Mean Hb Research Articles

Impact of use of iron fortified iodised salt beyond 12 months on haemoglobin levels

Background: Use of iron fortified iodised salt (IS) for 12 months, resulted in improvement in haemoglobin (Hb) in women, children and men. There is no published data on impact of DFS use beyond 12 months on Hb levels. Methods: A community based open randomised study to assess impact of use of DFS on Hb was discontinued after 12 months due to COVID 19 related lockdown. These families used IS for six months during lockdown; they were willing to continue using the salt provided for further one year. These families were re-randomized into three groups and given the assigned salt for further 12 months and Hb, ferritin and C-reactive protein (CRP) were estimated at 12 months. Results: Improvement in the mean Hb was 0.5 g/dl in women who had used IS earlier and DFS under second randomisation and 0.3 g/dl in those who had used DFS under first and second randomisation. Mean Hb at 30 months was higher in those who had used DFS for 24 months as compared to those who had used IS for 18 months and DFS for 12 months. The deterioration in mean Hb following discontinuation of DFS for 6 and 18 months was small. Conclusions: DFS use for the second year resulted in a further increase in Hb in those who had used DFS earlier. The relatively small deterioration in mean Hb following discontinuation of DFS might at least be in part due to the impact of nutrition and health education and access to health and nutrition services.

EFFECT OF BEETROOT JUICE ON THE INCREASE IN HEMOGLOBIN LEVELS AMONG PREGNANT WOMEN AT KEMILING INPATIENT COMMUNITY HEALTH CENTER IN 2022

Anemia in pregnancy is a hemoglobin level below 11gr% in the 1st and 3rd trimesters or <10.5g% in the 2nd trimester. The pharmacological method to treat anemia is by administering Fe tablets and folic acid, while non-pharmacological treatment and prevention of anemia can be done by consuming beetroot. This study aims to determine the effect of beetroot juice on the increase in hemoglobin levels among pregnant women at Kemiling Inpatient CHC in 2022. This was a quantitative quasi-experimental study with one group pre-test and post-test approach. The samples involved 15 pregnant women in the third trimester with mild or moderate anemia at Kemiling Inpatient CHC. The study was conducted in January 2022. Data was collected using observation sheets. Data were analyzed using univariate and bivariate analysis (t-test). The results showed that the mean Hb level before and after the administration of beetroot juice was 10.46 gr/dl and 11.70 gr/dl, respectively. There was an effect of beetroot juice on the increase in hemoglobin levels among pregnant women at Kemiling Inpatient CHC in 2022 with a p-value of 0.000. Pregnant women need to find information about prevention and management of anemia in pregnancy and have regular prenatal checkups.

The effectiveness of oral bovine lactoferrin compared to iron supplementation in patients with a low hemoglobin profile: A systematic review and meta-analysis of randomized clinical trials

BackgroundPatients with a low serum blood hemoglobin concentration suffer from a pathologic state that contributes significantly to morbidity and mortality figures worldwide. Oral iron supplementation, the most common method of treatment, is reported to have poor patient adherence, due to its unwanted side effects. Lactoferrin is a globular glycoprotein of the transferrin family that has shown promising results in patients with a low hemoglobin profile. This systematic review and meta-analysis of randomized clinical trials explore its effect on blood hemoglobin compared to conventional iron preparations.MethodsWe followed the PRISMA Guidelines for reporting systematic reviews and meta-analyses. A systematic search was conducted in electronic databases (PubMed, CINAHL, Scopus, and Cochrane) from inception to June 2022. Meta-analysis was performed on studies where the primary outcome was the mean Hb concentration, comparing lactoferrin to ferrous sulfate subgroups. We assessed the methodological quality of the trials using the Jadad scoring scale.ResultsNineteen trials published between 2006 and 2022 met the eligibility criteria. It has been found that the levels of Hb concentration in different populations with varying health conditions undergo a moderate to significant change after treatment with all types of trialed interventions, including both iron and lactoferrin treatment, in both the intervention group and the comparison group. Most of the studies report that LF showed a statistically significant increase in Hb concentration levels, compared to those in the iron group. The meta-analysis included seven trials comparing the effectiveness of lactoferrin to ferrous sulfate for patients with low Hb concentration. The analysis showed a statistically significant increase in Hb levels in the oral bovine lactoferrin group compared to ferrous sulfate (SMD -0.81, 95% CI: -1.21, -0.42, p < 0.0001, I2 = 95.8%, P heterogeneity < 0.001).ConclusionsLactoferrin is an effective intervention at doses of 100–250 ng/day, for patients with a low Hb concentration. As a safer option and with high compliance evidence, lactoferrin can serve as an iron replacement treatment for patients who may be experiencing adverse side effects due to iron intake.

Ultrasound-guided percutaneous nephrolithotomy versus conventional c-arm-guided percutaneous nephrolithotomy: a prospective randomized comparative study

BackgroundUltrasound guidance for renal access in percutaneous nephrolithotomy (PCNL) is a safe, effective, and low-cost procedure. The current study compared the safety and effectiveness of ultrasound-guided PCNL (US-PCNL) for renal stone therapy versus fluoroscopy-guided PCNL (FL-PCNL) in prone position.ResultsSuccessful puncture was attained in all cases in both groups. Unlike fluoroscopy, US guidance reduced the time needed for achieving renal puncture that was (22.45 ± 6.95 s) compared to fluoroscopy that was (68.28 ± 56.76 s) (P value < 0.001). The mean duration of access that was reported in our study was (3.92 ± 0.72 min) in the US-PCNL group and (4.03 ± 0.77 min) in the FL-PCNL group (P value 0.460). There was no significant difference in the total operative time between both groups in our study as the mean operative time in the US-PCNL group was (61.47 ± 6.07 min) and (65.86 ± 20.86 min) in the FL-PCNL group with a (P value of 0.349). Stone-free rate was nearly similar in both groups (P value 0.336). Three cases in our study in the FL-PCNL group had bleeding that required blood transfusion post-operative; mean Hb change was 0.23 g/dL and 0.55 g/dL in US-PCNL and FL-PCNL groups, respectively, which is clinically irrelevant despite statistical significance (P value 0.007). Mean fluoroscopy time was (6.38 ± 3.84) minutes in FL-PCNL group.ConclusionUltrasound guidance is a reliable tool in the hands of experienced urologists in performing PCNL with less or even zero radiation.

