Increase In Hb Research Articles

EFFECT OF HONEYBEE VENOM (APIS MELLIFERA) ON RESPIRATORY FUNCTIONS OF HYPERCHOLESTEROLEMIC MALE ALBINO RATS

Hypercholesterolemia can be defined as the presence of high plasma cholesterol levels, with normal plasma triglycerides, as a consequence of the rise of cholesterol and apolipoprotein B (apoB)-rich lipoproteins, called low-density lipoprotein (LDL)and characterized by very high levels on the blood cholesterol which is a risk factor of cardiovascular health. Medicines which formed from chemical compounds cause serious side effects that cause an imbalance in the body’s functions. Therefore, using of natural substances may be an innovative method for the treatment of diseases, as they do not have any side effects on human health. Bee venom can be used as a drug due to its beneficial effects on many disorders, such as neurological, cardiovascular, hematological, musculoskeletal, and dermatological disorders. In the present work, we found that treatment of hypercholesterolemic rats with bee venom (BV) revealed significant increases in Hb, Hct, and RBCs count and showed a significant increase in PaO2, % O2 saturation, O2 carrying capacity. These results suggest that BV can enhance respiratory functions of blood and can be used in respiratory diseases to enhance the respiration and hematological parameters. Also, BV could be used as a prophylactic agent (food protector) to protect us from the harmful effects of cholesterol.

Computational studies of ionic liquids as co-catalyst for CO2 electrochemical reduction to produce syngas using COSMO-RS

Transforming carbon dioxide (CO2) into value-added products through electrochemical reduction reaction (CO2ERR) is a promising technique due to its potential advantages using renewable energy. The main challenge is to find a stable catalytic system that could minimize the reaction overpotential with high faradaic efficiency and high current density. Ionic liquids (ILs) as electrolyte in CO2ERR have attracted attention due to the advantages of their unique properties in enhancing catalytic efficiency. For better performance, a systematic understanding of the role of ILs as electrocatalyst is needed. Therefore, this paper aims to correlate the performance of ILs as co-catalyst in (CO2ERR) with the lowest unoccupied molecular orbital (LUMO) energy level and the interaction energy as predicted by quantum chemical calculation using Conductor like Screening Model for Real Solvents (COSMO-RS) and Turbomole. The results show strong linearity (R2=0.98) between hydrogen bond energy (HB) and LUMO values. It is demonstrated that as HB increases, the LUMO value decreases, and the catalytic activity for CO2ERR also increases. This result allows further understanding on the correlation between the molecular structure and the catalytic activity for CO2ERR. It can serve as a priori prediction to aid in the design of new effective catalysts.

Effect of Cadmium and Spirulina platensis Administration on Hematological Parameters in Chickensa

One hundred chickens of one day of age were divided randomly into five groups of 20 birds each. After two weeks of adaptation, group I was kept in control, group II was fed with 0.2% Spirulina platensis powder till 90th day post treatment (DPT). Group III was administered 1.6 ppm cadmium as cadmium chloride monohydrate (CdCl2.H2O) in triple glass distilled water. Groups IV and V were administered 1.61 ppm cadmium in triple glass distilled water along with Spirulina platensis powder orally in standard recommended feed at the rate of 0.2% concentration. However, in Group V Spirulina platensis powder was given from 60th DPT till 90th DPT. For hematological studies, blood samples were collected from each group at 0, 15th, 30th, 45th, 60th, 75th and 90th DPT. There was a significant treatment dependent decrease in values of hemoglobin (Hb), packed cell volume (PCV), total erythrocyte count (TEC), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC), whereas a significant increase in mean corpuscular volume (MCV) in cadmium treated groups III and V as compared to group I. In groups III and V, significant increase in total leukocyte count (TLC), absolute lymphocyte count (ALC) and absolute heterophil count (AHC) were recorded. In group IV, significant decrease in Hb, PCV, TEC, MCH, MCHC, lymphocytes and significant increase in TLC, MCV, heterophils was observed as compared to groups III and V. It was concluded from the present study that cadmium fed at NOEL (1.61 ppm) levels for 90 days is toxic. Spirulina platensis fed concurrently with cadmium at NOAEL dose nullified the toxic effects of cadmium. However, Spirulina fed after accumulation of cadmium at NOEL dose is not able to reverse the adverse effects.

