Immature Reticulocyte Fraction Research Articles

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

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

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

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

Biochemical Changes in Adult Male Gamers During Prolonged Gaming: Pilot Study.

Gaming has become an integrated part of life for children and adults worldwide. Previous studies on the impact of gaming on biochemical parameters have primarily addressed the acute effects of gaming. The literature is limited, and the study designs are very diverse. The parameters that have been investigated most thoroughly are blood glucose and cortisol. This exploratory study is the first to investigate the effects of long gaming sessions on the biochemical parameters of healthy male adults. The extensive testing allowed us to observe short-term changes (within 6 hours), long-term changes during the duration of the gaming sessions, and follow-up after 1 week to determine whether any changes were longer lasting. In total, 9 experienced gamers completed 2 back-to-back 18-hour gaming sessions interspersed with a 6-hour rest period. All participants adhered to a structured sleep pattern due to daytime employment or attending university. Blood, saliva, and urine samples were collected from the participants every 6 hours. Linear mixed-effect models were used to analyze the repeated-measures data accumulated during the study. A total of 51 biochemical parameters were investigated. In total, 12 of the 51 biochemical parameters significantly changed during the study: alkaline phosphatase, aspartate aminotransferase, bilirubin, chloride, creatinine, glucose, hemoglobin, immature reticulocyte fraction, lactate, methemoglobin, sodium, and thrombocytes. All changes were within the normal range. The mean glucose level of the participants was 4.39 (SD 0.07) mmol/L at baseline, which increased significantly by 0.24 (SD 0.07) mmol/L per 6 hours during the first period and by 0.38 (SD 0.07) mmol/L per 6 hours in the second period (P<.001). The glucose levels during the second session increased even though the participants had little energy intake. Cortisol levels did not change significantly, although the cortisol pattern deviated from the typical circadian rhythm. During both gaming sessions, we observed increasing cortisol levels from 6 AM until noon. The participants were relatively dehydrated at the start of the study. The patients were asked to fast before the first blood sampling. Within the first 6 hours of the study, the participants rehydrated, followed by relative dehydration during the remainder of the study. This pattern was identified using the following parameters: albumin, creatinine, hemoglobin, erythrocytes, potassium, and platelets. This study is the first of its kind, and many of the analyses in the study yielded novel results. The study was designed to emulate the behavior of gamers during the weekend and other long gaming sessions. At this point, we are not able to determine the difference between the effects of gaming and behavior during gaming. Regardless, the results of this study suggest that healthy gamers can partake in long gaming sessions, with ample amounts of unhealthy foods and little rest, without acute impacts on health.

Anemia predictive indicator (API). how can we predict in three days the anemia that will develop in three months? case report

The Anemia Predictive Indicator (API) includes the analysis of the reticulocyte count, the reticulocyte hemoglobine content (HCr) and immature reticulocyte fraction (IRF). API reflects erythropoietic activity and allows immediate detection and correction of iron deficiency anemia, and the response can be observed on the second and third day after starting treatment. In this case report, a 79-year-old woman after a total knee replacement, API provided predictability at the onset of anemia, allowed the follow-up of anemia and its treatment, collaborated in clinical and medical decision, contributed to preventive actions and improve the patient's quality of life.

Immature reticulocyte fraction: A novel biomarker of hemodynamic severity in pulmonary arterial hypertension.