Cost-effectiveness analysis of parenteral iron therapy compared to oral iron supplements in managing iron deficiency anemia among pregnant women.

This study compared the clinical efficacy and cost-effectiveness of parenteral iron, using intravenous iron sucrose (IVIS) therapy against the standard regimen of oral iron (OI) therapy for managing iron-deficiency anemia (IDA) among pregnant women in a natural primary care setting in Gujarat. A prospective cost-effectiveness study was conducted in natural programme setting wherein 188 pregnant women in their 14 to 18weeks with moderate and severe anemia women enrolled from two districts of Gujarat, and 142 were followed up until the post-partum phase. The intervention group comprised of 82 participants who were administered IVIS, while the comparison group comprised of 106 participants who were put on OI therapy. Hemoglobin (Hb) levels were measured at periodic intervals, first during enrollment and then during each month of pregnancy period and finally on the 42nd day of the post-natal period. Change in mean Hb level from baseline was the primary outcome, while the incidence of morbidity and mortality was a secondary outcome measure. The intervention group showed a significant incremental mean change in Hb level from 8.2g/dl to 11.45g/dl at the fourth follow-up, while the control group's mean Hb level reduced from 9.99g/dl to 9.55g/dl. The discounted cost per beneficiary for IVIS was US$ 87, while that for OI was US$ 49. The incremental cost-effectiveness ratio (ICER) was US$ 9.84, which is 0.049% of India's per capita GDP. IVIS therapy was more clinically effective and cost-effective than OI therapy among pregnant women for management of moderate and severe anemia.

Exposure to tobacco (Nicotiana tabacum) extract and cigarette smoke induces hematological and histopathological alterations in Swiss albino mice

Tobacco smoking is a widely practiced recreational activity and is associated with numerous health risks. Hence, the present study was conducted on Swiss albino mice to assess the impact of aqueous extract of tobacco and cigarette smoke on behavioral, hematological, and histopathological parameters of the lungs, liver, and kidney. The mice were divided into Control (Cont), Tobacco nicotiana (TN), and Cigarette smoke (CS) groups (n=6). TN group received aqueous tobacco orally at a dose of 5ml/kg BW for 21 days, whereas CS group was exposed to inhalational commercial cigarette smoke for the same duration. On day 22, blood samples and visceral organs were collected to evaluate hematological (TEC, TLC, Hb%) and histopathological parameters from euthanized mice. The TEC values were significantly elevated (P&lt;0.05) in both groups. In contrast to the control group, the TLC value was lower in the CS group (P&gt;0.05) than in the TN group, but the mean Hb% values showed no significant changes. Lower body weight, aggressive behavior, and weakness were observed in the treated groups. Histopathologically, the lung revealed emphysematous changes, alveolar septal thickening, inflammatory cells infiltration, congestion, and thrombus formation in pulmonary artery. Liver exhibited hepatocyte degeneration with karyomegaly and karyorrhexis, derangement of hepatic cords and sinusoids with central vein congestion. Derangement of renal tubules, edema, and glomerular degeneration observed in the kidney. These observations lead us to postulate that tobacco and cigarette smoke exert detrimental effects on the structure of some vital organs in the body after direct or indirect uptake.

Third-generation sequencing identified two rare α-chain variants leading to hemoglobin variants in Chinese population.

Rare and novel variants of HBA1/2 and HBB genes resulting in thalassemia and hemoglobin (Hb) variants have been increasingly identified. Our goal was to identify two rare Hb variants in Chinese population using third-generation sequencing (TGS) technology. Enrolled in this study were two Chinese families from Fujian Province. Hematological screening was conducted using routine blood analysis and Hb capillary electrophoresis analysis. Routine thalassemia gene testing was carried out to detect the common mutations of α- and β-thalassemia in Chinese population. Rare or novel α- and β-globin gene variants were further investigated by TGS. The proband of family 1 was a female aged 32, with decreased levels of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), Hb A2, and abnormal Hb bands in zone 5 and zone 12. No common thalassemia mutations were detected by routine thalassemia analysis, while a rare α-globin gene variant Hb Jilin [α139(HC1)Lys>Gln (AAA>CAA); HBA2:c.418A>C] was identified by TGS. Subsequent pedigree analysis showed that the proband's son also harbored the Hb Jilin variant with slightly low levels of MCH, Hb A2, and abnormal Hb bands. The proband of family 2 was a male at 41 years of age, exhibiting normal MCV and MCH, but a low level of Hb A2 and an abnormal Hb band in zone 12 without any common α- and β-thalassemia mutations. The subsequent TGS detection demonstrated a rare Hb Beijing [α16(A14)Lys>Asn (AAG>AAT); HBA2:c.51G>T] variant in HBA2 gene. In this study, for the first time, we present two rare Hb variants of Hb Jilin and Hb Beijing in Fujian Province, Southeast China, using TGS technology.