Прямой и обратный магнитоэлектрический эффект в орторомбических монокристаллах Dy-=SUB=-1-x-=/SUB=-Ho-=SUB=-x-=/SUB=-MnO-=SUB=-3-=/SUB=-

In this work, the magnetoelectric response in a series of Dy1-xHoxMnO3 crystals with substitution x from 0 to 0.4 was investigated. The measurement results showed that, as x increases, a decrease in both the polarization Pa and the magnitude of the susceptibility of the inverse magnetoelectric effect αba is observed. In addition, the field Hb increases, at which the Pc→Pa transition is observed, and the temperature range of the existence of the magnetoelectric response decreases. Thus, an increase in the substitution x suppresses the magnetoelectric effect in this series of compounds. The measurement results also indirectly indicate the prolongation of the Pa state and, consequently, of the magnetic state with a cycloid lying in the ab-plane by an external electric field Ea. The reported study was funded by Russian Foundation for Basic Research, Government of Krasnoyarsk Territory, Krasnoyarsk Regional Fund of Science to the research project No.20-42-243008.

Hematobiochemical Effects of Telakucha (Coccinia Indica) in Alloxan Induced Diabetic Rats

The study was undertaken to investigate the effects of Telakucha (Cocciniaindica) on blood glucose, serum total cholesterol, hematological parameters and body weight in alloxan induced diabetic rats. In this experiment 45 rats were selected for the trial purpose. The rats were divided into 3 equal groups, each containing 15 individuals (n=15) as follows: normal control (C) group, diabetic control (DC) group and diabetic treatment (DT) group. Diabetes was induced in diabetic control (DC) and diabetic treatment (DT) group with alloxan @ 200mg/kg body weight intraperitonially. Then diabetic treatment group (DT) was treated with 10% aqueous extract of Telakucha @500 mg/kg body weight. After 42 days of treatment, Telakucha extract reduced the amount of blood glucose significantly (P<0.001) in the group DT compared to DC from 32.03 ± 0.25 to 11.17 ± 0.08 mmol/L. Total cholesterol (TC) was also decreased significantly (P<0.001) in group DT compared to group DC from 121.85±0.27 to 112.42±0.14 mg/dL. In hematological study, DT group showed significant (P<0.001) increase in erythrocytes count and Hb (g%) content and decrease (P<0.001) in total leukocyte count after 42 days of treatment in contrast with DC group. The body weight was also increased significantly (P<0.001) in DT group. Based on present research it can be concluded that Telakucha (Cocciniaindica) can be used in the treatment of diabetes as an alternative to commercial medicine.
 Res. Agric., Livest. Fish.7(3): 431-438, December 2020

Complete Blood Count (CBC) Status among Hypertensive Subjects in Isiala Mbano, Imo State, South East, Nigeria

Aim: The Complete Blood Count (CBC) among hypertensive subjects in Isiala Mbano, Imo State, Nigeria West Africa were studied.
 Methodology: The American College of Cardiology/American Heart Association (2017) current definition of hypertension was used to ascertain, diagnoses and assigned eighty (80)hypertensive subjects after three different consecutive blood pressure check into tests groups. Other blood pressure measures such as pulse pressure and mean arterial pressure were calculated appropriately. Venous blood samples were collected with 5mls syringe and immediately emptied into EDTA container for complete blood count analysis.
 Results: The results showed increase in RBC count, HB, PCV and decrease in MCV among hypertensive subjects compared with normotensive subjects. It was statistically insignificant in all age groups. No changes were seen in MCHC and MCH. The results also, showed increase in PLTS count. The increase in PLTS count was statistically significant at P<0.05 and <0.001 among hypertensive age groups 36-65yrs and >66yrs respectively. Increase in PLTS count among 20-35yr age group was not significant. There were increase in WBC count among hypertensive subjects compared with normotensive subjects in all age groups. It was statistically significant at P<0.05 and <0.001 among hypertensive age groups 36-50yrs and >66yrs respectively. Neutrophil was increased in all age groups and was statistically significant at P<0.05 except 20-35yr age group. No changes were seen on lymphocytes, monocytes, eosinophils and basophils.
 Conclusion: Haematological parameters investigated could predict possible cardiovascular abnormalities such as hypertension.

