and electrolytes. Since the size of the cannula for implementation of the hormone chip is relatively large and the insertion probably quite painful the procedure was always performed during a short inhalation anaesthesia with isoflurane or sevoflurane. In ferrets showing anaemia (haemetocrit below 0.37 l/L, haemoglobin below 11 g/dL), we performed a control blood work (venous blood) the following week. In order to rule out an effect of inhalation anaesthesia on the laboratory results, the blood withdrawal was performed in restraint and awake ferrets without anaesthesia. The study was performed as randomized controlled crossover design. Results Thirty ferrets were enrolled, and divided in three groups. Comparison of the three methods (isoflurane, sevoflurane or restraint and awake without anaesthesia) of blood withdrawal showed statistically significant (p

Background: Sickle cell disease is the most common genetic hemoglobinopathy globally and systemically affects body functioning, decreasing exercise capacity. Objective: To assess exercise capacity through the 6-minute walk test (6MWT) and biomarkers in children and adolescents with sickle cell disease. Materials and Methods: Cross-sectional study involving 20 children and adolescents from Brazil. Demographic and socioeconomic data were obtained. Baseline measurements included biomarkers (red blood cells, hemoglobin, hematocrit, white blood cells, platelets, reticulocytes, lactate dehydrogenase, creatine phosphokinase, C-reactive protein, interleukin 6, and fetal hemoglobin). The following data were obtained before, during, and after the 6MWT: heart rate, blood pressure, and peripheral oxygen saturation. Results: Eighteen children and adolescents ages 5–14 years old were analyzed, 61.1% boys, 100% black or brown, and 61.1% in primary education, with low household income. The average distance walked in 6MWT was 463.8 (137.7) m, significantly less than the predicted value (P <.001). The distance of 6MWT was associated positively with age (P =.042) and inversely with reticulocyte count (P =.42) and interleukin 6 (P =.00). Age modified the effect of interleukin 6 in younger children (P =.038). Conclusion: Our findings suggest increased baseline levels of biomarkers of hemolysis and inflammation impact on 6MWT performance. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Material and Methods Results Conclusions Hereditary spherocytosis (HS) is a congenital haemolytic disorder, resulting from plasma membrane protein deficiency of red blood cells (RBCs). Typical pathological signs are anemia, jaundice, and splenomegaly; in newborns, jaundice is the main symptom.This study focused on the state of art about the HS diagnosis, from traditional to innovative methods, including diagnostic algorithms that can be applied for pediatric and adult patients, for different laboratory diagnostic levels.The first erythrocyte parameters used for HS diagnosis were the mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), and red blood cell distribution width (RDW); nowadays new parameters are used in blood cell counter. Advia analyzers (Siemens Medical Solutions) supply the hyper‐dense cell percentage (% Hyper), which reflects the red blood cells hyperchromia. Sysmex instruments (i.e. XT‐4000i, XE‐5000, XN‐Series) provide the MicroR, that is the percentage of erythrocytes smaller than 60 fL, Hypo‐He, which is the percentage of erythrocytes with a content of hemoglobin less than 17 pg and % Hyper‐He, which represents the percentage of RBC with cellular hemoglobin content higher than 49 pg. CELL‐DYN Sapphire (Abbott Diagnostics) introduced the HPR parameter (% HPR), which represents the erythrocytes with hemoglobin > 410 g/L. Beckman Coulter instruments supply the mean sphered corpuscular volume (MSCV), which is the average volume of all erythrocytes, including mature erythrocytes and reticulocytes. Other reference tests for screening and diagnosis of HS are the acidified glycerol lysis test (AGLT), the eosin‐5‐maleimide (EMA) binding test and genetic testing by next‐generation sequencing.The diagnostic workup of hereditary spherocytosis could be improved thanks to all the available tests, including new molecular tools. However, it requires synergy between clinicians and laboratory staff, evaluating clinical manifestations, all available data related to the disease and the prognosis to fill the diagnostic gaps in the near future. [ABSTRACT FROM AUTHOR]

Objective: Hemoglobin A1c (HbA1c), a key indicator of glycemic status over the last 3 months, is increasingly favored by clinicians to diagnose diabetes. Iron deficiency anemia (IDA), the most prevalent anemia worldwide, may alter HbA1c levels. However, data from eastern India are scarce, and existing studies offer conflicting results. This study aimed to investigate the impact of IDA on HbA1c levels in nondiabetics and to explore the correlation of HbA1c with hemoglobin (Hb), parameters of the iron profile, and red blood cell (RBC) indices. Methods: This cross-sectional analytical study compared 60 euglycemic patients with IDA, aged 18 to 60, to 60 age- and sex-matched euglycemic individuals without anemia. Data analysis was performed using SPSS version 25, with significance set at P < .05. Spearman's rho correlation coefficients examined correlations between Hb, serum iron, serum ferritin, total iron binding capacity (TIBC), transferrin saturation, packed cell volume (PCV), reticulocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) with HbA1c. Multinomial logistic regression analyzed the relationships of HbA1c (dependent variable) with RBC indices and iron profile parameters (independent variables). Results: The mean (SD) HbA1c value for IDA patients was 6.5 (0.5)% compared to 5.13 (0.80)% for controls (P < .001). HbA1c showed significant negative correlations with Hb, PCV, serum iron, serum ferritin, transferrin saturation, MCV, MCH, and MCHC, while TIBC was positively correlated with HbA1c. Each unit decrease in Hb increased the likelihood of HbA1c values in the prediabetic and diabetic range by 2.61 times (95% CI = 1.65-3.50) and 2.40 times (95% CI = 1.81-3.77), respectively (P < 0.001). Conclusion: The study highlights a significant increase in HbA1c levels with the worsening of IDA in non-diabetics, indicating that IDA should be addressed before interpreting HbA1c results accurately. [ABSTRACT FROM AUTHOR]

