Rise In Hb Research Articles

Efficacy of imetelstat on red blood cell (RBC)-transfusion independence (TI) in the absence of platelet transfusions or myeloid growth factors in IMerge.

6566 Background: In the IMerge trial (NCT02598661) of RBC transfusion-dependent (TD) patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) relapsed/refractory to or ineligible for erythropoiesis stimulating agents, imetelstat showed significant efficacy vs placebo (PBO) for 8-wk, 24-wk, and 1-y TI endpoints, with neutropenia and thrombocytopenia as the most common adverse events (Platzbecker. Lancet 2024). Supportive care was given to all pts as needed, per investigator discretion. Here we report RBC-TI rates in the absence of platelet transfusions or myeloid growth factor use. Separately, RBC-TI with mean central hemoglobin (Hb) rise of ≥1.5 g/d was assessed in all pts. Methods: Pts were randomized 2:1 to receive imetelstat (n=118) 7.5 mg/kg or PBO (n=60) Q4W IV until disease progression. Primary endpoint was 8-wk RBC-TI; 24-wk RBC-TI was a key secondary endpoint. Primary analysis cutoff was Oct 2022, with Oct 2023 cutoff for 1-y RBC-TI analyses. Results: Overall, 21/118 (18%) pts in the imetelstat group and 1/60 (2%) pts in the PBO group needed platelet transfusions; 41/118 (35%) and 2/60 (3%) pts received myeloid growth factors, respectively. Significantly higher percentages of pts achieved 8-wk, 24-wk, and 1-y RBC-TI with imetelstat vs PBO in the absence of either platelet transfusions or growth factor support (Table). In a separate analysis, 8-wk, 24-wk, and 1-y RBC-TI and concurrent Hb rise of ≥1.5 g/dL with imetelstat vs PBO occurred in 28% vs 2%, 23% vs 0%, and 17% vs 0% of pts, respectively (Table). Among responders, imetelstat increased median central Hb levels compared with PBO: 3.6 g/dL vs 0.8 g/dL for 8-wk, 4.2 g/dL vs 1.1 g/dL for 24-wk, and 5.2 g/dL vs 1.7 g/dL for 1-y RBC-TI. Conclusions: Results from this subanalysis confirm that pts who achieve RBC-TI with imetelstat do so without developing severe neutropenia and thrombocytopenia (functionally defined as needing myeloid growth factors or platelet transfusions, respectively), therefore not negating the clinical benefit of the drug. Imetelstat also led to significant rise in Hb levels in RBC-TI responders, particularly long-term responders. These data further support the efficacy of imetelstat in TD pts with LR-MDS. Clinical trial information: NCT02598661 . [Table: see text]

#1614 Fenofibrates and chronic kidney disease – Is there anything to worry about?

Abstract Background and Aims Chronic Kidney Disease (CKD) patients have increased risk of cardiovascular disease and dyslipidemia is a frequent comorbidity. Many patients are medicated with anti-lipidemic agents to reduce atherosclerotic disease and coronary vascular events. Fenofibrates are lipid-lowering agents used to treat mixed dyslipidemia and hypertriglyceridemia and are widely used by primary care physicians. Many studies described reversible increase in serum creatinine (SCr) associated with fenofibrates use, but the underlying mechanism is poorly understood. Whether hypercreatinemia is secondary to alterations in creatinine metabolism, tubular handling, or reflects a true impairment in kidney function remains unknown. This phenomenon is also fairly unknown to many primary care providers and, as a result, patients with a SCr rise while on fenofibrates are often referred to nephrology consultation. In this study, we have analyzed the effect of fenofibrate withdrawal on SCr, eGFR and hemoglobin (Hb) in patients referred to nephrology consultation for CKD or decrease of eGFR. Our aim was to understand the impact of fenofibrates withdrawal on kidney function and to look for factors that might influence the risk of fenofibrate nephrotoxicity. Methods We conducted a retrospective observational study, reviewed electronic medical records and collected data of all adult patients discontinued on fenofibrates at first nephrology consultation, between January 2022 and October 2023. Ninety patients were included, of which four were excluded due to simultaneous suspension of antihypertensive drugs. Patients were subsequently evaluated for clinical reasons from 2 to 6 months after the first appointment, with new laboratory data collected, including Hb, SCr and lipid profile. eGFR was calculated using MDRD 4 formula. Continuous variables were compared by t-test and categorical variables were compared by chi-square test. A p value of < 0.05 was considered statistically significant. All data was analyzed using Stata software. Results A total of eighty-six patients were included in this study, 65% (n=56) were male, mean age of 71.2 ± 11.4 years old; all patients were medicated with fenofibrates due to dyslipidemia and 77% (n=66) were also on statins; 94% (n=81) had hypertension, 60% (n=52) had type 2 diabetes mellitus, and 20% (n=17) had ischemic cardiopathy. Ninety-two percent (n=79) were taking renin-angiotensin system inhibitors (RASi). Nearly half the patients (49% n = 42) had stage 4 CKD and 45% (n = 39) had stage 3 CKD; Main causes of CKD were presumed diabetic kidney disease (34% n = 29) and ischemic nephropathy (15% n = 13), 30% (n = 26) of patients had undetermined etiology. Upon fibrate discontinuation, mean SCr was 2.1 ± 0.6 mg/dL and mean eGFR was 31.3 ± 10.9 mL/min/1.73 m2. Mean Hb was 12.5 ± 2.0 g/dL. After fenofibrate discontinuation, eGFR significantly improved in mean 15.2 mL/min/1.73 m2 (31.3 vs 46.5 mL/min/1.73 m2, p < 0.0001) with a mean reduction of SCr of 0.6 mg/dL (2.1 vs 1.5 mg/dL, p < 0.0001). Mean Hb increased 0.4 g/dL (12.4 vs 12.7 g/dL, p = 0.112). Mean total cholesterol was 168.4 ± 56.4 mg/dL and mean triglycerides was 234.8 ± 285.3 mg/dL. Only one patient was restarted on fenofibrate due to severe hypertriglyceridemia. Fenofibrate discontinuation effect on eGFR improvement remained statistically significant when adjusted for diabetes, hypertension, CKD etiology and RASi use. Conclusion Our study reports a consistent increase in eGFR and SCr decrease following discontinuation of fenofibrate, as other reports before. A true effect on eGFR could be supported by the Hb rise, though it did not reach statistical significance. The exact mechanism by which fenofibrates increase SCr remains to be clarified. Cardiovascular disease is the main cause of death amongst CKD population and the potential benefits of fenofibrates should not be disregarded. Our results suggest that patients started on fenofibrates should be carefully selected, specially if CKD is present, and kidney function monitoring should be considered. A drop in eGFR should prompt physicians to weigh on the strict indications for fenofibrates use.