Various erythropoietic abnormalities are highly prevalent among patients with pulmonary arterial hypertension (PAH) and associated with worse disease severity. Given the poorly understood yet important roles of dysregulated erythropoiesis and iron metabolism in PAH, we sought to further characterize the hematologic and iron profiles in PAH and their relationship to PAH severity. We recruited 67 patients with PAH and 13 healthy controls. Hemodynamics attained within 1 year of blood sample collection were available for 36 patients. Multiple hematologic, iron, and inflammatory parameters were evaluated for their association with hemodynamics. The subset with hemodynamic data consisted of 29 females (81%). The most common etiologies were idiopathic PAH (47%) and connective tissue disease-related PAH (33%). 19 (53%) had functional class 3 or 4 symptomatology, and 12 (33%) were on triple pulmonary vasodilator therapy. Immature reticulocyte fraction (IRF) had significant positive correlations with mean pulmonary artery (PA) pressure (mPAP) (0.59, p < 0.001), pulmonary vascular resistance (0.52, p = 0.001), and right atrial pressure (0.46, p = 0.005), and significant negative correlations with cardiac index (-0.43, p = 0.009), PA compliance (PAC) (-0.60, p < 0.001), stroke volume index (SVI) (-0.57, p < 0.001), and mixed venous oxygen saturation (-0.51, p = 0.003). IRF correlated with markers of iron deficiency (ID) and erythropoiesis. On multivariable linear regression, IRF was associated with elevated mPAP and reduced SVI and PAC independent of EPO levels, transferrin saturation, and soluble transferrin receptor levels. We identified IRF as a novel and potent biomarker of PAH hemodynamic severity, possibly related to its associations with erythropoiesis, ID, and tissue hypoxia.

Reticulocyte Indexes and their Significance

A crucial diagnostic tool for assessing, categorizing, and monitoring the effectiveness of anemia treatment is the reticulocyte count. The quality of erythropoiesis is an intrinsic aspect of the pathophysiology of anemia, and the ability of reticulocyte production would be one of the pivotal factors in the quality of erythropoiesis. However, in this minireview, we explain clearly whether the reticulocyte index’s ability is associated with clinical outcomes. There are several ways to describe the reticulocyte count: as a proportion of all red blood cells, as an absolute count, as a corrected count, as the Reticulocyte Production Index (RPI), or as the Immature Reticulocyte Fraction (IRF). Reticulocyte indexes aid in determining the etiology of anemia. They can distinguish between anemia-related causes and other dyserythropoietic problems.

Reticulocytes and Related Parameters in Clinical Practice

The development of hematologic analyzers allowed us to assess several additional parameters derived in addition to the number of reticulocytes. There is, among others, the calculation of immature reticulocyte fractions, reticulocyte maturity index, reticulocyte production index, and equivalent reticulocyte hemoglobin. The advantage of the equivalent hemoglobin and the content of hemoglobin is the insensitivity to interference by inflammation. These newly introduced parameters expand the possibilities to access bone marrow erythropoietic activity, iron stores, and the effectiveness of iron supplementation, vitamin B12, and folic acid supplementation. These parameters are also used to make decisions about blood transfusions or to detect occult internal bleeding.

The Immature Reticulocyte Fraction (IRF) in the Sysmex XN-1000V Analyzer Can Differentiate between Causes of Regenerative and Non-Regenerative Anemia in Dogs and Cats.

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.

Usefulness of baseline immature reticulocyte fraction to mature reticulocyte fraction ratio (IMR) as A prognostic predictor for patients with small cell lung cancer