We previously described a novel Plasmodium vivax invasion mechanism into human reticulocytes via the PvRBP2a-CD98 receptor-ligand pair. Using linear epitope mapping, we assessed the PvRBP2a epitopes involved in CD98 binding and recognized by antibodies from patients who were infected. We identified 2 epitope clusters mediating PvRBP2a-CD98 interaction. Cluster B (PvRBP2a431-448, TAALKEKGKLLANLYNKL) was the target of antibody responses in humans infected by P vivax. Peptides from each cluster were able to prevent live parasite invasion of human reticulocytes. These results provide new insights for development of a malaria blood-stage vaccine against P vivax. [ABSTRACT FROM AUTHOR]

Pancytopenia is an uncommon abnormality detected on a full blood count. Features of presentation tend to be non-specific, and are due to impaired functions of the cell lines involved. These can include fatigue, infection and bleeding. However, the aetiology of pancytopenia is extensive. This narrative review aims to provide a minimally invasive diagnostic algorithm for generalist clinicians to approach pancytopenia, including investigations into the underlying aetiology, and when a referral to the haematologist is warranted for further investigations such as bone marrow aspiration and trephine biopsy. [ABSTRACT FROM AUTHOR]

Therapeutic neutralization of Oncostatin M (OSM) causes mechanism‐driven anemia and thrombocytopenia, which narrows the therapeutic window complicating the selection of doses (and dosing intervals) that optimize efficacy and safety. We utilized clinical data from studies of an anti‐OSM monoclonal antibody (GSK2330811) in healthy volunteers (n = 49) and systemic sclerosis patients (n = 35), to quantitatively determine the link between OSM and alterations in red blood cell (RBC) and platelet production. Longitudinal changes in hematopoietic variables (including RBCs, reticulocytes, platelets, erythropoietin, and thrombopoietin) were linked in a physiology‐based model, to capture the long‐term effects and variability of therapeutic OSM neutralization on human hematopoiesis. Free serum OSM stimulated precursor cell production through sigmoidal relations, with higher maximum suppression (Imax) and OSM concentration for 50% suppression (IC50) for platelets (89.1% [95% confidence interval: 83.4–93.0], 6.03 pg/mL [4.41–8.26]) than RBCs (57.0% [49.7–64.0], 2.93 pg/mL [2.55–3.36]). Reduction in hemoglobin and platelets increased erythro‐ and thrombopoietin, respectively, prompting reticulocytosis and (partially) alleviating OSM‐restricted hematopoiesis. The physiology‐based model was substantiated by preclinical data and utilized in exploration of once‐weekly or every other week dosing regimens. Predictions revealed an (for the indication) unacceptable occurrence of grade 2 (67% [58–76], 29% [20–38]) and grade 3 (17% [10–25], 3% [0–7]) anemias, with limited thrombocytopenia. Individual extent of RBC precursor modulation was moderately correlated to skin mRNA gene expression changes. The physiological basis and consideration of interplay among hematopoietic variables makes the model generalizable to other drug and nondrug scenarios, with adaptations for patient populations, diseases, and therapeutics that modulate hematopoiesis or exhibit risk of anemia and/or thrombocytopenia. [ABSTRACT FROM AUTHOR]

Objective This study aimed to assess the iron status prior to discharge in very low birth weight (VLBW) infants utilizing reticulocyte hemoglobin content (CHr) and evaluate the impact of delayed cord clamping (DCC) on iron status. Study Design This is a retrospective analysis of VLBW infants from two tertiary level of care Neonatal Intensive Care Units. The primary outcome was the proportion of VLBW infants with low CHr (<29 pg) prior to discharge. Hematologic parameters were also compared between infants who received or did not receive DCC. Infants with a positive newborn screen for hemoglobin Bart's were excluded. Results Among the 315 infants included, 99 infants (31.4%) had low CHr prior to discharge. The median (interquartile range) CHr prior to discharge was 30.8 pg (28.4–39 pg). DCC was performed in 46.7% of infants. Hemoglobin at birth, discharge, and CHr prior to discharge were higher and the need for blood transfusion and the number of infants with low CHr prior to discharge were lower in the DCC group. Conclusion Approximately 31.4% of VLBW infants had low CHr near the time of discharge suggesting they were iron deficient. DCC improved hematological parameters prior to discharge in VLBW infants. CHr content can be used to guide iron supplementation in VLBW infants to potentially improve their iron status and long-term neurocognitive outcomes. Key Points DCC was associated with an improved hemoglobin and iron status at discharge in VLBW infants. CHr is an early and reliable marker for iron deficiency. Approximately one in three VLBW infants can be iron deficient at the time of discharge. [ABSTRACT FROM AUTHOR]

Purpose: The main aim of this study was to compare and analyze hematological profiles using menstrual blood, as an alternative to peripheral blood. Patients and Methods: This study used menstrual and peripheral blood samples from women who were menstruating. The design of this research is analytical observational. Results: Menstrual blood can show an overall hematological profile similar to peripheral blood. Data shows the detection of blood component parameters, white blood cells and reticulocytes in MB with a range within and outside normal blood. Data on MB that show higher values (WBC, MCH, MCHC, PLT, RDW-CV, PDW, MPV, P-LCR, PCT, neutrophils, lymphocytes, monocytes, basophils, reticulocytes, LFR, Ret-He) and lower values lower (RBC, HGB, HCT, MVC, RDW-SD, Eosinophils, IRF, MFR, HFR) when compared with peripheral blood controls. The hematological profiles of Menstrual and peripheral blood showed significant differences (p < 0.01) for several parameters, while several other parameters did not show significant differences (p > 0.05) according to the Wilcoxon test. Conclusion: All hematological profile parameters were detected in menstrual blood. The new concept that menstrual blood can be used as a supporting medium for hematological examinations opens up opportunities for developing independent hematological detection tools in productive women. [ABSTRACT FROM AUTHOR]