Prevalence of Anemia among Adult Male Camel Milk Consumers and Nonconsumers in Rural Rajasthan: A Community-based Cross-sectional Study

Introduction: Anemia is an important nutritional disorder with major public health importance. In India, anemia prevalence among adult males was 25.0% (NFHS-5, 2020–2021). Being rich in iron and other micronutrients camel milk might decrease the nutritional anemia prevalence. The objective was to determine the prevalence of anemia among adult male camel milk consumers (CMC) versus nonconsumers in rural Rajasthan. Materials and Methods: A community-based study was conducted among 30 CMC adult male. All the participants meeting the eligibility criteria were recruited. The same numbers of non-CMC (NCMC) adult males were recruited with respect to similar age, sex, and residence. After obtaining informed consent a semi-structured interview schedule containing sociodemographic, dietary characteristics were introduced to all participants in June 2013. The participants were assessed for their hemoglobin (Hb) level from fingertip capillary blood using the Cyanmet Hb method as suggested by Dacie and Lewis. The prevalence of anemia in each group was compared. Data were entered into Microsoft Excel version 2013 and analyzed in Stata version 13. Results: The prevalence of anemia was more (26.6%) among nonconsumers than CMCs (16.6%). There was a significant difference between these groups (P &lt; 0.001). The mean (standard deviation) Hb (g/dL) level of the male in the CMC and NCMC categories was found to be 13.0 (0.99) and 12.22 (1.51) in adult males, respectively. This difference was statistically significant (P = 0.021). Conclusion: The prevalence of anemia among CMC adult males was lower than nonconsumers with relatively higher levels of Hb in the former group. Future studies are recommended for further inference.

Roxadustat for Treating Anemia in Patients with Advanced Chronic Kidney Disease Not Undergoing Dialysis: A Retrospective Study.

Objective Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, increases the hemoglobin (Hb) levels in patients with chronic kidney disease (CKD). To date, limited clinical studies have focused on the excessive increase in the Hb levels in the early weeks after switching from erythropoiesis-stimulating agents (ESA) to roxadustat in adult non-dialysis patients. We conducted a retrospective study to examine whether early overshoot frequently occurs after switching to roxadustat. Methods This 8-week retrospective pilot study examined patients with anemic, non-dialyzed CKD who switched from ESA (darbepoetin or epoetin beta pegol) to roxadustat or continued ESA. The Hb levels >12.5 g/dL after starting our observation was defined as Hb overshoot. Patients: Twenty-three patients who switched to roxadustat (roxadustat group) and 63 who continued ESA (ESA group) were included. Results The baseline median estimated glomerular filtration rate and mean Hb levels were 15.7 mL/min/1.73 mShizuokax and 10.77 g/dL in roxadustat group and 15.2 mL/min/1.73 m2 and 10.64 g/dL in ESA group, respectively. Eight patients (34.8%) in the roxadustat group and two patients (3.2%) in the ESA group had Hb overshoot within the 8-week visit (odds ratio: 20.2 [95% confidence interval 3.13-130.0, p<0.01] in the background adjusted model). Among the patients with Hb overshoot in the roxadustat group, the Hb levels were maintained close to baseline 4 weeks after roxadustat discontinuation. A younger age and higher baseline Hb and Hct levels were risk factors for Hb overshoot. Conclusions Hb overshoot was frequently observed in patients switched to roxadustat. Clinicians should be aware of Hb overshoot and emphasize the importance of early Hb level checks.

Performance analysis of point-of-care testing haemoglobin concentration methods with automated haematology analyser amongst blood donors

Abstract Background: In terms of rapidness, testing methodology and sensitivity, point-of-care (POC) testing devices provide quality in haemoglobin (Hb) check for safe donation of blood. Methods: This was a prospective observational study in a tertiary care centre. Capillary finger-prick samples obtained from 100 blood donors were analysed prior to donation using reagent-free cuvettes (DiaSpect Tm), digital haemoglobinometer (True Hb) and Hb photometer (HemoCue 301). Venous samples were drawn for analysis on haematology analyser. Donors were accepted based on copper sulphate method acceptance criteria. The performance of the devices was evaluated considering automated haematology analyser (Sysmex XN 1000) as the gold standard. Results: The mean Hb value using Sysmex XN 1000, HemoCue 301, DiaSpect Tm and True Hb were 14.8 ± 1.1 g/dL, 15.4 ± 1.8 g/dL, 15.3 ± 1.8 g/dL and 18.6 ± 2.8 g/dL, respectively. The sensitivity of True Hb, DiaSpect Tm, HemoCue 301 and copper sulphate method were 96.8%, 96.8%, 3.7% and 98.9%, respectively. DiaSpect Tm had a specificity of 60% whereas specificity of True Hb and copper sulphate method were 20% each. True Hb, HemoCue 301, DiaSpect Tm and copper sulphate had a positive predictive value of 95.8%, 94.7%, 97.9% and 95.9% and accuracy of 93%, 89%, 95% and 95%, respectively. The mean turnaround time was 1 sec for DiaSpect Tm whereas 35.3 sec and 2.6 sec for True Hb and HemoCue 301, respectively. The copper sulphate test provided the highest rate of donor’s acceptance, despite unacceptable Hb levels. Conclusions: DiaSpect Tm has the advantage of rapid turnaround time, high specificity and accuracy when compared to gold standard method.

Association of Higher Hemoglobin Level With Significant Carotid Artery Plaque in the General Population.