A comparative study of ferric carboxymaltose and iron sucrose as a parenteral iron treatment in iron deficiency anemia during pregnancy in a tertiary care hospital

Background: Anemia from the Greek word (anhaima) meaning “without blood” is the deficiency of red blood cell and/or hemoglobin which result in reduced oxygen-carrying capacity of blood causing tissue hypoxia. Aims and Objectives: To study the efficacy and safety of intravenous ferric carboxymaltose (FCM) versus iron sucrose in the management of iron deficiency anemia in pregnancy. Materials and Methods: A prospective, single-center, comparative interventional randomized study was carried among 180 antenatal mother admitted to antenatal ward in the Department of Obstetrics and Gynaecology of Burdwan Medical College and Hospital, from July 1st, 2020, to December 30th, 2021. Results: A total of 180 patients, 90 patients in each FCM and iron sucrose group, were included in the study. There was significant (P=0.001) mean change in hemoglobin (Hb) level in both the groups from pre-treatment to 3 and 6-week post-treatment. There was also a significant (P=0.001) mean change in ferritin level in both the groups from pre-treatment to 3 and 6-week post-treatment. The mean change in Hb level and ferritin level was higher among patients of FCM compared to iron sucrose. The adverse reactions were lower among patients of FCM than iron sucrose. Conclusions: This study found that FCM is safer than iron sucrose. Treatment with FCM resulted in rapid replenishment of iron stores in pregnant women with significantly high rise of Hb and ferritin levels over a 6-week period with lesser adverse effects.

Pengaruh Pemberian Jus Buah Bit dengan Kenaikan HB Remaja Putri di SMK Guna Dharma Kota Bandar Lampung

ABSTRACT English translation. Iron nutrition anemia can cause a decrease in physical ability, work productivity, and thinking ability. SMK GUNA DHARMA Bandar Lampung City found the highest population of adolescent girls with anemia as many as 92 adolescent girls and 30 adolescent girls of whom had anemia (31.5%) based on the results of laboratory checks and characteristics during physical examination. In addition, based on the results of interviews, young women said they never took drugs or foods that could help increase blood regularly. The purpose of this study is to determine the effect of giving beet juice with an increase in Hb for young women at SMK Guna Dharma Bandar Lampung City in 2023. Type of quantitative research. Pre-experimental research design with one group pretest – posttest design approach. The population of grade 1 and 2 girls at SMK Guna Dharma Bandar Lampung City with a total of 92 people in 2023. Purposive sampling technique. Data analysis using univariate and bivariate using Wilcoxon test. An influence of giving beet juice with an increase in Hb for young women at SMK Guna Dharma Bandar Lampung City in 2023.The average Hb in adolescent girls before being given beetroot juice with a Mean of 10.470gr / dl which means adolescent girls have mild anemia. The average Hb in adolescent girls after being given beetroot juice with a mean of 11.117gr / dl which means adolescent girls are no longer anemic / normal. The results of the statistical test obtained a mean difference test of 1.06 P-value = 0.000 (<0.05) which means that there is an influence of giving beet juice with an increase in Hb for young women at SMK Guna Dharma Bandar Lampung City in 2023. English translation. it is expected for young women to always consume beet juice, and consumption of foods that contain lots of iron is highly recommended in adolescents who have anemia, because it will help the process of increasing Hb. Keywords:English translation. Beetroot Juice, HB Rise, Young WomenEnglish translation.