Introduction: Macrocytosis is common in various clinical settings and it is found in approximately 1.7-3.6% of people admitted for care for any cause. As we know macrocytic anemia are of two types MA and NMMA. Increased Reticulocyte maturation parameters seen in mostly MA and MDS. Aim: Clinicohaematological correlation of various reticulocyte maturation parameters in differential diagnosis of macrocytic anemia. Methods and materials: Prospective study was conducted over 100 samples. The samples were collected and run over 5 part hematology analyzer. Detailed history was obtained from the patients. Full and methodical clinical examination was done in all. Then we look for various RMF. Results: A total of 100 samples (cases -50, controls -50) were studied. In our study we took 50 blood samples of cases in which 05 MDS patients 13 patients with NMMA and 25 patients with MA while 07 DA patients. Out of 13 NMMA patients 09 males and 04 females, out of 05 MDS pt. 04 males and 01 females and in MA 15 males and 10 females. Conclusion: In conclusion it is crucial to differentiate between MA and NMMA. If the iron status, serum cobalamine and folate levels are normal and there is increased value of IRF and MRV the diagnosis of MDS should be considered. In this scenario the diagnosis of non megaloblastic macrocytic anemia is very rare. [ABSTRACT FROM AUTHOR]

Background: Chronic Kidney Disease (CKD) patients undergoing hemodialysis usually undergo anemia condition. Calculation of hemoglobin and other hematological parameters such as Ret-he (Reticulocyte Hemoglobin) and reticulocytes along with Glomerulus Filtration Rate (GFR) calculations determine the stage of CKD. Erythropoietin (EPO) administration is one of the important therapies for CKD patients. Initiation of EPO therapy, according to Kidney Disease Improving Global Outcome (KDIGO). Method: This study was an observational cross-sectional analytical study. This research was carried out from October 2023 to November 2023 at the Hemodialysis Installation of Dr. RSUD. R Sosodoro Djatikoesoemo Bojonegoro. Normality of the data using the Shapiro-Wilk test and differences in Ret-he levels, reticulocyte counts, and hemoglobin levels pre and post-administration of erythropoietin using paired t-test was used if the data were normally distributed and the Wilcoxon test if the data were not normally distributed. Results: This study results showed that there was an increase in ret-he levels pre and post-administration of erythropoietin with pre mean value of 30.50 ± 4.043 and post mean value was 32.20 ± 2.936. Reticulocyte levels also increase pre and post-administration of erythropoietin with a mean value of 1.63 ± 0.869 for pre-administration and 2.04 ± 0.915 for post-administration. Hemoglobin levels before giving erythropoietin with a value of 8.21 ± 0.855 and after giving erythropoietin the value was slightly increased to 8.29 ± 0.853. Ret-he and reticulocytes were significant differences between pre and post-EPO administration with p=0.000 and hemoglobin showed that there are no significant difference values pre and post-EPO with p=0.373. Conclusion: There is a significant difference (p-value 0.000) between Ret-He and Reticulocyte levels pre and post-erythropoietin treatment and there is no significant difference (p-value 0.373) Hemoglobin levels pre and post-erythropoietin treatment. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the methodological comparison of reticulocytes by using the intelligent learning system Faster R-CNN, a set of reticulocyte image detection systems developed using deep neural networks. Methods: We selected 59 EDTA-K2 anticoagulated whole blood samples and calculated the RET% using seven different Sysmex XN full-automatic hematology analyzers with Faster R-CNN in the laboratory. We compared and evaluated the methods and statistically analyzed the correlation between the various test results. Results: The results indicated a high degree of consistency between the seven Sysmex XN full-automatic hematology analyzers and Faster R-CNN in detecting RET%. The correlation coefficients were 0.987, 0.984, 0.986, 0.987, 0.987, 0.988, and 0.986, respectively. Conclusion: We found that the Sysmex XN full-automatic hematology analyzers in our laboratory using the Faster R-CNN system met the requirements of the methodological comparison of reticulocyte detection and this intelligent learning system can be a useful clinical tool. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate changes in erythrocyte morphology associated with alectinib and resulting hemolytic anemia. Methods: This was a retrospective analysis of patients with stage IV non-small-cell lung cancer (NSCLC) treated with alectinib. Erythrocyte morphology (by peripheral-blood film evaluation), hemogram, reticulocyte, direct Coombs tests, serum lactate dehydrogenase (LDH), haptoglobin, and indirect bilirubin levels were evaluated. Demographic characteristics of the patients were also collected. Results: In total, 13 patients (7 women) with a mean age of 52.0±10.5 years were included. Median pre-alectinib hemoglobin level was 12.1 g/ dL [minimum (min): 9.4, maximum (max): 16.2 g/dL]. In total, serum hemoglobin was decreased in 8 patients (61.5%) compared with pre-alectinib levels. The average serum hemoglobin level after alectinib use was determined as 11.6 g/dL (min: 8.5 g/dL, max: 13 g/dL). Serum hemoglobin was <10 g/dL in only 3 patients. De novo anemia developed in six patients. Peripheral blood examination revealed numerous microspheroacanthocytes, some echinocyte, rare fragmented erythrocytes, and generalized anisopoikilocytosis. Serum LDH levels were high in 6 of 13 patients (46.1%) receiving alectinib. Reticulocyte count was high in 10 of 13 patients (76.9%). A decrease in serum haptoglobin was observed in five patients (38.4%). Serum indirect bilirubin was high in two of the patients (15.3%). Conclusion: Alectinib caused changes in the erythrocyte membrane and non-immune hemolysis in almost all patients using it. Hemolytic anemia was not severe enough to require alectinib dose reduction or discontinuation. Physicians caring for patients receiving alectinib should be alert to hematological changes due to drug use. [ABSTRACT FROM AUTHOR]