Serum hemoglobin (Hb) level affects the viscosity of blood. Several studies have reported that Hb level is associated with adverse cardiovascular outcome. However, there is a paucity of evidence on the association between serum Hb level and the risk of subclinical atherosclerosis. Thus, the objective of this study was to investigate the relationship between Hb level and risk of carotid plaque in a health checkup cohort. This retrospective study analyzed a total of 3,805 individuals without history of cardiovascular disease (CVD) who underwent carotid ultrasonography (USG) between January 2016 and June 2018. Participants were divided into 4 groups based on Hb quartiles in each of male and female. Carotid plaque score was calculated based on USG reports. Multivariable logistic regression analysis was performed for each index of quartile groups regarding the risk of carotid plaque. Of 3,805 individuals (mean age, 52.62±10.25 years; 2,674 [70.28%] males), mean Hb level was 15.11±0.75 g/dL in male and 13.35±0.74 g/dL in female. When the Q1 group was compared to the Q4, increasing quartile of Hb was associated with the presence of significant carotid plaque (plaque score ≥3) in male (adjusted odds ratio [OR], 1.538; 95% confidence interval [CI], 1.182-2.001; p=0.001) and female (adjusted OR, 1.749; 95% CI, 1.058-2.676; p=0.01). A high Hb level is associated with an increased risk of carotid plaques in individuals without history of CVD. This finding may support the need for early screening of CVD in individuals with high Hb levels.

The importance of intensive follow-up and achieving optimal chronic antithrombotic treatment in hospitalized medical patients with anemia: A prospective cohort study

BackgroundAnemia is a global health concern, particularly among the elderly on chronic antithrombotic treatment. Close monitoring of hemoglobin (Hb) levels and achievement of an optimized treatment significantly enhance patients’ quality of life. This study aimed to examine the impact of antithrombotic treatment on Hb levels and readmissions in hospitalized patients with anemia. MethodsThis is a prospective cohort study of patients admitted to the Department of Internal Medicine of the University Hospital of Heraklion, Greece, from November 2021 to October 2022 with the diagnosis of anemia while receiving antithrombotic treatment. Data regarding demographics, past medical history, and laboratory and endoscopy findings were recorded. For those receiving inappropriate therapy according to international guidelines, antithrombotic treatment was optimized. Subsequent follow-ups occurred at one and six months post-discharge. Six- and twelve-month anemia-caused readmissions, as well as annual mortality, were evaluated. ResultsIn total, 104 patients were assessed. Among them, 34.6% were on antiplatelets, 56.7% were on anticoagulants, and 8.7% were on combination treatment. The mean age was 80 ± 8.2 years, and 54.8% were males. On admission, mean Hb levels were 6.86 ± 1.23 g/dL, while 56 (53.8%) patients had severe anemia. Gastroscopy and colonoscopy were performed in 75.0% and 41.4% of patients, respectively, confirming gastrointestinal bleeding in most of the cases. Treatment optimization was carried out for 56 patients. Follow-up revealed elevated Hb levels after one and six months post-discharge, while anemia-related readmissions stayed below 10%. ConclusionsMost hospitalized anemic patients on antithrombotic treatment had endoscopic findings favoring gastrointestinal bleeding. Half received inappropriate antithrombotic therapy. Treatment optimization and regular follow-up improved Hb levels and reduced readmissions.

Maternal Hemoglobin Levels as a Causative Factor in Incidence of Low Birth Weight Babies: A Public Health Prospective

Aims: To analyze some aspects of the maternal and the newborn in the incidence of low birth weight babies (LBWB).&#x0D; Study Design: simple retrospective with cross-sectional design approach.&#x0D; Place and Duration of Study: Retrospective data of LBWB obtained from newborn medical record (year 2017-2022) of The Sultan Thaha Saifuddin Tebo Regional Public Hospital, located in Jambi-Indonesia and analysis conducted in the Departemen Kedokteran Komunitas (Community Medicine), the Faculty of Medicine, Universitas Kristen Indonesia, Jakarta Indonesia, between September-November 2023.&#x0D; Methodology: The inclusion criteria focus on all newborn with LBWB that have complete medical record data. The acquired data regarding (1) maternal age, gestational age at the time of giving birth, Hb level prior to delivery, (2) newborn: gender, survivability and birth weight. All respondents will be subjected to statistical analysis using the SPSS programme and Microsoft Excel 2016. The exhibited information consists of data distribution presented in the form of tables and utilising univariate analysis and regression testing.&#x0D; Results: Analysis of 256 LBWB data (122 (47.65%) boys, 134 (52.34%) girls) revealed that in the maternal side mean age 28.54 years old, mean gestational age 36.07 weeks at the time of giving birth and mean Hb level 10.8 gram/dL. In the newborn side viability were 226 (88.33%) viable and mean overall birth weight 1990.2 g. Statistically using Pearson correlation, there is a very weak correlation firstly among maternal Hb count with the neonates primary weight (P = 0.00, r = 0.154) and secondly between gestational age and the birth weight of newborn (P = 0.00, r = 0.000). From the community medicine perspective, Efforts to increase the Hb levels of pregnant women theoretically can be carried out more easily by encouraging and increasing the mother's and also their partners, families and society awareness of carrying out routine antenatal care, encouraging the role of health motivator/local health cadre and conducting Hb examination as simple screening; all of them supported by the government.&#x0D; Conclusion: Maternal low Hb count and gestational age correlate with birth weight of newborn. Further in depth and extensive study needed to explore specific factors contribute to the incidence of anemia in mother who gave birth neonates which have low birth weight (LBW) and their impact to pregnancy.

A transparent synthetic peptide hydrogel as a haemostatic agent in athermal nerve sparing robot-assisted radical prostatectomy: an observational study.