Sustained Induction of Fetal Hemoglobin by Pulse Butyrate Therapy in Sickle Cell Disease

High levels of fetal hemoglobin (Hb F) protect from many of the complications of sickle cell disease and lead to improved survival. Butyrate and other short chain fatty acids were previously shown to increase Hb F production in erythroid cells in vitro and in animal models in vivo. However, butyrates are also known to inhibit the proliferation of many cell types, including erythroid cells. Experience with the use of butyrate in animal models and in early clinical trials demonstrated that the Hb F response may be lost after prolonged administration of high doses of butyrate. We hypothesized that this loss of response may be a result of the antiproliferative effects of butyrate. We designed a regimen consisting of intermittent or pulse therapy in which butyrate was administered for 4 days followed by 10 to 24 days with no drug exposure. This pulse regimen induced fetal globin gene expression in 9 of 11 patients. The mean Hb F in this group increased from 7.2% to 21.0% (P <.002) after intermittent butyrate therapy for a mean duration of 29.9 weeks. This was associated with a parallel increase in the number of F cells and F reticulocytes. The total hemoglobin levels also increased from a mean of 7.8 g/dL to a mean of 8.8 g/dL (P <.006). The increased levels of Hb F were sustained in all responders, including 1 patient who has been on pulse butyrate therapy for more than 28 months. This regimen, which resulted in a marked and sustained increase in Hb F levels in more than two thirds of the adult sickle cell patients enrolled in this study, was well tolerated without adverse side effects. These encouraging results require confirmation along with an appropriate evaluation of clinical outcomes in a larger number of patients with sickle cell disease.

Betroot (Beta vulgaris) administration to anemic pregnant women for increasing hemoglobin level

Objective: To identify the effectiveness of beet juice administration on hemoglobin level of anemic pregnant women.Materials and Methods: This was an experimental quantitative study using pretest-posttest design with a total sample of 30 patients who were divided into 2 groups of treatment groups (beetroot + Fe) and control group (Fe). The treatment was carried out for 14 days. Before and after the treatment, the samples were subjected to hemoglobin examination. Data in this study were the difference between pre-test and post-test values, the results of normality test with Shapiro Wilk, and, to identify the difference between pre-test and post-test, the results of Wilcoxon Test for abnormal data and Paired T-Test for normal data.Results: Mann Whitney Test results between treatment and control groups revealed p (0.023) &lt; alpha (0.05). There was a significant difference in hemoglobin levels between TM III pregnant women with anemia receiving beets and those receiving Fe tablets only.Conclusion: Minimum Hb increase before and after the administration of Fe and beetroot juice to pregnant women was 17.7 gr% and the maximum Hb level was 0.8 gr%.

A 1 g dose of intravenous iron is sufficient to treat iron deficiency anaemia.

One hundred and ninety-four patient episodes were audited for response to a standardised 1 g intravenous iron infusion for medical outpatients with iron deficiency anaemia. Patients received either ferric carboxymaltose or iron polymaltose. At 5-7 weeks after infusion, mean increase in Hb was 26.7 g/L and ferritin was 161 mcg/L, and only one patient had Hb <100 g/L. This reassures that 1 g dose of intravenous iron is sufficient for most patients, with benefits for treatment costs and patient convenience.

Differential effects of socio-demographic factors on maternal haemoglobin concentration in three sub-Saharan African Countries

Low Haemoglobin concentration (Hb) among women of reproductive age is a severe public health problem in sub-Saharan Africa. This study investigated the effects of putative socio-demographic factors on maternal Hb at different points of the conditional distribution of Hb concentration. We utilised quantile regression to analyse the Demographic and Health Surveys data from Ghana, Democratic Republic of the Congo (DRC) and Mozambique. In Ghana, maternal schooling had a positive effect on Hb of mothers in the 5th and 10th quantiles. A one-year increase in education was associated with an increase in Hb across all quantiles in Mozambique. Conversely, a year increase in schooling was associated with a decrease in Hb of mothers in the three upper quantiles in DRC. A unit change in body mass index had a positive effect on Hb of mothers in the 5th, 10th, 50th and 90th, and 5th to 50th quantiles in Ghana and Mozambique, respectively. We observed differential effects of breastfeeding on maternal Hb across all quantiles in the three countries. The effects of socio-demographic factors on maternal Hb vary at the various points of its distribution. Interventions to address maternal anaemia should take these variations into account to identify the most vulnerable groups.