BackgroundSmall cell lung cancer (SCLC) has a strong invasive ability and a high degree of malignancy, so accurate prognosis prediction is crucial for making the most favorable treatment decision.Unfortunately, there is a scarcity of prognostic indicators specific to SCLC. Reticulocyte levels in blood parameters have been linked to the prognosis of various malignancies. Given SCLC's aggressive characteristics, identifying reliable prognostic markers, such as reticulocyte counts, becomes pivotal in enhancing prognostic accuracy and guiding effective therapeutic strategies. ObjectiveThis study aimed to evaluate the predictive power of the immature reticulocyte fraction (IRF) to mature reticulocyte fraction (MRF) ratio (IMR) for survival outcomes in patients with SCLC. Materials and methodsA retrospective analysis was conducted on 192 patients with small cell lung cancer (SCLC). The median values of various prognostic indicators, such as IMR, IRF, MRF, reticulocyte count (RET), SII (systemic immune-inflammatory index), were utilized as cutoff points, categorizing patients into high and low groups. The Kaplan–Meier method, univariate, multivariate analyses Cox regression, and C-index were used to analyze the prognostic factors for overall survival (OS). ResultsIn our cohort, 138 (71.9 %) were male, 119 (62 %) were smokers, and 82 (57.3 %) were older than 60 years old. The median survival time was 18.15 months.Higher mortality was observed in the high IMR and high IRF groups, while the high MRF group exhibited lower mortality. At the same time, mortality was lower in the high MRF group. Univariate analysis showed that smoking history (P = 0.006), tumor stage (P = 0.002), chemotherapy cycle (P = 0.014), IMR (P = 0.01), and many other factors significantly affected the prognosis of SCLC. Multivariate analysis demonstrated that elevated IMR was an independent adverse predictor of OS (P = 0.039, HR = 0.330). Spearman test confirmed that the prognostic indicators IRF, IMR, and SII were positively correlated with the overall survival rate of patients with SCLC. Kaplan-Meier analysis showed that the OS rate of patients with high IMR was significantly worse (P = 0.0096). In addition, we found that IMR was superior to IRF in distinguishing patients with different outcomes in the low and high groups (P < 0.05). Our novel integration index, combining IMR with the TNM stage system and SII index, exhibited superior prognostic value compared to the original index. Additionally, the combination of prognostic indicators IMR and SII significantly stratified stage I-II SCLC patients (P ＜0.05). ConclusionsThe prognostic index based on peripheral blood IMR stands out as an independent predictor for SCLC patients pre-treatment. Its accessibility through routine blood analysis facilitates immediate clinical application without requiring prolonged scientific research validation. The integration of IMR with the TNM score enhances survival prediction and risk stratification. Notably, when combined with the SII score, the new IMR index demonstrates significant improvements in prognostication for stage I-II small cell lung cancer.

Report of the International Council for Standardization in Haematology working group for standardization of reticulocyte parameters.

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. 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. 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. 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.

Associations of obesity and body shape with erythrocyte and reticulocyte parameters in the UK Biobank cohort

BackgroundObesity is associated with type 2 diabetes mellitus and chronic low-grade inflammation. Although chronic inflammatory conditions and diabetes are associated with anaemia, less is known about associations of obesity and body shape, independent of each other, with erythrocyte and reticulocyte parameters.MethodsWe investigated the associations of body mass index (BMI) and the allometric body shape index (ABSI) and hip index (HI), which are uncorrelated with BMI, with erythrocyte and reticulocyte parameters (all continuous, on a standard deviation (SD) scale) in UK Biobank participants without known metabolic, endocrine, or major inflammatory conditions (glycated haemoglobin HbA1c < 48 mmol/mol, C-reactive protein CRP < 10 mg/L). We examined erythrocyte count, total reticulocyte count and percent, immature reticulocyte count and fraction (IRF), haemoglobin, haematocrit, mean corpuscular haemoglobin mass (MCH) and concentration (MCHC), mean corpuscular and reticulocyte volumes (MCV, MRV), and red cell distribution width (RDW) in multivariable linear regression models. We additionally defined body shape phenotypes with dichotomised ABSI (≥ 73 women; ≥ 80 men) and HI (≥ 64 women; ≥ 49 men), including “pear” (small-ABSI-large-HI) and “apple” (large-ABSI-small-HI), and examined these in groups according to BMI (18.5–25 normal weight; 25–30 overweight; 30–45 kg/m2 obese).ResultsIn 105,853 women and 100,854 men, BMI and ABSI were associated positively with haemoglobin, haematocrit, and erythrocyte count, and more strongly with total reticulocyte count and percent, immature reticulocyte count and IRF. HI was associated inversely with all, but least with IRF. Associations were comparable in women and men. In groups according to obesity and body shape, erythrocyte count was ~ 0.6 SD higher for obese-“apple” compared to normal-weight-“pear” phenotype (SD = 0.31*1012/L women, SD = 0.34*1012/L men), total reticulocyte count was ~ 1.1 SD higher (SD = 21.1*109/L women, SD = 23.6*109/L men), immature reticulocyte count was ~ 1.2 SD higher (SD = 7.9*109/L women, SD = 8.8*109/L men), total reticulocyte percent was ~ 1.0 SD higher (SD = 0.48% women and men), and IFR was over 0.7 SD higher (SD = 5.7% women and men). BMI but not ABSI or HI was associated more weakly inversely with MCV, MRV, and MCH, but positively with MCHC in men and RDW in women.ConclusionsIn obesity uncomplicated with diabetes, larger BMI and ABSI are associated with increased erythropoiesis and reticulocyte immaturity.