PuraStat® is a new synthetic haemostatic agent constituting peptides that self-assemble into sheets when exposed to ionic charges. The objective of this submission is to assess the perioperative, functional and user-reported outcomes of PuraStat® as an athermal topical haemostatic agent for use on the neurovascular bundle (NVB) in robot-assisted radical prostatectomy (RARP), and to inform further research into this developing field. Demographic and disease data for 29 consecutive patients undergoing RARP were recorded. PuraStat® was used as the primary haemostatic agent to the NVB, without thermal or suture haemostasis, unless necessary. Preoperative, 1-h postoperative and 24-h postoperative haemoglobin (Hb) were measured. Operative data including postoperative complications up to 30 days were noted. Urinary function, continence and erectile function (EF) were measured pre- and postoperatively with the International Prostate Symptom Score (IPSS), patient reporting of pad usage, and International Index of Erectile Function (IIEF)-5 respectively. A qualitative assessment of PuraStat® was made intraoperatively by the surgical assistant in the following categories: transparency, haemostatic efficacy, ready-to-use, handling, and overall satisfaction. Twenty-nine males aged between 49 and 75 years underwent a nerve-sparing RARP under a single surgeon for clinically significant prostate cancer with PuraStat® used as the primary haemostatic agent at the NVB. One patient required an additional haemostatic suture. The median prostate volume was 36 mL. Mean blood loss was 363 mL. The mean Hb at 1 and 24 h postoperative was 135.2 and 125.1 mg/dL. Median Hb change from 1-24 h postoperative was 11 mg/dL. No transfusions were required, and there were no postoperative complications. Urinary function and continence were preserved. EF in our series was lower than published data. Our observational study suggests that PuraStat® is a safe haemostatic agent in RARP with similar perioperative bleeding outcomes, comparable long-term urinary outcomes and a high level of intraoperative user satisfaction. The effects on EF requires further investigation. PuraStat® appears to be a useful therapeutic tool for the urologist performing RARPs.

Haemoglobin thresholds for transfusion: how are we doing in the era of Choosing Wisely? A retrospective cohort study.

Clinical practice guidelines and the Choosing Wisely initiative launched in 2012 recommend a haemoglobin (Hb) threshold of 70-80 g/lfor red blood cell (RBC) transfusions in stable hospitalised patients. Data on transfusion practices and their trends in medical inpatients are limited. To address this gap, we investigated transfusion practices and their trends in general internal medicine and other clinics. This retrospective cohort study analysed data from all hospitalisations with RBC transfusions at a Swiss university hospital between 2012 and 2019. We included all first transfusion episodes if pretransfusion Hb was available. The primary endpoint was mean pretransfusion Hb; secondary endpoints included potentially inadequate transfusions (i.e., transfusions at Hb ≥80 g/l) and receipt of a single RBC unit. Trends in mean pretransfusion Hb over time were estimated using generalised estimating equations, and risk factors for potentially inadequate transfusions were identified using multivariable adjusted generalised estimating equations models. Of 14,598 hospitalisations with RBC transfusions, 1980 (13.6%) were discharged from general internal medicine. From 2012 to 2019, mean pretransfusion Hb decreased from 74.0 g/l to 68.8 g/l in general internal medicine (mean annual decrease -0.76 g/l, 95% confidence interval [CI] -0.51 to -1.02) and from 78.2 g/l to 72.7 g/l in other clinics (mean annual decrease -0.69, 95% CI -0.62 to -0.77; p for interaction 0.53). The overall proportion of potentially inadequate transfusions was 17.8% in general internal medicine and 24.1% in other clinics (p <0.001) and decreased over the study period from 26.9% to 5.5% in general internal medicine and from 37.0% to 15.2% in other clinics. In contrast, the proportion of cases receiving a single RBC unit increased (39.5% to 81.4% in general internal medicine, 42.7% to 66.1% in other clinics). Older age (adjusted odds ratio [aOR] 1.45, 95% CI 1.32-1.58 for ≥65 vs <65 years), having surgery (aOR 1.24, 95% CI 1.14-1.36), acute haemorrhage (aOR 1.16, 95% CI 1.02-1.33), chronic heart failure (aOR 1.17, 95% CI 1.04-1.32), ischaemic heart diseases (aOR 1.27, 95% CI 1.15-1.41), chronic pulmonary diseases (aOR 1.24, 95% CI 1.08-1.42), malignancy (aOR 1.11, 95% CI 1.01-1.21), and rheumatic disease (aOR 1.27, 95% CI 1.01-1.59) were risk factors for potentially inadequate transfusions. More restrictive transfusion practices were adopted in general internal medicine and other clinics over time, suggesting that guideline recommendations and the Choosing Wisely initiative may have been increasingly followed. Interventions to reduce potentially inadequate transfusions should target providers who care for older patients and those with surgery or chronic cardiac and pulmonary diseases.

The Optimal Threshold for Hemoglobin S Percent Level While Performing Regular Blood Transfusion Therapy to Prevent Severe Vaso-Occlusive Pain Events in Children with Sickle Cell Anemia: A Secondary Data Analysis of Participants in the SIT Trial