Long-Term Safety and Efficacy of Mitapivat, an Oral Pyruvate Kinase Activator, in Adults with Sickle Cell Disease: Extension of a Phase 1 Dose Escalation Study

BACKGROUND In a Phase I study (NCT04000165, Xu et al, 2022), we showed that mitapivat, an investigational oral allosteric activator of pyruvate kinase (PK), demonstrated an acceptable safety and tolerability profile at multiple ascending dose levels in patients (pts) with sickle cell disease (SCD). We also established proof-of-concept for activating PK as a viable therapeutic approach; mitapivat decreased 2,3- diphosphoglycerate (2,3-DPG) and increased adenosine triphosphate (ATP) levels, improved hematologic parameters, and reduced sickling in pts with SCD (HbSS). In this extension study (NCT04610866), we evaluated the safety, tolerability and efficacy of mitapivat as a long-term maintenance therapy for pts with SCD. METHODS We enrolled 15 adult pts (age >18 years) with confirmed SCD (HbSS) and baseline hemoglobin (Hb) 7.1 - 10.5 g/dL, with no recent blood transfusions, erythropoietin therapy, or changes in SCD-specific therapies including hydroxyurea (HU) and L-glutamine. Thirteen pts had participated in the Phase 1 study and 2 pts were mitapivat naïve. All pts started mitapivat at 50 mg twice daily (BID), escalating after 4 weeks (wks) to 100 mg BID, unless a rapid Hb rise was observed (increase of ≥2 g/dL), the maximum Hb level of 12.5 g/dL had been reached, or per PI discretion. Patients continued on this maintenance dose of mitapivat through the end of the study. Dose reductions were performed at any time during the extension phase for safety and tolerability. After completion of the 24-wk core period, pts had an option to continue on mitapivat treatment in the extension period for up to 6 years. Study visits were conducted every 2 wks (x2), 4 wks (x2), and then every 12 wks for first 2 years (yrs) and will continue every 6 months for the remaining 4 yrs. The extension period of the study is ongoing; here we report data for up to 2 years (data cutoff March 23, 2023). Any and all vaso-occlusive crises (VOCs) that occurred while on study, regardless of attribution, were considered adverse events. RESULTS Of the 15 pts who completed the core period, 14 entered the extension study with 1 pt on 5 mg BID, 1 pt on 50 mg BID, 3 alternating between 50 and 100 mg BID, and the rest on 100 mg BID. Mean age of the 15 pts was 39 yrs (range: 25-57 yrs); 10 were male, and 11 were on HU. As of the cut-off date, median duration of mitapivat treatment for pts who entered the extension period was 84 wks (range: 48-108 wks), 1 pt discontinued after 2 yrs (pt decision) and 10 pts received 72 wks or more of treatment (Table 1) with a total of 1080 pt-wks of drug exposure thus far. Mitapivat was generally well tolerated; no treatment emergent adverse events (TEAEs) resulted in discontinuation of study drug or death during the extension period. The most common TEAEs (reported in 5 or more pts) were VOCs (n=8), estrone decrease (n=7), testosterone increase (n=6) and cough (n = 5); changes in laboratory values were not clinically significant. The most common serious TEAEs (reported in 2 or more pts) were VOCs (n=8) and lung infection (n = 2). Two pts experienced VOCs that were assessed as possibly drug-related (1 during drug escalation, and 1 during drug taper). All VOCs occurred in the setting of known VOC triggers. Three pts required dose reduction, 1 each secondary to pruritis, bloating and insomnia, respectively. In the latter 2 cases, the doses were subsequently increased to 100 mg BID, as TEAEs resolved. Other serious TEAEs were not considered related to study drug. The mean Hb at 24 wks increased significantly from baseline (mean: 1.38 g/dL, SD: 0.88 g/dL; p<0.0001), a result generally upheld at other follow-up periods (Fig. 1). 14/15 (93%) of the pts achieved a Hb response, defined as a ≥ 1 g/dL increase in Hb at any timepoint within the core period, compared to baseline. Improvements in Hb achieved in the core period were accompanied by improvements in markers of hemolysis, oxygen affinity (p50), sickling kinetics (t50), decreases in 2,3-DPG and increases in ATP levels, and were sustained in the extension study (Fig. 1 and 2). Concurrently, there were also improvements in red cell deformability (LORRCA) (Lundt et al, 2022) and trends in improvements in cardiopulmonary status (not shown). CONCLUSION Long-term use of mitapivat is safe and well tolerated in pts with SCD with evidence of sustained long-term improvements in Hb, hemolytic and sickling kinetics. Mitapivat offers a novel disease-modifying approach.

Factors Governing the Erythropoietic Response to Intravenous Iron Infusion in Patients with Chronic Kidney Disease: A Retrospective Cohort Study.