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?

BackgroundThe effectiveness of red cell transfusion in a given blood unit that relied on both quantity and quality of donated cells undoubtedly affects prognostic outcomes. ObjectiveWe 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 methodsThis 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. ResultsFunctional 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. ConclusionSubclinical 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.

Research use only and cell population data items obtained from the Beckman Coulter DxH800 automated hematology analyzer are useful in discriminating MDS patients from those with cytopenia without MDS.

We investigated the performance of research use only/cell population data (RUO/CPD) items obtained from the Beckman Coulter DxH800 automated hematologic analyzer in discriminating MDS patients from cytopenic patients without MDS.Total of 14 routine CBC, 18 research use only (RUO) items, and 70 CPD items were obtained retrospectively at diagnosis. The results were then compared between 94 MDS patients and 100 cytopenic patients without MDS. In items with statistically significant differences, receiver operating characteristic (ROC) analysis was performed and the results were compared.Four CBC/RUO items [red cell distribution width-standard deviation (RDW-SD), immature reticulocyte fraction (IRF), mean sphered cell volume (MSCV), high light scatter reticulocytes (HLR)], and two CPD items [mean volume of neutrophils (NE-V-Mean) and mean volume of early granulated cells (EGC-V-Mean)] showed area-under the curve (AUC) scores > 0.750. Notably, four RUO/CPD items (MSCV > 81.4/HLR > 0.15%/NE-V-Mean > 145/EGC-V-Mean > 156) showed high sensitivity (91.9%/93.6%/88.1%/90.2%, respectively) in discriminating MDS patients from cytopenic patients without MDS. With these six items, scores ≥ 4 (defined as ≥ 4 items exceeding cutoff values out of six items) showed AUC scores/sensitivity/specificity/accuracy (0.891/87.3%/79.0%/83.0%, respectively).Six CBC/RUO/CPD items showed satisfactory AUC scores of > 0.750, and four RUO/CPD items showed high sensitivity in discriminating MDS patients from cytopenic patients without MDS. Scoring system with six items showed high sensitivity, specificity, and accuracy with decision criteria of ≥ 4 scores. Therefore, DxH800 RUO/CPD items would be useful in discriminating MDS patients from cytopenic patients without MDS.

Stability and comparison of complete blood count parameters between capillary and venous blood samples.

This study assessed the comparability of complete blood count (CBC) parameters between capillary and venous samples, and extended previous research by examining the influence of different storage temperatures on CBC stability up to 7 days after sample collection. Venous and capillary blood samples were collected from 93 adult patients. Hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean platelet volume (MPV), leukocytes, lymphocytes, basophils, eosinophils, erythrocytes, red cell distribution width (RDW), immature granulocytes (IG), immature reticulocyte fraction (IRF), monocytes, neutrophils, platelets, and reticulocytes were measured. Deming regression and mean relative differences between venous and capillary measurements were contrasted with desirable total allowable error (TEa). Stability was assessed in 20-27 venous blood samples stored at 4, 21-22, or 30°C, and analyzed at 0, 24, 48, 72, 96, 120, 144, and 168 h. Mean relative change with respect to baseline measurements was compared to the desirable TEa to determine acceptable stability. Deming regression demonstrated strong linear correlations and acceptable variation between venous and capillary measurements. Erythrocytes, Hb, Ht, MCH, MCV, RDW, reticulocytes, and platelets showed acceptable stability for at least 96 h at 4°C. Mean relative change exceeded desirable TEa after 24 h at 30°C for all parameters, except erythrocytes, Hb, leukocytes, and MCH. Clinical laboratory specialists and clinicians should be aware of potential differences between venous and capillary measurements, and the influence of storage conditions. Clinical validity of delayed CBC analysis depends on the clinical situation and required precision of the result.