Introduction: Children with sickle cell disease (SCD) often experience frequent severe acute vaso-occlusive pain events, unresponsive to FDA-approved therapies (hydroxyurea, L-glutamine, crizanlizumab) to decrease the severe acute vaso-occlusive pain event incidence rate. The ASH guidelines for pain management recommend regular blood transfusion therapy after FDA-approved therapies have failed to decrease the high rate of severe acute vaso-occlusive pain events ( The Journal of Pediatrics, 139(6), 785-789). However, unlike regular blood transfusion therapy for primary and secondary stroke prevention, for which the goal hemoglobin S (Hb S) level is ≤ 30% , no optimal Hb S threshold has been established to attenuate the severe acute vaso-occlusive pain event incidence rate. We tested the hypothesis that among children receiving regular blood transfusion therapy with a goal to keep the mean hemoglobin S level &amp;lt; 30%, participants that achieved a mean Hb S level &amp;lt; 30% would have lower rates of severe acute vaso-occlusive pain events requiring hospitalization than children regularly transfused with mean Hb S level &amp;gt; 30%. Evidence to support our hypothesis would provide the first evidence-based guidelines for the optimal hemoglobin S threshold to decrease the acute vaso-occlusive pain event incidence rate in children with sickle cell anemia (HbSS). Methods: The SIT trial was a single-blind clinical trial( Blood Advances, 4(12), 2656-2701), where participants were children with sickle cell anemia randomly allocated to receive regular blood transfusion therapy (transfusion group) or standard care (observation group). Participants receiving regular blood transfusion therapy from the SIT Trial were included in the secondary analysis. Eligibility criteria include participants between 5 and 15 years of age, with no history of stroke, one or more silent cerebral infarcts on magnetic resonance imaging, and a neurologic examination showing no abnormalities. The transfusion therapy goal was to keep the maximum Hb S level &amp;lt; 30%. For the ancillary study, participants were included only in the transfusion arm of the trial. The primary endpoint of this ancillary study was the incidence rate of hospitalization for vaso-occlusive pain episodes among those receiving only regular blood transfusion therapy. We conducted a zero-inflated negative binomial regression analysis to determine the association between the incidence rate for severe acute vaso-occlusive pain events requiring hospitalization and independent covariates, including age at the time of random allocation, sex, and mean hemoglobin S level (&amp;lt; 30% and &amp;gt; 30%). Results: A total of 90 participants received regular blood transfusion therapy in the SIT trial. Among participants transfused, 53 and 37 individuals had a mean Hb S level of &amp;lt; 30% and &amp;gt; 30%, respectively. The median time on transfusions for the groups with Hb S levels of &amp;lt; 30% and &amp;gt; 30% was 2.9 years for both groups. Among the participants, 10.8% (4/37) who had a mean Hb S &amp;lt; 30% and 20.8% (11/53) of those with a mean Hb S &amp;gt; 30% experienced at least one hospitalization for a severe acute vaso-occlusive pain event. The mean hemoglobin S levels in the &amp;lt; 30% and &amp;gt; 30% groups were 25.4% and 37.5%, respectively. The mean hospital rates for severe acute vaso-occlusive pain events in the two groups &amp;lt; 30% and &amp;gt;30% were 9.4 (95% confidence interval 9.4 - 17.2 person-years) and 29.2 per 100 person-years (95% confidence interval, 21.0 - 39.5 person-years), respectively, P = 0.078. In the multivariable analysis, the incidence rate ratio for severe acute vaso-occlusive pain events showed that there was no statistical difference between those with a mean Hb S level in groups &amp;lt; 30% and &amp;gt; 30%, 0.65; P=0.43. Children with a higher baseline hemoglobin level were more likely to achieve a mean hemoglobin S level &amp;lt; 30%. Conclusion: In children with sickle cell anemia, receiving regular blood transfusion therapy with the goal of keeping the mean hemoglobin S level &amp;lt; 30%, achieving a mean hemoglobin S level &amp;gt; 30% was as effective as a mean hemoglobin S level &amp;lt; 30 % in decreasing the incidence rate of severe acute vaso-occlusive pain events requiring hospitalization. Further studies are warranted to identify reliable measures of the efficacy of regular blood transfusion therapy for the reduction of acute vaso-occlusive pain events.

Ineffective Erythropoiesis with Aging in Adults with Sickle Cell Disease

INTRODUCTION In the United States, life expectancy for adults with sickle cell disease (SCD) has improved over the last several decades and providers are now encountering increasing numbers of patients in the fourth, fifth and sixth decades. One notable feature of older SCD patients is lower ‘steady state’ hemoglobin (Hb) levels. Although it is well established that lower Hb levels are associated with increased adverse outcomes including pulmonary hypertension, stroke, cognitive decline, acute chest syndrome, frequency of vaso-occlusive crisis and shortened survival, a full understanding of the mechanisms accounting for the more prevalent and severe anemia in older SCD patients remains to be elucidated. Involved factors may include the long-term effect of chronic hemolysis, age-associated increased inflammation, progressive renal insufficiency and an age-related decline in nutritional adequacy. Despite lacking a uniform explanation for anemia applicable to individual SCD patients, it remains a management goal to optimize Hb level as possible within constraints associated with the development of secondary hemochromatosis. We postulate that the pathways to anemia in SCD patients may change with advancing age and that a better understanding of these pathways may result in a more directed intervention for the older sickle cell patient. METHODS Adult patients visiting Inova Adult Sickle Cell Center over a 6-month period (January through June 2023) with Hb levels below 9 g/dL were evaluated by a contemporary hematologic panel that included complete blood count with differential, reticulocyte count, comprehensive metabolic panel (included total bilirubin and creatinine), and lactate dehydrogenase (LDH). The reticulocyte proliferation index (RPI) was determined utilizing a readily accessible calculator (MedCalc) and a univariate regression analysis was performed for RPI against age. An RPI of &amp;lt; 2 was considered evidence for hypoproliferative anemia. RESULTS Of the 139 unique adult SCD patients visiting our clinic in this 6-month period, 60 had Hb levels equal to or below 9 g/dL. Of these, 8 patients had serum creatinine levels ≥ 1.5 mg/dL and were considered to have hypoproliferative anemia based on renal insufficiency. Among the remaining 52 patients, the mean age was 34.9 years, mean Hb was 7.49 g/dL and the mean RPI was 2.52. In patients with age ≤ 40 years, mean RPI was 2.74, compared to mean RPI of 1.61 in patients with age &amp;gt; 40 years. The mean Hb was 7.55 g/dL vs 7.21 g/dL mean total bilirubin was 3.08 mg/dL vs 2.15 mg/dL and mean LDH was 509 U/L vs 434 U/L in these two age groups (Fig 1). Regression analysis indicated that an increase in age corresponded to a reduction in RPI at 95% confidence level (Fig 2; regression coefficient: -0.04; 95% CI: -0.08 - -0.003; p-value: 0.03). CONCLUSION From the data we gathered, we conclude that despite chronic hemolysis in sickle cell disease, low RPI and ineffective erythropoiesis are evident to some extent in the majority of adult SCD patients even in the absence of renal failure and this significantly increases with age. Older patients with SCD are more likely to have ineffective erythropoiesis. We speculate that this may be evidence for age-associated bone marrow failure not unlike myelodysplasia (MDS) which occurs with increased frequency in the general population with advancing age. If future studies confirm disordered erythropoiesis, clonal hematopoiesis, or other markers of MDS, novel treatments known to be effective in patients with MDS may be examined in selected anemic SCD patients.