Rapamycin (Sirolimus) and Rap-536 Increase Red Blood Cell Parameters through Distinct Mechanisms in Wild-Type and Thalassemic Mice

Luspatercept, a fusion protein composed of a modified activin receptor type-2B (ActRIIB) and IgG1 Fc, is a novel erythroid maturation agent that has been shown to increase red blood cell (RBC) and hemoglobin (Hb) levels. Luspatercept binds to and sequesters several endogenous transforming growth factor-beta superfamily ligands, thereby diminishing Smad2/3 signaling. RAP-536, the murine analog of luspatercept, has been shown to induce erythroblast maturation and increase RBC, Hb, and hematocrit levels in wild-type (WT) mice and in murine disease models of beta-thalassemia and myelodysplastic syndromes. Previous studies have shown that rapamycin (sirolimus), an mTOR inhibitor, improved anemia in a mouse model of beta-thalassemia by activating the autophagy pathway. In this study, rapamycin was tested in combination with RAP-536 by treating WT mice and th3/+ mice (a beta-thalassemia disease model; B6.129P2-Hbb-b1tm1Unc Hbb-b2tm1Unc/J) with vehicle, RAP-536 10 mg/kg twice weekly, rapamycin 4 mg/kg daily, or RAP-536 plus rapamycin for 2 weeks. Single-agent dosing with either RAP-536 or rapamycin increased RBC, Hb, and hematocrit levels significantly compared with vehicle treatment in both WT and th3/+ mice (Figure). The percentage increase in RBC, Hb, and hematocrit levels upon RAP-536 or rapamycin administration was substantially higher in th3/+ mice than in WT mice. Interestingly, much higher and significant increases in RBC and Hb levels in both WT and th3/+ mice, and in hematocrit levels in th3/+ mice, were observed with RAP-536 plus rapamycin, when compared with the single agents. For example, in th3/+ mice, the increase in Hb levels compared with vehicle control was 19.2% with RAP-536 alone, 13.0% with rapamycin alone, and 44.7% with RAP-536 plus rapamycin (Figure). In th3/+ mice, RAP-536 plus rapamycin treatment also significantly reduced spleen enlargement compared with vehicle (P &amp;lt; 0.001). RAP-536 increased and rapamycin decreased overall reticulocyte levels and immature reticulocyte relative percentages in whole reticulocyte populations in the blood of WT mice, suggesting that RAP-536 and rapamycin have different mechanisms of action through which they increase RBC and Hb levels. Altogether, these preclinical results provide a rationale for combining rapamycin, and potentially other mTOR inhibitors, with luspatercept to treat anemia associated with beta-thalassemia. Disclosures Acar: Bristol Myers Squibb: Ended employment in the past 24 months. Jupelli:Bristol Myers Squibb: Current Employment. MacBeth:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Schwickart:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.

Measuring Reticulocyte Hemoglobin Content As a Marker for Iron Deficiency and Response to Therapy Represents a Paradigm Shift in Care