Limited knowledge exists about factors affecting parenteral iron response. A study was conducted to determine the factors influencing the erythropoietic response to parenteral iron in iron-deficient anaemic patients whose kidney function ranged from normal through all stages of chronic kidney disease (CKD) severity. This retrospective cohort study included parenteral iron recipients who did not receive erythropoiesis-stimulating agents (ESA) between 2017 and 2019. The study cohort was derived from two groups of patients: those managed by the CKD team and patients being optimised for surgery in the pre-operative clinic. Patients were categorized based on their kidney function: Patients with normal kidney function [estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2] were compared to those with CKD stages 3-5 (eGFR < 60 mL/min/1.73 m2). Patients were further stratified by the type of iron deficiency [absolute iron deficiency (AID) versus functional iron deficiency (FID)]. The key outcome was change in hemoglobin (∆Hb) between pre- and post-infusion haemoglobin (Hb) values. Parenteral iron response was assessed using propensity-score matching and multivariate linear regression. The impact of kidney impairment versus the nature of iron deficiency (AID vs. FID) in response was explored. 732 subjects (mean age 66 ± 17 years, 56% females and 87% White) were evaluated. No significant differences were observed in the time to repeat Hb among CKD stages and FID/AID patients. The Hb rise was significantly lower with lower kidney function (non-CKD and CKD1-2; 13 g/L, CKD3-5; 7 g/L; p < 0.001). When groups with different degrees of renal impairment were propensity-score matched according to whether iron deficiency was due to AID or FID, the level of CKD was found not to be relevant to Hb responses [unmatched (∆Hb) 12.1 vs. 8.7 g/L; matched (∆Hb) 12.4 vs. 12.1 g/L in non-CKD and CKD1-2 versus CKD3-5, respectively]. However, a comparison of patients with AID and FID, while controlling for the degree of CKD, indicated that patients with FID exhibited a diminished Hb response regardless of their level of kidney impairment. The nature of iron deficiency rather than the severity of CKD has a stronger impact on Hb response to intravenous iron with an attenuated response seen in functional iron deficiency irrespective of the degree of renal impairment.

Sucrosomial® iron effectiveness in recovering from mild and moderate iron-deficiency anemia in the postpartum period

BackgroundPostpartum iron deficiency anemia (PPIDA) is highly prevalent in developing countries where it constitutes an important cause of maternal morbidity and mortality. Potential determinants of PPIDA are prepartum iron deficiency or iron deficiency anemia in association with severe blood loss during delivery. We investigated the efficacy of oral Sucrosomial® iron for recover from mild-to-moderate PPIDA.MethodsThis pilot study was conducted in three medical centers in Romania.Adult women (≥ 18y) with mild (hemoglobin [Hb] 9–11 g/dL) or moderate (Hb 7–9 g/dL) PPIDA diagnosed at screening (2–24 h after delivery) were eligible.Women with mild PPIDA received oral Sucrosomial® iron (Pharmanutra, S.p.A, Italy) once daily (30 mg elemental iron per capsule) for 60 days. Those with moderate PPIDA received oral Sucrosomial® iron twice daily (60 mg elemental iron) for 10 days, followed by a 50-day course of oral Sucrosomial® iron once daily (30 mg elemental iron). Laboratory parameters, as well as subjective clinical symptoms using a 3-point Likert Scale, were assessed at baseline and on study days 10, 30 and 60.ResultsSixty anemic women entered the study, but three were missed during follow-up. At day 60, a Hb rise was observed in both groups (+ 3.6 ± 1.5 g/dL; p < 0.01), 81% experienced correction of anemia (Hb ≥ 12 g/dL), 36% achieved a ferritin concentration ≥ 30 ng/mL (p < 0.05), and 54% a transferrin saturation (TSAT) ≥ 20% (p < 0.01). For women still anemic at day 60, mean Hb was close to normality (11.3 ± 0.8 g/dL). Resolution of IDA-associated clinical symptoms was already observed just 10 days after treatment initiation. No patient discontinued treatment due to gastrointestinal adverse events.ConclusionsSucrosomial® iron was shown to be potentially effective and well tolerated at treating mild and moderate PPIDA. These results encourage the use of oral Sucrosomial® iron as a treatment option for PPIDA, but larger studies with longer follow-up are warrant.

Hemoglobin Change after Red Blood Cell Transfusion for Postpartum Anemia: Secondary Analysis of a Randomized, Controlled Trial.

We aimed to describe hemoglobin (Hb) change after transfusion in the nonacute postpartum anemic population in order to provide clinicians with appropriate expectations regarding Hb rise posttransfusion. We performed a secondary analysis of a randomized controlled trial comparing initial transfusion with 1 unit of packed red blood cells (pRBCs) to 2 units pRBCs for postpartum women requiring nonacute transfusion (n = 66). Inclusion criteria were: age 18 years and older, Hb level either <7 g/dL or >7 g/dL with signs or symptoms of anemia, and > 6 hours postpartum without contraindication to transfusion. Hb assessment was performed 4 to 6 hours after initial transfusion. Hb change (ΔHb) was calculated as posttransfusion Hb minus randomization Hb. Our primary goal was to describe mean ΔHb per pRBC transfused at the 4- to 6-hour posttransfusion blood count. We also compared ΔHb per pRBC transfused by number of units transfused, body mass index (BMI), and symptoms (dizziness and/or fatigue) at time of posttransfusion assessment. Participants were mean age 29, mean BMI of 27, and over 70% self-identified as black, 12% identified as white, and 9% as Asian race. Mean Hb prior to transfusion was 6.9 ± 0.6 g/dL. Mean ΔHb per pRBC transfused was 0.9 ± 0.4g/dL. There was no difference in ΔHb per pRBC by BMI category (normal weight < 25 kg/m2: 1.1 ± 0.2 g/dL; overweight 25-29.9 kg/m2: 0.9 ± 0.5 g/dL; obese ≥ 30 kg/m2: 0.9 ± 0.5 g/dL; p = 0.12). Finally, there was also no significant difference in ΔHb per pRBC by whether or not symptoms of anemia persisted after initial transfusion (1.0 ± 0.7 vs. 0.9 ± 0.4 g/dL, p = 0.39). Our data supports the classically accepted rise in Hb after pRBC of approximately 1 g/dL, regardless of BMI category or anemia symptomatology. The study population includes patients at highest risk of postpartum anemia. The results of our study provide important information for clinicians caring for postpartum patients with nonacute anemia. · Postpartum anemia is a significant public health issue.. · Providers use hemoglobin change to assess response to blood transfusion.. · The established 1 g/dL change in Hb after transfusion is based on historic surgical populations.. · Our data suggests the 1 g/dL Hb change is applicable to postpartum patients..