Eritropoez için Yeni Bir Parametre: Kordon Kanında Immatür Retikülosit Fraksiyon Değerlerinin Klinik Faktörlerle İlişkisi ve Yenidoğan için Referans Değerleri

Aim: The immature reticulocyte fraction (IRF) is a new parameter for the reticulocyte maturity index, representing an independent parameter of erythropoiesis that may be useful to better assess erythropoietic activity in neonates. In this study, the relationship between IRF values and clinical features in newborns was investigated and reference values were obtained. Material and Methods: Newborns between 28-40 weeks of gestation were included in this prospective study. At birth, maternal venous and cord blood samples were obtained for measurements of complete blood count (CBC), blood gases, and plasma concentrations of various biochemical parameters. Results: A total of 123 newborns, 99 term and 24 preterm, were included in the study. When the laboratory characteristics of the premature and term babies were compared according to their gestational weeks, while the median IRF value of cord blood was higher in term babies than in premature babies (p=0.039), other laboratory findings did not differ significantly. The median IRF value was 0.52 (range, 0.15-1.00) in term infants and 0.34 (range, 0.16-0.76) in preterm infants. IRF reference values for the term and preterm newborns were determined in cord blood. Moderately positive correlations were observed between the IRF levels and both the RDW (r=0.423, p&amp;lt;0.001) and the CRP (r=0.389, p&amp;lt;0.001) levels. Conclusion: The results of this study showed that newborns' IRF values were not affected by maternal variables and changed with the week of birth. The results of this study might be considered a guide for future studies using IRF value in newborns.

Changes in Immature Reticulocytes Aid the Indirect Detection of Microdose Recombinant Erythropoietin Use in Men and Women.

We investigated whether immature reticulocyte fraction (IRF) and the immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive and specific biomarkers for microdose recombinant human erythropoietin (rHuEPO) and whether the inclusion of reticulocyte percentage (RET%) and the algorithm "abnormal blood profile score (ABPS)" increased the athlete biological passport (ABP) sensitivity compared with hemoglobin concentration ([Hb]) and the OFF-hr score ([Hb]-60 × √RET%). Forty-eight (♀ = 24, ♂ = 24) participants completed a 2-wk baseline period followed by a 4-wk intervention period with three weekly intravenous injections of 9 IU·kg -1 ·bw -1 epoetin β (♀ = 12, ♂ = 12) or saline (0.9% NaCl, ♀ = 12, ♂ = 12) and a 10-d follow-up. Blood samples were collected weekly during baseline and intervention as well as 3, 5, and 10 d after treatment. The rHuEPO treatment increased [Hb] (time-treatment, P < 0.001), RET% (time-treatment, P < 0.001), IRF (time-treatment, P < 0.001) and IR/RBC (time-treatment, P < 0.001). IRF and IR/RBC were up to ~58% ( P < 0.001) and ~141% ( P < 0.001) higher compared with placebo, and calculated thresholds provided a peak sensitivity across timepoints of 58% and 54% with ~98% specificity, respectively. To achieve >99% specificity for IRF and IR/RBC, sensitivity was reduced to 46% and 50%, respectively. Across all timepoints, the addition of RET% and ABPS to the ABP increased sensitivity from 29% to 46%. Identification of true-positive outliers obtained via the ABP and IRF and IR/RBC increased sensitivity across all timepoints to 79%. In summary, IRF, IR/RBC, RET% and ABPS are sensitive and specific biomarkers for microdose rHuEPO in both men and women and complement the ABP.