Introduction: The pathophysiology of chronic subdural hematoma (CSDH) remains to be fully understood. Basic knowledge of the composition and features of cells in the CSDH fluid may contribute to the understanding of the seemingly complex processes involved in CSDH formation and recurrence. This study is the first to examine the composition of cells and of cellular features in both systemic blood and subdural fluid from CSDH patients. We hypothesized that the cellular composition and features in the hematoma fluid may be; 1) different from that in the systemic blood; 2) different between patients with and without recurrence; 3) and different between the first and second operation in patients with recurrent CSDH. Methods: Systemic blood and subdural hematoma fluid were collected from CSDH patients with and without recurrent CSDH at the time of primary and secondary surgery. Analyses of cells and cellular features included total number of white blood cells, erythroblasts, reticulocytes, platelets, neutrophilocytes, lymphocytes, monocytes, eosinophils, basophils, reticulocytes, immature granulocytes, mean corpuscular cell volume (MCV), mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, hemoglobin and hematocrit. Results: Of the 85 included patients, 20 patients were operated for a recurrent CSDH within 90 days follow-up. All cells found in the systemic blood were present in the CSDH fluid, but the composition was different (p < 0.0001). MCV was higher in the hematoma fluid from the primary operation of patients later developing a recurrent CSDH compared to patients not developing recurrence (p = 0.009). Also, the percentage distribution of inflammatory cells in hematoma fluid from patients with recurrent CSDH was different between the first and second operation (p = 0.0017). Conclusion: This study is the first to investigate the cellular composition of CSDH fluid. Compared to systemic blood and to a reference distribution, an increased number of immune cells were present in the hematoma fluid, supporting an inflammatory component of the CSDH pathophysiology. MCV was higher in the subdural fluid at time of the first operation of CSDH patients later developing recurrence. Clinical trial registration: The study was approved by the Scientific Ethical Committee of the Capital Region of Denmark (Journal no. H-20051073. [ABSTRACT FROM AUTHOR]

The article provides a comprehensive overview of pediatric hematologic disorders for acute care providers, covering diagnosis, stabilization, and management, with a focus on anemia, including its types, presentation, and laboratory evaluation, along with transfusion considerations and potential complications.

Introduction: Dapsone forms the backbone of multi-drug therapy (MDT) in leprosy and many other dermatological disorders. Haemolysis is its common side effect which often necessitates drug stoppage. Currently, wide variation in data of haemolysis with dapsone exists in literature ranging from 24.7% to 83% and none of the studies point towards the timing of onset of haemolysis/timing of maximal haemolysis which is important in therapeutic decision making regarding continuing or stopping the drug. This study aimed to answer such unanswered questions. Objectives: Primary: To estimate the fall in haemoglobin (Hb) levels after administering MDT for 3 months in patients with leprosy. Secondary: To determine factors associated with Hb change -- age, glucose-6-phosphate dehydrogenase (G6PD) status, pole of leprosy and duration of MDT taken (if any). Materials and Methods: All freshly diagnosed cases of Hansen's disease were studied for 3 months. At baseline, demographic data (age, sex), skin biopsy, slit skin smear and G6PD were taken. Haemoglobin (Hb), serum glutamate oxaloacetate transferase (SGOT), serum glutamate pyruvate transferase (SGPT), serum bilirubin, lactate dehydrogenase (LDH), reticulocyte count, peripheral blood smear (PBS) along with clinical photography was done at baseline, 1, 2 and 3 months. Results: Out of the 48 patients who completed the study: Mean Hb (g/dL) decreased from 13.37 at baseline to a minimum of 12.08 at 2 months, and then increased to 12.34 at 3 months. Of 42 patients (87.5%) with a fall in Hb, 13 (27.1%) had severe (fall >20%), 17 (35.4%) had moderate (fall 10--20%), 12 (25%) had mild fall (fall <10%) and in 6 (12.5%), there was no haemolysis. Reticulocyte count, LDH, SGOT and SGPT were significantly associated with haemolysis. Severe haemolysis occurred more frequently in the lepromatous spectrum. Conclusion: Dapsone causes maximal fall of hemoglobin by 1.29 g/dl at two months following which it increases. The fall of hemoglobin is reversible and hemoglobin starts to increase by 3 months of therapy making cessation of the drug unnecessary in most of the patients. [ABSTRACT FROM AUTHOR]