Randomized Controlled Trial Comparing Ferrous Sulfate and Iron Sucrose in Iron Deficiency Anemia in Pregnancy.

Anemia among pregnant women is one of the major health concerns for healthcare workers. The management becomes a concern in the pregnancy where the question arises of which is better the intravenous iron sucrose or the oral ferrous sulfate tablets. To answer this, a randomized control trial comparing both the treatment options in a tertiary care government hospital was set up in the hilly terrains of India. This study discusses the effectiveness and practical aspect of using both, which seems to be the better out of both, and why. The study was conducted as a parallel-group, open-label randomized controlled trial (RCT) in the Department of Obstetrics and Gynecology of a tertiary care government hospital in India, with approximately 4,000 delivery loads annually. Ethical clearance was obtained from the institute's ethics committee (IEC), and the trial was registered with the Clinical Trial Registry of India (REF/2022/06/055013). Two hundredsixty-eight pregnant women between 18 and 45 years of age with moderate iron deficiency anemia (IDA) (hemoglobin (Hb) 7-9g/dl, microcytic-hypochromic, and serum ferritin <30ng/ml) were included in the study. Patients were randomly divided into two groups: group 1 with 134 patients to receive intravenous iron sucrose and group 2 with 134 patients to receive oral ferrous sulfate tablets. The intravenous iron sucrose is superior in terms of tolerability and correction of iron deficiency anemia during pregnancy. It yields a quicker rise in Hb and serum ferritin with no major side effects. In the difficult terrain of Himachal Pradesh, this makes IV iron sucrose a better option for anemic pregnant women who do not have easy access to health facilities resulting in a large number of them reaching hospitals with moderate to severe anemia at a later gestation.

Lower starting dose of roxadustat in non-dialysis-dependent chronic kidney disease patients with anaemia: a study protocol for a randomised, multicentre, open-label study

IntroductionRoxadustat is a first-in-class oral therapy that treats chronic kidney disease (CKD) anaemia with the benefit of a novel mechanism of action that consistently corrects and maintains haemoglobin (Hb) across...

Lactoferrin: A Promising New Player in Treatment of Iron Deficiency Anemia in Patients on Regular Hemodialysis: A Randomized Controlled Trial.

Hepcidin is secreted in inflammatory states as in patients on regular hemodialysis (HD). Therefore, novel agents modulating hepcidin secretion may have the potential to effectively reverse anemia in HD patients. Bovine milk derivative lactoferrin (BLF) is a glycoprotein that was found to decrease serum interleukin-6, therefore, having anti-inflammatory properties. Thus, it can downregulate hepcidin secretion in various inflammatory states including patients on regular HD, so improving iron absorption and utilization in those patients. In addition, BLF is a source of iron as each BLF molecule chelates two ferric ions. We started an interventional study. Seventy patients on regular HD with iron deficiency anemia received 100 mg of 20%-30% iron-saturated BLF (corresponding to 70-84 μg of elemental iron) orally b.i.d for 6 months. We compared those patients with another 70 patients on regular HD with iron deficiency anemia who were given 576 mg of ferrous glycine sulfate (corresponding to 100 mg of elemental iron) orally b.i.d for 6 months. BLF significantly decreased serum hepcidin level (from 340-350 ng/mL to 101-112 ng/mL), P <0.0001 and significantly increased hemoglobin (Hb) concentration (from 7.5-8.1 g/dL to 9.3-10 g/dL), P <0.0001, and transferrin saturation (TSAT) (from 5%-9% to 26%-31%), P <0.0001. Furthermore, ferrous glycine sulfate significantly decreased serum hepcidin level (from 335-350 ng/mL to 330--341 ng/mL), P <0.0001, and significantly increased Hb (from 7.5-8.1 to 7.6-8.5 g/dL), P <0.0001, and TSAT (from 5%-9% to 7%-12%), P <0.0001. However, the magnitude of decrease in serum hepcidin level and rise in Hb and TSAT in the BLF group was significantly higher than in the ferrous glycine sulfate group, P <0.0001. Oral BLF can be considered a promising novel agent in treatment of iron deficiency anemia in patients on regular HD.