Use of Immature Reticulocyte Fraction in Clinical Settings

Use of Immature Reticulocyte Fraction in Clinical Settings

Is post-transplant day + 14 immature reticulocyte fraction (IRF) a reliable surrogate marker for predicting early platelet engraftment in pediatric hematopoietic stem cell transplant?

BackgroundProphylactic platelet transfusion is given to patients when the platelet count is less than ten thousand to prevent clinically significant bleeding till platelet engraftment is documented. Despite a very low platelet count, if platelet engraftment is confidently predicted, then platelet transfusion can be avoided in an otherwise stable patient.ObjectiveTo determine the role of post-transplant day + 14 immature reticulocyte fraction (IRF) and immature platelet fraction (IPF) as surrogate markers for early prediction of platelet engraftment in pediatric hematopoietic stem cell transplant patients.Material and methodsThis prospective study was done at the National Institute of Blood Diseases and Bone Marrow Transplantation between January 2017 and December 2020. A total of 56 and 31 patients were enrolled in the deviation and validation cohorts respectively. IPF and IRF were tested on a Sysmex XN-1000 hematology analyzer on days + 14 and + 21 of the bone marrow transplant. Platelet count on day + 14 and the day of engraftment was documented. Spearman correlation analysis and receiver operating characteristic curve (ROC) calculation were done using the statistical package STATA version 12, to determine IRF and IPF cut-off values to predict a median platelet engraftment day.ResultsThe derivation and validation cohorts were statistically comparable. The area under the receiver operating characteristic curve (ROC) for IPF and IRF was 0.53 (95% CI: 0.37 – 0.68, p = 0.750) and 0.74 (95% CI: 0.61 – 0.89, p = 0.001) respectively. A weak inverse correlation (rs0.36, p = 0.007) between IRF and platelet engraftment day was found. The ROC demonstrated that the cut-off value for Day + 14 IRF of 13% has a sensitivity and specificity of 92.9% and 37% respectively. This finding was confirmed in the validation group with sensitivity and specificity of 88.2% and 45.2% respectively.ConclusionThis study found that Day + 14 IRF but not IPF value can reliably predict platelet engraftment by day + 17 post-transplant.

Clinical utility of immature reticulocyte fraction for identifying early red blood cell regeneration in anemic dogs.

Evaluating regeneration is essential for the classification and differential diagnosis of anemia in dogs. Early detection of regeneration is challenging in anemic dogs. This study assessed the value of immature reticulocyte fraction (IRF) in differentiating preregenerative anemia (PRA) from nonregenerative anemia (NRA) in dogs. Ninety-four dogs: 49 controls and 45 with anemia. Case-control study. Fractions of low-, medium- (MFR), and high-fluorescence reticulocytes (HFR), were measured using the ADVIA 2120i hematology analyzer. The IRF was calculated as the sum of percentages of MFR and HFR. Data from dogs with regenerative anemia (RA, n=19), PRA (n=11), and NRA (n=15) were retrospectively analyzed. The value of IRF was compared with reticulocyte production index (RPI) using the receiver operating characteristic (ROC) curve. The median of IRF was significantly higher in dogs with RA (46.5%; range, 40.9-53.6%; P < .001) and PRA (40.6%; range, 27.7-47.1%; P=.01) than in controls (22.1%; range, 16.9-29.3%). The IRF in dogs with PRA showed no difference compared to dogs with RA (P > .99) but was higher than dogs with NRA (18.7%; range, 8.8-24%; P=.00). The area under the ROC curve of IRF was superior to that of RPI (0.897 vs 0.818, P=.00) in differentiating dogs with PRA from NRA. The IRF is a reliable variable for detecting early regeneration in anemic dogs without reticulocytosis. The study suggests that the measurement of IRF could be useful in classifying anemic dogs.