Real-World Treatment Outcomes of Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients Treated with Pegcetacoplan and Complement Protein 5 Inhibitors (C5i)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, potentially fatal disease characterized by complement-mediated hemolysis which clinically manifests with symptoms including fatigue, weakness and, in severe cases, thrombosis. Previous disease-modifying treatments solely comprised of complement protein 5 inhibitors (C5i) which effectively reduce intravascular hemolysis (IVH) in most patients with PNH. However, due to residual IVH and emerging extravascular hemolysis (EVH), complement protein 3 inhibitor (C3i), pegcetacoplan (PEG) has been recently approved to target the complement cascade further upstream, tackling both IVH and EVH. The aim of this study was to report real-world outcomes of PEG-treated and C5i-treated patients. Data were drawn from the Adelphi PNH Disease Specific Programme (DSP)™, a real-world, cross-sectional survey of physicians and their patients with PNH in France, Italy, Germany, Spain and the United States of America from January - November 2022. Patients were eligible for inclusion if they had received PEG for ≥1 month. Physicians recorded patient demographics, hemoglobin (Hb) levels, treatment administration and hospitalizations. The same patients were invited to self-report on symptomatology, fatigue via the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire, and impact on work and productivity via the Work Productivity and Activity Impairment (WPAI) questionnaire. Descriptive statistics were reported for patients receiving PEG from the DSP and from previously published data describing patients receiving C5i treatment (Panse, J et al. Eur J Haematol. 2022 Oct;109(4):351-363 1; Sicre de Fontbrune F et al. Hematology. 2022 Dec;27(1):1140-1151 2). Fourteen physicians reported data for 61 patients receiving PEG. Mean (standard deviation; SD) age was 37.1 (11.3) years and 59.0% of patients were male. Mean (SD) time since diagnosis was 3.7 (3.3) years and mean (SD) time receiving PEG was 5.9 (4.0) months. All patients received 1080 mg dose of PEG, with 98.3% of patients receiving this dose twice weekly. For PEG-treated patients mean (SD) Hb from the most recent result was 11.5 (1.6) g/dL and 34.4% of patients had Hb &amp;gt;12 g/dL. Published literature based on a real-world survey reported C5i-treated patients had a mean (SD) Hb of 10.2 (2.0) g/dL and 14.3% had Hb &amp;gt;12 g/dL 1. C5i-treated patients had mean (SD), 0.4 (1.0) emergency room (ER) visits during the 12-months prior to data collection 2. In the DSP sample, no patients required ER visits during the time they were receiving PEG. Thirty PEG-treated patients provided self-reported data with less reporting to experience shortness of breath (23.3% vs 46.5%), difficulty swallowing (10.0% vs 19.7%) and abdominal pain (16.7% vs 19.7%) at the time of survey than C5i-treated patients 1. At the time of survey 83.3% of PEG-treated patients reported fatigue (63.4% C5i patients in the literature 1). PEG-treated patients reported a mean (SD) FACIT-F score of 37.4 (8.6). C5i-treated patients reported 35.0 (13.7) 1. 73.5% of PEG-treated patients were employed, 2.5% reported absenteeism and 22.4% reported overall activity impairment. For previous literature regarding C5i patients this was 57.7%, 10.2% and 37.5%, respectively 1. We assessed previously published literature of C5i-treated patients and demonstrated favorable outcomes for PEG-treated patients across the endpoints assessed in this analysis. Patients receiving PEG reported higher Hb and FACIT-Fatigue scores than C5i-treated patients. More PEG-treated patients remained in paid employment and reported less impact on their daily activities than C5i-treated patients. Further research is required to explore the real-world effectiveness of PEG compared to other therapeutic options and understand how newer therapies can improve outcomes for patients with PNH.

Efficacy of Low Dose Vs Standard Dose of Thalidomide in Patients with Transfusion-Dependent Thalassemia (TDT): A Non-Inferiority Trial