GBT021601 Increases Hemoglobin and Improves Red Blood Cell Deformability without Rebound Hyperviscosity upon Drug Clearance in a Sickle Mouse Model

Background: Whole-blood viscosity and red cell deformability are markedly abnormal in sickle cell disease (SCD) due to sickling of red blood cells (RBCs). Increased whole-blood viscosity is a risk factor for vaso-occlusive crisis (VOC), avascular necrosis, and proliferative retinopathy. Blood viscosity is strongly impacted by hemoglobin (Hb) levels and RBC deformability. GBT021601 is a potent next-generation sickle hemoglobin (HbS) polymerization inhibitor, with anti-sickling properties, that increases the oxygen affinity of Hb. In preclinical studies, treatment with GBT021601 achieved higher levels of Hb than the US Food and Drug Administration-approved first-generation compound voxelotor, raising concern that this rise in Hb would substantially increase whole-blood viscosity and impose a VOC risk after treatment cessation. Objective: To investigate a potential rebound hyperviscosity effect from GBT021601 cessation in a murine model of SCD by determining the effect on whole-blood viscosity and on RBC deformability under a range of oxygen concentrations using oxygen gradient ektacytometry. Methods: Nine-week-old Townes HbSS mice were fed chows containing 0.2% GBT021601 for 5 weeks, then transitioned to control chow. Whole blood was collected in an EDTA tube. All tests were conducted within 4 hours of collection. Using an Element HT5 hematology analyzer (Heska), complete blood count was obtained from mice while on GBT021601 (day 0) and then on days 1, 3, and 5 after transition to control chow. Blood viscosity was measured with a cone/plate viscometer (AMETEK Brookfield) at 37 °C at shear rates of 45 s-1 and 225 s-1. Hematocrit to viscosity ratio (HVR) was calculated to determine RBC oxygen-carrying capacity. RBC deformability was measured by oxygen gradient ektacytometry (Lorrca, RR Mechatronics). Results: Treatment with GBT021601 significantly increased Hb from 8.0 to 12.9 g/dL (P<0.0001) without increasing HVR. Compared with previous studies with the voxelotor analog GBT1118, Hb dropped off more slowly with GBT021601 treatment; this allowed for the ideal assessment of whole-blood viscosity and HVR when the drug had cleared, and HbS was no longer modified, despite elevated Hb levels. HVR at both 45 s-1 and 225 s-1 showed no significant change with drug clearance. GBT021601 treatment also improved RBC deformability, as indicated by a higher elongation index (EI) under both normoxic (EImax, P<0.001) and hypoxic (EImin, P<0.0001) conditions. Point of sickling (PoS) was also reduced (P<0.0001), indicating that treated RBCs tolerated lower oxygen concentrations before sickling. When the drug was withdrawn, PoS and EImin returned to baseline levels, whereas EImax remained elevated until day 5 off treatment. Hb also remained elevated until day 5 off treatment, despite the return to baseline levels of the EImin, PoS, and p50 (partial oxygen pressure at which Hb is 50% saturated with oxygen), indicating drug clearance. Conclusions: In response to GBT021601, sickle cell mice showed a robust increase in Hb, comparable to that of a HbAS mouse, as well as a marked improvement in PoS and RBC deformability. When normalized to HVR, there was no significant difference in blood viscosity during treatment and after cessation of treatment. This finding suggests that oxygen-carrying capacity is not impaired and provides no indication for rebound hyperviscosity with drug clearance. Moreover, the observation that EImax remained elevated until 5 days after drug cessation suggests that some residual rheological improvement occurred in the RBC population that did not dissipate when the drug was cleared. In vitro addition of GBT021601 (and other related compounds) to blood rapidly increases the EImin and reduces the PoS of RBCs but does not alter the EImax. In contrast, an increase in the EImax of RBCs has been consistently observed with GBT021601 treatment in vivo, including in early clinical studies in patients with SCD. The precise mechanism by which this benefit is obtained requires further study. Funding: Global Blood Therapeutics.

Application of Rhuepo to Post-Chemotherapy Blood Cancer Patients and Clinical Observation

Aim: Clinical use of Recombinant Human Erythropoietin (rHuEPO) effectively increases the level of Hemoglobin in blood and improve quality of life of patients. Methods: Blood cancer patients is divided into two groups namely Treatment group and Control group. There is altogether 24 patients in treatment gp to whom both chemotherapy and rHuEPO is given for 4 weeks. rHuEPO is given as 150u/kg，subcutaneously, three times a week. Blood routine check up is done in every week and iron is prescribed after 2 weeks. Result: After 4 weeks of treatment, patients were evaluated for drugs effectiveness in both groups; total effectiveness were 58.34% and 20% respectively, P &gt;0.05; after 4 weeks of treatment, there was distinct statistical significance. Comparing with pretreatment level, Treatment group has remarkable rise in Hb after 4 weeks (81.29±9.85)对（65.75±12.37），（P&lt;0.01, whereas control group has not distinct change in Hb level(86.95±11.61)对（84.30±16.25），（P&gt;0.05. Conclusion: Hb is significantly increased after the use of rHuEPO and side effects were less with well tolerances.

Effect of Nutritional Supplementation on Illness Outcome in Adolescents with HIV on HAART: A Randomized, Double-Blind Clinical Trial.