The parasite Plasmodium vivax preferentially invades human reticulocytes. Its merozoite surface protein 1 paralog (PvMSP1P), particularly the 19-kDa C-terminal region (PvMSP1P-19), has been shown to bind to reticulocytes, and this binding can be inhibited by antisera obtained by PvMSP1P-19 immunization. The molecular mechanism of interactions between PvMSP1P-19 and reticulocytes during P. vivax invasion, however, remains unclear. In this study, we analyzed the ability of MSP1P-19 to bind to different concentrations of reticulocytes and confirmed its reticulocyte preference. LC-MS analysis was used to identify two potential reticulocyte receptors, band3 and CD71, that interact with MSP1P-19. Both PvMSP1P-19 and its sister taxon Plasmodium cynomolgi MSP1P-19 were found to bind to the extracellular loop (loop 5) of band3, where the interaction of MSP1P-19 with band3 was chymotrypsin sensitive. Antibodies against band3- P5, CD71, and MSP1P-19 reduced the binding activity of PvMSP1P-19 and Plasmodium cynomolgi MSP1P-19 to reticulocytes, while MSP1P-19 proteins inhibited Plasmodium falciparum invasion in vitro in a concentration-dependent manner. To sum up, identification and characterization of the reticulocyte receptor is important for understanding the binding of reticulocytes by MSP1P-19. [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease (HbSS) is one of the main hemoglobinopathies that affect the indigenous tribes and is a significant cause of morbidity and mortality. The effectiveness and safety of alternative medicines for sickle cell disease patients require further scientific study. The proposed study was conducted to clinically evaluate the safety and effectiveness of T-AYU-HM Premium Tablet (300 mg). Materials and Methods: This is a single-arm observational retrospective cohort study of 100 sickle cell disease subjects. Based on inclusion and exclusion criteria, the clinical and vital information of the patients was acquired, assessed, and reported. A follow-up period of 120±10 days was deemed sufficient. Data were analysed using a statistical package for the social sciences (SPSS). Results: The levels of haemoglobin (g/dL) (9.43±1.83 to 10.11±1.37) and red blood cells (/mm3) (3.89±0.81 to 4.18±0.64) were significantly improved (p<0.05). Reticulocyte count (%) changed significantly from 4.51±3.20 to 2.84±2.34. The number of blood transfusions (7.12±26.80 to 00) and the percentage of hospitalisations (76% to 00) that occurred more than six times prior to presentation were significantly reduced. Conclusion: In this retrospective analysis, there were no reported adverse consequences. Patient's responses and all the clinical parameters like haematology, liver function parameters, clinical, and pain-associated symptoms with the disorder showed T-AYU-HM Premium to be an effective and safer therapy in the treatment of sickle cell anemia. Further well-planned interventional studies may become useful to justify the same. [ABSTRACT FROM AUTHOR]

Introduction: The International Council for Standardization in Haematology convened a working group to assess and propose improvements upon the state of standardization and harmonization of reticulocyte parameters among commercial hematology analyzers. Methods: An international group of laboratory hematologists prospectively collected and analyzed clinical samples using locally available IVD commercial hematology analyzers. Eight hundred and fifty‐five total samples were collected at 6 sites using 9 distinct analyzer types. Samples were assessed for reticulocyte percent (RET%), immature reticulocyte fraction (IRF), and reticulocyte hemoglobin content (RHC). Method comparison and regression statistics were calculated. These analyses were used to determine whether statistical recalibration offered a potential avenue for increasing comparability between these methods. Results: While methods producing reticulocyte percent were the most comparable in this study, the state of harmonization for the IRF and RHC was reduced with pearson correlation coefficients ranging from 0.955 to 0.77 and 0.927 and 0.680, respectively. Nevertheless, use of parameters from the Passing Bablok regression substantially improved the comparability of the results. In addition, precision data was derived which also demonstrated substantial differences between analyzer systems. Conclusion: While reticulocyte counting is correlated between the automated methods evaluated in this study, the current state of harmonization of other reticulocyte parameters is not as strong. A major challenge in moving this field forward is the need for commutable materials to facilitate comparisons between analyzers not co‐located. A potential alternate approach to improve the current state would be instrument re‐calibration. However, this is challenging both technically and due to national regulatory frameworks. [ABSTRACT FROM AUTHOR]

Background: Reticulocytes are red blood cell precursors with an average lifespan of 1-2 days. Reticulocyte hemoglobin equivalent (Ret-He) is an early marker of iron deficiency (ID) erythropoiesis and reflects real-time information regarding the synthesis of young erythrocytes in the bone marrow. The objective of this study is to determine the diagnostic utility of Ret-He in patients having microcytic hypochromic anemia in comparison with serum ferritin and iron studies. Objectives: The objective of this study is to determine the diagnostic utility of the Ret-He parameter in patients having microcytic hypochromic anemia in comparison with the serum ferritin, iron studies and its role in routine hematological screening for nutritional deficiency anemia like ID. Design and Settings: The design involves observational study. Materials and Methods: A hospital-based observational study was carried out in a referral hospital. Hematological parameters were processed using Sysmex XN1000 (Sysmex Corporation, Kobe, Japan) analyzer and were compared with Serum iron studies using biochemistry analyzer (VITROS® 250 Chemistry System) from 201 participants who presented with microcytic hypochromic anemia. Main Outcome and Measures: Relationship of Ret-He parameter and its diagnostic utility for screening of iron-deficient states. Sample Size: The sample size was 201. Results: When serum ferritin is taken as "the gold standard" to detect ID, with Ret-He cutoff of 27.15 pg/cell, we found a statistically significant positive correlation between Ret-He and serum ferritin (P < 0.001). We found a sensitivity of 57.37% and specificity of 75.95% with area under the curve of 0.681, positive predictive value of 100%, negative predictive value of 3.8%, and accuracy of 62.19% for Ret-He in detecting ID anemia (IDA). Also found a statistically significant negative correlation between Ret-He and total iron binding capacity (P < 0.001). There was no statistical correlation between Ret-He and serum iron levels in our study. Conclusions: The present study suggests Ret-He is one of the better and more reliable hematological parameters indicating ID and, when used along with biochemical parameters like serum ferritin, can give valuable inputs in a better screening and diagnosis of IDA; hence proper treatment is possible. Limitations: The multicentric study is required to standardize Ret-He reference values, and follow-up to therapy of the subjects was not done. Additional hemoglobin variant analysis data would have been favorable to the study. [ABSTRACT FROM AUTHOR]