Background Thalidomide has been demonstrated to induce global gene expression hereby increasing the proliferation of erythroid cells. Recent studies have revealed encouraging data regarding the efficacy and safety of thalidomide in both transfusion dependent (TDT) and non-transfusion dependent (NTDT) thalassemia. However, the optimal dose of thalidomide remains unclear. The study was designed to compare the efficacy and safety of thalidomide at low-dose (1 mg/kg/d) vs standard-dose (2 mg/kg/d). Methods Patients with TDT &amp;gt; 12 years of age with no recent (previous 6 months) intake of Hb enhancers were enrolled in a non-inferiority trial across 4 sites in India. Patients with hypersplenism, prior history of thromboembolism, HIV, active hepatitis B/C infection, or any other known systemic illness like neurological, renal, significant hepatopathy, and sexually-active females unwilling to use contraceptives/undergo medical termination of pregnancy in case of accidental pregnancy while on the drug were excluded. Patients were randomised to receive low-dose or standard-dose thalidomide for 6 months. Pre-transfusion Hb, transfusion frequency and volumes, and adverse effects were recorded at each visit. Response was graded based on reduction in transfusion requirement at 24 weeks: Good (&amp;gt; 50 %), moderate (25-50 %), or minimal (&amp;lt;25%). Results: A total of 188 patients with mean age of 18.1 ± 5.2 years and M:F ratio of 2.1:1 were enrolled. 85.6% (80 in low-dose and 81 in standard-dose) participants completed the study period. 14.4% discontinued thalidomide due to various reasons. The mean Hb and baseline transfusion requirement were 8.6 ± 0.98 g/dl and 35.91 ml/kg in the preceding 12 weeks. The overall response rate was 55.9%. There was no statistically significant difference in the response rates in 2 groups (63% in low-dose vs 48% in standard-dose) (p:0.135). Good, moderate, and minimal responses were seen in 19.3%, 36.6 %, and 44.1% of the participants respectively. Response rate was not affected by age, sex, transfusion requirement or serum ferritin at baseline. The commonest adverse events were somnolence (n=40), constipation (n=29), weight gain (n=25), reversible cytopenia's (n=22), and peripheral neuropathy (n=14). 3.7% participants experienced Grade 2/3 events. There were no grade 4 events. Conclusions: The low-dose thalidomide was as efficacious as the standard dose in reducing transfusion requirements. Thalidomide is well tolerated and can be considered as an adjunct to optimal transfusion-chelation regimen under close monitoring in a resource constrained setting.

Fetal Hemoglobin Decrease during Voxelotor Treatment

Sickle cell disease (SCD) is an inherited disorder caused by a point mutation in the β-globin gene leading to the formation of hemoglobin S (HbS). The polymerization of deoxygenated HbS is the first event in the molecular pathogenesis of SCD resulting in sickling of red blood cells (RBC), and hemolytic anemia which has been shown to be associated with organ damage and early death. Hemolytic anemia is defined by an accelerated rate of destruction RBC resulting in a lowered Hb level and a reduced gas transport capacity. Because Hb S in its oxy (R) conformation do not polymerize, drugs modifying hemoglobin (Hb) to increase the proportion of oxy-HbS have been propose to inhibit HbS polymerization. Voxelotor is such a molecule, which allosterically modifies Hb-oxygen affinity improving anemia and reducing hemolysis. However, the impact of Voxelotor on HbF levels is unknown. We describe here variations of %HbF and Mean corpuscular HbF (MCHbF) in a cohort of homozygous SCD patients treated with Voxelotor in our Sickle Cell Referral center. We conducted a prospective register study to analyze clinical and biological evolution of SCD patients treated with Voxelotor at 1500mg taken orally once daily. From December 2021 through December 2022, 25 SCD adult patients were followed during a median of 7 months [1-12]. Among them, HbF values were analyzable for 15 patients (SS gentype n=14; women in 73%; median age of 50 years [24-61]) who completed 6 months of Voxelotor with no transfusion during the same period; and with a stable dose of hydroxyurea (HU), for at least 3 months before inclusion and during the study in case of patients treated by HU (n=10). The dose of Voxelotor was stable for 13/15 patients and was decreased in 2 patients due to skin allergy (n=1) and moderate digestive intolerance. One patient died after 6 months of treatment in a context of end-stage renal failure and severe pulmonary hypertension not related to Voxelotor treatment. Mean corpuscular HbF (MCHbF) was calculated (MCHbF (pg) = MCH x %HbF). HbF percentage was measured by high performance liquid chromatography (Biorad, Variant II, beta-thal dual program). All participants provided written informed consent (CPP Erythropedie). From baseline to 6 months of follow up mean Hb (g/dL) concentration increased from 7.4 [5.4-8.5] to 8 [5-11.9] (p=0,0003; Figure A); absolute reticulocyte count (ARC ; Giga/L) decreased from 158 to 145 (p=0,005), %HbF decreased by 63% in all patients from 7,1% to 3,3% (p=0,008; Figure B) and MCHbF (pg) decreased from 3,36 to 1,03 (p=0,001; Figure D). A decrease in % HbF was observed from the first 15 days of treatment in both groups of patients treated or not with HU (Figure C) ; no changes in mean corpuscular volume (p=0.15) was observed in patients treated with HU during follow up. The HbF decrease in SCD patients treated with Voxelotor could be explained by different mechanisms: - Reduction of stress erythropoiesis which is due to an increase in erythroid output in response to anemic stress associated with a reduced expression of BCL11A, a transcriptional repressor that inhibits adult-stage HbF expression. This hypothesis is supported by the reduction in reticulocytes in patients treated with Voxelotor - The loss of an HbF-related survival advantage for SCD RBCs, while the normal RBC lifespan is approximatively 120 days, in SCD RBCs it is only a sixth of it. HbF is a major modulator of SCD and prolonge SCD RBCs survival. Its protective effect relies on its quantity and distribution among the RBC population, which is often heterogeneous in SCD patients. Protection against polymerisation of Voxelotor is probably more homogeneous among RBCs. As a result, RBCs containing low levels of HbF, which would normally disappear, have a prolonged lifespan. Similarly, it was presumed that sickling of erythroblasts could lead to ineffective terminal erythroid differentiation with an anti-apoptotic role for HbF during the terminal stages of erythroid differentiation. However we found no significant difference for index of ineffective erythropoiesis (soluble transferrin receptor / absolute reticulocyte count) before and after 6 months of treatment. The question raised is therefore that of the risk of a rebound effect upon discontinuation of Voxelotor, which has a short half-life, during the time it takes for HbF to increase. To better study this hypothesis, distribution of HbF/RBC will be studied in the HEMOPROVE trial (NCT05199766) currently in progress.