To assess the effect of macronutrient and micronutrient supplementation on body mass index (BMI), hemoglobin (Hb), CD4 count, triglyceride levels, and morbidity among adolescents with human immunodeficiency virus (HIV) living in India. A prospective, randomized, double-blinded, placebo-controlled trial was conducted among 80 adolescents (10-19 y) with HIV on highly active antiretroviral therapy (HAART) for a minimum of 6 mo using simple randomization. Participants in the intervention arm received 400kcal and 15g protein as a powder daily and multivitamin tablets thrice weekly for 3 mo. Those in the placebo arm received a similar-appearing sachet containing 100kcal and 2g protein daily and a placebo tablet thrice weekly. Weight, height, BMI, Hb, CD4 count, triglycerides, and number of intercurrent illnesses were measured at 3 and 6 mo. At 6 mo, the intervention group showed an increase in weight from 36.4 ± 10.9kg to 39.7 ± 8.5kg and a significant increase in BMI from 16.6 ± 2.3kg/m2 to 17.5 ± 2.3kg/m2. Increase in CD4 count in the placebo arm was more than that in the intervention arm, but the difference between the arms was not statistically significant. Intervention group showed a pronounced rise in Hb from 9.7 ± 2.3g/dL to 11.4 ± 1.6g/dL, significant reduction in triglyceride levels from 99.2 ± 92.7mg/dL to 81.0 ± 12.8mg/dL and reduction in intercurrent illnesses from 32.5% to none. Nutritional supplementation of adolescents with HIV on HAART improves BMI, hemoglobin, and reduces triglyceride levels and intercurrent illnesses.

Does Postoperative Intravenous Ferric Carboxymaltose Hasten the Recovery of Hemoglobin in Patients Post Total Knee Arthroplasty?

Timely and effective iron supplementation may help reduce the incidence of postoperative anemia and its associated problems. In this study, we aim to assess the efficacy of intravenous ferric carboxy maltose (FCM) on improving hemoglobin(Hb) level posttotal knee arthroplasty (TKA). We retrospectively reviewed 263 patients who had undergone unilateral TKA with 157 patients in the study group (year 2019) and 106 in the control group (year 2016). Patients in the study group received FCM (500 mg IV) on postoperative day 1, whereas patients in the control group did not receive FCM or any other iron supplementation postoperatively. Hb levels were recorded preoperatively (Pr-Hb), postoperatively on day 3 (Day3-Hb) and postoperatively at 5(+1) weeks (Week5-Hb). Statistical analysis was performed using student's paired and unpaired t-tests. Pr-Hb and Day3-Hb levels were comparable in the control and study group, while Week5-Hb levels were significantly higher (P < .001) in the study group. The drop in Hb at Day3 from preoperative values was comparable between the two groups (P= 1.0). The rise in Hb from Day3 to 5 weeks was significantly higher in the study group as compared to the control group (P < .001). The difference between Pr-Hb and Week5-Hb was significantly lower (P < .001) in the study group compared to the control group. However, Week5-Hb in both groups remained lower than Pr-Hb (P < .001) in all patients. Intravenous FCM (500 mg) was found to be a safe method of iron supplementation to improve hemoglobin levels rapidly and consistently, post-TKA. We need to further study the additive effect of higher dose FCM (1000 mg) on hemoglobin recovery.

Efficacy of Ferrous Fumarate in Comparison to Carbonyl Iron in the Treatment of Iron Deficiency Anaemia during Pregnancy in Rajshahi, Bangladesh

Introduction: Iron deficiency represents a spectrum ranging from iron depletion to iron deficiency anaemia. In iron depletion, the amount of stored iron is reduced but the amount of transport and functional iron may not be affected. Iron deficiency is a major problem worldwide especially in women of reproductive age. Objectives: This study was designed to compare efficacy of two commonly used oral iron preparations among anemic pregnant women in private chamber of gynecologists and outdoor of Rajshahi Medical college hospital, Rajshahi, Bangladesh. Methods: We conducted analysis of data collected from Pregnant women between 18 to 40 years of age, &gt;8 weeks of gestation, having iron deficiency anaemia (serum hemoglobin levels &lt;10 gm/dl or serum ferritin &lt;30μg/l). The patients were divided into 2 groups (n=30) each and treated with Ferrous fumarate and carbonyl iron respectively. Hemoglobin gm/dl and serum Ferritin ng/dl were recorded after the interval of 3 months from baseline. Data was analyzed using SPSS 16. Efficacy variables between groups calculated using Chi square and T- test. Results: We observed that patients treated with Ferrous Fumarate (FF) showed significant rise in Hb 0.69(±0.83) which was greater than that of Carbonyl iron (CI) group 0.07(±1.11) g/dl. Mean (± SD) rise of serum ferritin was significantly higher in FF group (55.45 ±34.66) as compared to CI group (19.88 ±15.33) (t=5.14, df =58, P&lt;0.001). Conclusion: It can be concluded that, ferrous fumarate still can be considered better effective medication than Carbonyl iron for the treatment of Iron deficiency anemia in pregnancy.

Comparison of Efficacy and Tolerability of Ferrous Sulfate and Carbonyl Iron in Iron Deficiency Anemia in Pregnant Woman

Introduction: Iron deficiency anemia in pregnancy is common and causes a huge burden globally. Bangladesh is known to have a high prevalence of iron deficiency anemia in pregnant women. Hence, it is important to evaluate the efficacy and tolerability of drugs in treatment of iron deficiency anemia in pregnancy.&#x0D; Objective: The purpose of present study was to compare the efficacy and tolerability of Ferrous Sulfate and Carbonyl Iron in Iron Deficiency Anemia in pregnant women.&#x0D; Methodology: An observational prospective study was conducted in obstetric and gynae out – patient department of Sir Salimullah Medical College and Mitford Hospital. Woman between 16 – 28 weeks of pregnancy with haemoglobin level 7 – 10 g/dl with microcytic hypochromic blood film were included in this study. Pregnant women in 1st and 3rd trimester of pregnancy were excluded from the study. Among the study population one group was given Tablet Ferrous Sulfate and another group was given Capsule Carbonyl Iron.&#x0D; Results: There was significant and comparable rise in HB in 4th, 8th and 12th week in the two group. (p&lt;0.001). Carbonyl iron showed significantly more rise in Hb as compared to Ferrous Sulfate. Adverse effects were seen more in number and intensity with Ferrous Sulfate. Individual efficacy of both compounds was good but Carbonyl Iron was better tolerated.&#x0D; Conclusion: Carbonyl Iron is more effective and tolerable than Ferrous Sulfate in treatment of iron deficiency anemia in pregnancy.&#x0D; Sir Salimullah Med Coll J 2022; 30: 83-88