Aims and objectives: To analyze anti-MMP mode of action of Quaternary Ammonium Silane (QAS, codenamed as k21) by binding onto specific MMP site using computational molecular simulation and Anti-Sortase A (SrtA) mode of action by binding onto specific site using computational molecular simulation. Materials and methods: In silico Molecular Dynamics (MD) was used to determine the interactions of K21 inside the pocket of the targeted protein (crystal structure of fibroblast collagenase-1 complexed to a diphenyl-ether sulphone based hydroxamic acid; PDB ID: 966C; Crystal structure of MMP-2 active site mutant in complex with APP-derived decapeptide inhibitor. MD simulations were accomplished with the Desmond package in Schrödinger Drug Discovery Suite. Blood samples (~ 0.5 mL) collected into K2EDTA were immediately transferred for further processing using the Litron MicroFlow® PLUS micronucleus analysis kit for mouse blood according to the manufacturer's instructions. Bacterial Reverse Mutation Test of K21 Molecule was performed to evaluate K21 and any possible metabolites for their potential to induce point mutations in amino acid-requiring strains of Escherichia coli (E. coli) (WP2 uvrA (tryptophan-deficient)). Results: Molecular Simulation depicted that K21 has a specific pocket binding on various MMPs and SrtA surfaces producing a classical clouting effect. K21 did not induce micronuclei, which are the result of chromosomal damage or damage to the mitotic apparatus, in the peripheral blood reticulocytes of male and female CD-1 mice when administered by oral gavage up to the maximum recommended dose of 2000 mg/kg. The test item, K21, was not mutagenic to Salmonella typhimurium (S. typhimurium) strains TA98, TA100, TA1535 and TA1537 and E. coli strain WP2 uvrA in the absence and presence of metabolic activation when tested up to the limit of cytotoxicity or solubility under the conditions of the test. Conclusion: K21 could serve as a potent protease inhibitor maintaining the physical and biochemical properties of dental structures. [ABSTRACT FROM AUTHOR]

Introduction: Detection of iron deficiency (ID) remains challenging. We aimed to evaluate the performance of reticulocyte hemoglobin equivalent (Ret‐He) as a potential diagnostic marker to assess ID and iron deficiency anemia (IDA) in a large pediatric cohort. Methods: A total of 3158 patients (aged 15 days to 19 years with a median age of 8.5 years; 60.2% female) were retrospectively studied. Statistical analysis was performed (a) to evaluate relationship of Ret‐He with other relevant complete blood count and iron panel parameters; (b) to compare the levels of Ret‐He in ID and IDA groups to a control group; and (c) to assess sensitivity and specificity of Ret‐He in ID, IDA, and anemia without ID groups. Results: Ret‐He values were significantly positively correlated to ferritin and transferrin saturation (TSAT). The median Ret‐He was significantly lower in ID. A Ret‐He cutoff of ≤30.0 pg distinguished cases of ID from the control group with a sensitivity of 90.2%, specificity of 59.5%, and area under curve (AUC) of 0.88. Ret‐He showed better diagnostic performance in the IDA group and acceptable performance for ID without anemia. The sensitivity, specificity, and AUC were 90.1%, 80.9%, and 0.93 for IDA at cutoff value of ≤27.4 pg, and 80.8%, 51.1%, and 0.70 for ID without anemia at cutoff value of ≤30.8 pg, respectively. Conclusion: Our large pediatric tertiary care hospital study demonstrates that Ret‐He is a reliable marker to help confirm IDA in pediatric population. However, further studies are needed for its use to capture the early stages of ID. [ABSTRACT FROM AUTHOR]

Introduction: The Atellica Hema (Siemens Healthineers, Tarrytown, NY, USA) is a new generation multi‐parameter analyzer for full blood count, 6‐part differential and reticulocyte testing by impedance variation and fluorescence flow cytometry. In this study, we verified the whole blood and limited body fluid modes of the Atellica Hema 580. Methods: We evaluated precision, linearity, carry‐over, throughput and performed a method comparison to assess the performance of the Atellica Hema 580. For comparison of the Atellica Hema 580 with the Sysmex XN‐1000 (Sysmex, Kobe, Japan), 140 samples from adult and pediatric patients including both normal and abnormal hematology profiles were analyzed in parallel. Results: The Atellica Hema 580 demonstrated acceptable imprecision within the manufacturer's specifications for whole blood and body fluid modes, good linearity for high and low ranges and no significant carryover. The full blood count, differential and reticulocyte correlated well with the Sysmex XN‐1000, except for mean cell hemoglobin concentration, basophil and large immature cells. The optical platelet count, reflexed in 34 samples with a platelet count <150 × 109/l, showed a strong correlation with the fluorescent platelet count on the Sysmex XN‐1000. The morphology flagging efficiency was 92% for white blood cells, 95% for red blood cells and 87% for platelets. Conclusion: The Atellica Hema 580 showed good analytical performance and workflow efficiency for a wide range of patient samples. [ABSTRACT FROM AUTHOR]

The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood. Here, we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore, we utilize automated patch clamp, based on planar chips, to compare the activity of the two channels in reticulocytes and mature RBCs. In addition to this characterization, we performed membrane potential measurements to demonstrate the effect of channel activity and interplay on the RBC properties. Both the Gárdos channel and Piezo1, albeit their average copy number of activatable channels per cell is in the single-digit range, can be detected through transcriptome analysis of reticulocytes. Proteomics analysis of reticulocytes and mature RBCs could only detect Piezo1 but not the Gárdos channel. Furthermore, they can be reliably measured in the whole-cell configuration of the patch clamp method. While for the Gárdos channel, the activity in terms of ion currents is higher in reticulocytes compared to mature RBCs, for Piezo1, the tendency is the opposite. While the interplay between Piezo1 and Gárdos channel cannot be followed using the patch clamp measurements, it could be proved based on membrane potential measurements in populations of intact RBCs. We discuss the Gárdos channel and Piezo1 abundance, interdependencies and interactions in the context of their proposed physiological and pathophysiological functions, which are the passing of small constrictions, e.g., in the spleen, and their active participation in blood clot formation and thrombosis. [ABSTRACT FROM AUTHOR]

Objective To explore critical regulatory genes in the hemoglobin switch process by analyzing transcriptomic data from the GSE6236, GSE17639 and GSE35102 datasets. Methods The mRNA expression profiles of the three datasets were downloaded from the GEO database and gene annotation was performed using the AnnoProbe package.The remove-BatchEffect function of the Limma package was used to remove batch effects. Weighted gene co-expression network analysis (WGCNA) was used to explore the most relevant modular genes in reticulocytes. The receiver operating characteristic curve (ROC) was used to assess the value of differential genes in differentiating between cord blood and adult peripheral blood reticulocytes. The GSE35102 dataset was used to validate changes in differential gene expression during hemoglobin transformation. Finally, real-time quantitative PCR was used to verify differential gene expression in cord blood and adult peripheral blood reticulocytes. Results Twelve genes showed differential expression in reticulocytes from cord blood and adult peripheral blood ( |logFC|≥1.5, P

Abstract Background Knowledge of the diversity of invasion ligands in malaria parasites in endemic regions is essential to understand how natural selection influences genetic diversity of these ligands and their feasibility as possible targets for future vaccine development. In this study the diversity of four genes for merozoite invasion ligands was studied in Ecuadorian isolates of Plasmodium vivax. Methods Eighty-eight samples from P. vivax infected individuals from the Coast and Amazon region of Ecuador were obtained between 2012 and 2015. The merozoite invasion genes pvmsp-1-19, pvdbpII, pvrbp1a-2 and pvama1 were amplified, sequenced, and compared to the Sal-1 strain. Polymorphisms were mapped and genetic relationships between haplotypes were determined. Results Only one nonsynonymous polymorphism was detected in pvmsp-1-19, while 44 nonsynonymous polymorphisms were detected in pvdbpII, 56 in pvrbp1a-2 and 33 in pvama1. While haplotypes appeared to be more related within each area of study and there was less relationship between parasites of the coastal and Amazon regions of the country, diversification processes were observed in the two Amazon regions. The highest haplotypic diversity for most genes occurred in the East Amazon of the country. The high diversity observed in Ecuadorian samples is closer to Brazilian and Venezuelan isolates, but lower than reported in other endemic regions. In addition, departure from neutrality was observed in Ecuadorian pvama1. Polymorphisms for pvdbpII and pvama1 were associated to B-cell epitopes. Conclusions pvdbpII and pvama1 genetic diversity found in Ecuadorian P. vivax was very similar to that encountered in other malaria endemic countries with varying transmission levels and segregated by geographic region. The highest diversity of P. vivax invasion genes in Ecuador was found in the Amazonian region. Although selection appeared to have small effect on pvdbpII and pvrbp1a-2, pvama1 was influenced by significant balancing selection.

Simple Summary: Anemia is a frequent problem in small animals with several underlying causes, each one with different treatments and prognosis. When facing a sick patient, veterinary clinicians need to correctly identify the problem behind this pathology as soon as possible. Some hematology analyzers provide a new parameter (the immature reticulocyte fraction, IRF) which has been used in human medicine for this purpose. Our results show that IRF is also able to differentiate between some causes of anemia. This new parameter may help veterinary clinicians to further advance in their diagnosis and focus on more specific tests for their patients. The Sysmex XN-1000V analyzer can identify those reticulocytes with high RNA content and fluorescence, providing the immature reticulocyte fraction (IRF). While this parameter has been used in human medicine to identify the cause of anemia, few studies have focused on its use in veterinary medicine. In this study, we determined the IRF and related reticulocyte parameters in a large population of non-anemic and anemic dogs and cats (subclassified depending on the origin of their anemia). The IRF was significantly higher in hemolytic anemias compared to hemorrhagic ones in both species. Moreover, the IRF was significantly lower in dogs and cats with bone marrow failure than in other non-regenerative anemias and in both groups compared to pre-regenerative anemias. The accurate cut-off values for the differential in regenerative anemias and reference ranges for both species using the Sysmex XN-1000V are also reported. The measurement of the IRF in this analyzer can help clinicians to further classify the type of anemia in both species. [ABSTRACT FROM AUTHOR]

Blood doping is prohibited for athletes but has been a well‐described practice within endurance sports throughout the years. With improved direct and indirect detection methods, the practice has allegedly moved towards micro‐dosing, that is, reducing the blood doping regime amplitude. This narrative review evaluates whether blood doping, specifically recombinant human erythropoietin (rhEpo) treatment and blood transfusions are performance‐enhancing, the responsible mechanism as well as detection possibilities with a special emphasis on micro‐dosing. In general, studies evaluating micro‐doses of blood doping are limited. However, in randomized, double‐blinded, placebo‐controlled trials, three studies find that infusing as little as 130 ml red blood cells or injecting 9 IU × kg bw−1 rhEpo three times per week for 4 weeks improve endurance performance ~4%–6%. The responsible mechanism for a performance‐enhancing effect following rhEpo or blood transfusions appear to be increased O2‐carrying capacity, which is accompanied by an increased muscular O2 extraction and likely increased blood flow to the working muscles, enabling the ability to sustain a higher exercise intensity for a given period. Blood doping in micro‐doses challenges indirect detection by the Athlete Biological Passport, albeit it can identify ~20%–60% of the individuals depending on the sample timing. However, novel biomarkers are emerging, and some may provide additive value for detection of micro blood doping such as the immature reticulocytes or the iron regulatory hormones hepcidin and erythroferrone. Future studies should attempt to validate these biomarkers for implementation in real‐world anti‐doping efforts and continue the biomarker discovery. [ABSTRACT FROM AUTHOR]