A Randomised Controlled Trial to Compare Injection Ferric Carboxymaltose and Oral Iron in Treating Iron Deficiency Anemia During Pregnancy.

Iron deficiency anemia (IDA) in pregnancy has a prevalence as high as 40-60% in different countries of the world. Oral iron is used to treat his commonest medical disorder in pregnancy. Ferrous sulphate is associated with considerable side effects. Ferric carboxymaltose (FCM) is a newer iron preparation which allows for single and higher dose (up to 1000mg) of IV iron infusion. This study was conducted to compare the efficacy of FCM and FS in treating IDA during pregnancy. A randomised control trial was done at a tertiary care centres involving 362 women (181 women each in FS and FCM group). The pregnant anemic women with IDA were enrolled between 18 and 34weeks of pregnancy. They were given 1000mg of FCM iv as single dose or were given FS tablets twice daily (120mg iron daily). The data were collected for rise in the Hb and serum ferritin over a period of 6weeks. Nine and 18 patients were lost to follow-up in the FCM and FS group, respectively. The data were analysed as per protocol analysis. FCM group women showed 2.6gm% rise in Hb compared to 1.7gm% of FS group. One hundred and sixty-six out of 172 women in FS group achieved anemia correction at 6weeks. No difference was observed in the neonatal outcome. No major side effects were observed in the either group. In our study, FCM was more effective than oral FS in increasing Hb in women with IDA during pregnancy. This clinical benefit with FCM was achieved without the concerns for safety and tolerability of the drug.

Comparative study of postpartum correction of anaemia by iron sucrose vs blood transfusion

Aim: The aim of the study is to know whether intravenous iron sucrose can be a better alternative in terms of safety and efficacy over blood transfusion in the treatment of anaemia in post-partum. Materials and methods: This are prospective study is conducted in obstetrics and gynaecology Department . All these women are randomly assigned (50 women total , 25 in each group) to receive either 2 doses of intravenous iron sucrose(Group A) or blood transfusion (Group B). Haemoglobin, hemocrit, mean corpuscular volume and serum ferritin estimation is done before treatment and after 1 wk. of correction in both groups to note the improvement in values and monitored for adverse reactions. Results: There is statically significant rise in haemoglobin , hemocrit , mean corpuscular volume , and serum ferritin levels when compared to baseline after 1 week of treatment in both groups. Statistically insignificant rise in mean Hb,Hct was observed when iron sucrose group is compared to blood transfusion group. Conclusion: Intravenous iron sucrose is safe , efficacious and cost-effective treatment for post-partum anaemia. It may be an attractive to blood transfusion which may be associated with minor and major reactions.

Effect of donor and red blood cells concentrate characteristics on recipient hemoglobin increment following red blood cells transfusion in pediatric patients.

Objectives:To determine the effects of donor and red blood cells concentrate characteristics on recipient hemoglobin increment following red blood cells transfusion in pediatric patients.Methods:This cross-sectional study was conducted at The Hematology & Transfusion Medicine Department of The UCHS & The Children’s Hospital, Lahore from 23rd December 2020 to 31st July 2021 after Institutional Ethical committee approval. After taking informed consent from parents/guardians, One hundred recipients receiving RBCs unit transfusion studied along with the respective donors. The donor’s details were recorded on a pre-designed proforma which included age, gender, Body Mass Index (BMI), CBC analysis (Hemoglobin [Hb] & Hematocrit) and blood group. Components’ preparation, storage and modifications details were also recorded. Hb levels of recipient were determined 12 hours prior to transfusion and 12-18 hours after transfusion. The data was analyzed on SPSS version 26.Results:Among recipients, the mean age was 5.25 ±3 years and male to female ratio was 1.16:1. The mean pre-transfusion Hb level of patients was 6.48g/dl (SD: 2.15) and mean post transfusion Hb was 8.824 g/dl (SD: 2.03) with a significant raise after transfusion (p< 0.001). Majority donors (60%) were between 18 to 30 years of age and mean age was 30.7 years (SD: 9.04). The hemoglobin increment was reduced for transfusion of RBC units from donor with greater age. Post- transfusion Hb rise was more in Rh D positive donations than Rh D negative (p< 0.0001). No significance of donors’ gender, BMI, Hb and hematocrit was found in relation to Hb increment. Among RBCs concentrate features, washing with normal saline found to have greater Hb increment, particularly in Thalassemia patients (p< 0.0001).Conclusion:Donors’ age and Rh blood group and red blood cell concentrates’ washing accounts for significant rise in recipient’s post-transfusion hemoglobin. These factors may be used to predict changes in recipients’ hemoglobin before transfusion.