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Iron-deficiency anemia (IDA) is a global health concern, and its widespread prevalence and multifaceted impact on various populations, particularly in developing countries, underscore the urgency for efficient diagnostic and management strategies. While traditional diagnostic methods such as ferritin and transferrin saturation are fundamental, their limitations in sensitivity and specificity lead to challenges in the early detection and effective management of IDA. This review provides a comprehensive analysis of IDA, focusing on the evolution of diagnostic methods culminating in the utilization of reticulocyte hemoglobin content (CHr) as a critical biomarker. The core of this review is the detailed examination of CHr as a biomarker. Its emergence has been pivotal due to its superior sensitivity and specificity in identifying iron deficiency and monitoring therapy efficacy. The review discusses the comparative advantages of CHr over conventional methods, including its ability to detect IDA at an earlier stage and its utility in varied demographic groups, such as children and pregnant women. Future research directions are proposed, including integration of CHr into routine clinical practice, cost-effectiveness analysis, and technological advancements for enhanced measurement and accessibility. In conclusion, CHr holds significant potential for revolutionizing IDA management, paving the way for more precise and personalized medical interventions, thereby improving patient outcomes in diverse populations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Avascular necrosis (AVN) is regarded as a manifestation of severe sickle cell disease (SCD), with the femoral head being the most affected. OBJECTIVES: The main objectives of this study were to look for the frequency of AVN in pediatric patients with SCD, evaluate the clinical pattern and severity of AVN, and study the possible risk factors associated with AVN. MATERIALS AND METHODS: A cross-sectional study has been conducted on SCD patients, aged 6-18 years, who visited the Basrah Center for Hereditary Blood Diseases from the first of February 2021 to August 2021. Patients were screened for AVN by hip plain radiography and magnetic resonance imaging. The modified Ficat-Arlet staging system was used to classify different stages of AVN. RESULTS: The total number of screened patients was 291; 193 (66.3%) had sickle cell anemia, 71 (24.4%) with S/β0 thalassemia, 21 (7.2%) with S/β+ thalassemia, and 6 (2.1%) had S/D disease. Fifty-eight (19.9%) patients were found to have different stages of AVN; 7 (12.1%) were asymptomatic and 51 (87.9%) were symptomatic. The logistic regression analysis has revealed that frequent vaso-occlusive crises requiring hospitalization (B = 1.576, P = 0.003), acute splenic sequestration crises (B = 1.256, P = 0.003), homozygous sickle hemoglobin genotype (B =-0.208, P = 0.001), and low reticulocyte count (B = 1.452, P = 0.027) are significant variables associated with AVN. CONCLUSION: AVN was reported in a significant percentage of pediatric patients with SCD and was associated with selected indicators of disease severity. Further studies that evaluate the natural history, progress of AVN, and variations in selected variables over time like reticulocytes and the co-inheritance of α-thalassemia are important. [ABSTRACT FROM AUTHOR]

Introduction: Chronic lymphocytic leukemia (CLL) has long been known for its complications related to immune deregulation, of which autoimmune cytopenias (AIC) were frequently reported. Ibrutinib has dramatically changed the overall prognosis of patients with CLL. However, whether ibrutinib can induce or aggravate AIC in CLL patients is still disputable. Here we report a CLL patient with pure red cell aplasia (PRCA) occurring during ibrutinib treatment and review available data to discuss the possible role of ibrutinib in developing AIC. Case report: A 70-year-old female was diagnosed with CLL with indications to initiate ibrutinib treatment given progressive bulky disease. She was admitted for advanced fatigue on the 14th day of ibrutinib monotherapy. A complete blood count revealed severe anemia of hemoglobin (Hb) 37 g/L and a meager reticulocyte count. After excluding other conditions that could cause anemia, PRCA was diagnosed as a complication of CLL. Management and outcome: Ibrutinib was discontinued on the day of admission. At the same time, the patient received prednisone and intravenous immunoglobulin (IVIg). Five days later, the Hb did not improve. Cyclosporine A (CsA) was added; IVIg was discontinued, and prednisone was tapered. Ten days later, the Hb had risen to 92 g/L with a high reticulocyte count of 0.279 × 1012/L. The CLL treatment restarted with Zanbrutinib in combination with a low dose of prednisone and CsA. Her CLL was in partial remission by the latest follow-up with an average Hb count. Discussion: Our case demonstrates a need to evaluate the risk of developing AIC before initiating ibrutinib. For patients with high-risk factors for AIC episodes, the transient addition of other immunosuppressive therapies should be taken into consideration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The 'Thomas plot' is a very helpful diagnostic tool for evaluation, monitoring and therapy of the iron status and on the hemoglobinization of the reticulocytes of patients. In 2021 Roche Diagnostics launched a second generation assay for determination of the soluble transferrin receptor (sTfR). Here we compare the old and the new assay for sTfR and analyze the consequences for the 'Thomas plot'. Measurement of sTfR, ferritin and CRP were done using a Cobas8000 system. Hemoglobin content of reticulocytes (Ret-He) was determined using a Sysmex XN9000 system. The second generation of sTfR assay showed consistently lower sTfR values compared to the first generation, which would result in a left shift of the 'Thomas plot' and may lead to false diagnosis of patients using the original cut-offs. Fifteen thousand five hundred ninty two data sets for 'Thomas plot' from 2016 to 2021 were retrospectively analyzed to estimate how many patients in our hospital would be affected. In result around 5 % of all 'Thomas plots' would be affected by the lower sTfR values of the second generation assays. Due to the lower sTfR values measured with the second generation assay new cut-offs for the Ferritin-Index (sTfR/lg Ferritin) should be used in order to correctly diagnose the iron status of patients. [ABSTRACT FROM AUTHOR]