It is estimated anemia affects over 30% of the world's population, with iron deficiency (ID) the overwhelmingly most common cause. Whether absolute due to blood loss and/or iron sequestration to underlying morbidity, the need for repletion especially in females, is a formidable medical issue. The diagnosis of iron deficient erythropoiesis has been traditionally based on the biochemical parameters ferritin and percent transferrin saturation (TSAT), mean cell volume and hemoglobin (Hb) concentration. In recent years, reticulocyte Hb content has emerged as a parameter helpful in identifying iron deficient erythropoiesis and informing a need, or lack thereof, for replacement. 556 consecutive, non-selected patients referred for diagnosis and/or treatment of anemia were included in this diagnostic study to compare the performance of reticulocyte hemoglobin equivalent (RET-He) versus traditional biochemical markers for diagnosis and treatment of IDA. CBC, serum ferritin, iron and TSAT were performed as clinically indicated. RET-He was measured with a Sysmex XN-450 analyzer on the residual CBC sample. 556 patients were studied at baseline and 150 were subsequently treated with intravenous (IV) iron. 240/556 were seen at follow-up, with 57 treated and 183 not treated with IV iron. At baseline, ret-He, positively correlated with Hb (Spearman correlation (rho)=0.365, P &amp;lt; 0.001), MCV (rho=0.576, P &amp;lt; 0.001), MCH (rho=0.777, P &amp;lt; 0.001), serum iron (rho=0.526, P &amp;lt; 0.001) and TSAT (rho=0.492, P &amp;lt; 0.001). Serum iron, and TSAT (but not serum ferritin or MCV, or absolute reticulocyte count) positively correlated with Hb concentrations. Based on either a serum ferritin &amp;lt;30 ng/ml and/or a TSAT&amp;lt; 20%, 241/556 (43.4%) patients were diagnosed as iron deficient. Anemia was present in 64/241 of the iron deficient patients (26.6%). Despite the limitations of the biochemical markers outlined above, we performed ROC analysis assessing the value of RET-He in identifying iron deficiency as defined by serum ferritin &amp;lt;30 ng/mL or transferrin saturation &amp;lt;20%. ROC analysis demonstrates a reasonable performance for RET-He (AUC= 0.733, 95% CI: 0.692, 0.775), with a cut-off value of &amp;lt;30.7 pg yielding 68.2% sensitivity and 69.7% specificity. Using both Hb and RET-He in a multivariable ROC analysis does not provide an improved AUC, as compared to just using RET-He (AUC=0.605 vs.0.733). IV iron administration was associated with significant increases in Hb, MCV, MCH, RET-He, serum ferritin, iron and TSAT, whereas in the no-IV iron cohort, there was a small reduction in RET-He and small increases in MCV and MCH, with no significant variations in Hb and in the other parameters. Serum ferritin was below 30 ng/mL in 18/57 (32%) of the patients requiring IV iron and in 19/183 (10.4%) of those not requiring iron at visit 1. These values changed to 4/57 (7%) (P=0.002) and 23/183 (13%) (P=0.623) at visit 2, respectively. Regression analysis for Hb response following IV iron showed that baseline RET-He values are predictive of Hb response, with every unitary increase in RET-He corresponding to a blunting of the Hb change by -0.19 g/dl (95% CI: -0.27, -0.11; P &amp;lt; 0.001). Changes in RE-He associated with IV iron administration are also predictive of the Hb response, with every additional unit increase in RET-He corresponding to a 0.21 g/dL increase in Hb (95% CI: 0.13, 0.28; P &amp;lt; 0.009). ROC analysis for the capability to predict Hb response among the 57 patients receiving IV iron shows that a value of baseline RET-He &amp;lt; 28.5 pg together with a baseline Hb value &amp;lt; 10.3 g/dL provide the highest Youden's index for predicting Hb response &amp;gt; 1.0 g/dl, with sensitivity of 84% and specificity of 78%. The Figure presents data for the 21/57 patients who had RET-He &amp;lt; 28.5 pg and Hb &amp;lt; 10.3 g/dL vs the 36/57 who did not. The present data show that an abnormally low ret-He value (&amp;lt; 28.5 pg) identifies patients who will respond to iron replacement, obviating delays to obtain standard iron parameters. Baseline and changes in ret-He also associate with Hb response. Given the enormous prevalence of ID in the general population the use of the ret-He, which is available with the CBC on the autoanalyzer, informs need for iron replacement, or lack thereof, represents an increase in convenience for patient and physician, decreases costs, streamlines care and represents an improvement in the treatment paradigm of one of the commonest maladies on the planet. Figure 1 Disclosures Auerbach: AMAG: Research Funding; Sysmex: Research Funding. Brugnara:American Journal of Hematology: Other; Sysmex America Inc.: Consultancy.

Real-World Effectiveness of Voxelotor for Treating Sickle Cell Disease in the US

Real-World Effectiveness of Voxelotor for Treating Sickle Cell Disease in the US

Safety and Efficacy of CTX001 in Patients with Transfusion-Dependent β-Thalassemia and Sickle Cell Disease: Early Results from the Climb THAL-111 and Climb SCD-121 Studies of Autologous CRISPR-CAS9-Modified CD34+ Hematopoietic Stem and Progenitor Cells

Safety and Efficacy of CTX001 in Patients with Transfusion-Dependent β-Thalassemia and Sickle Cell Disease: Early Results from the Climb THAL-111 and Climb SCD-121 Studies of Autologous CRISPR-CAS9-Modified CD34+ Hematopoietic Stem and Progenitor Cells

Efficacy and Safety of Voxelotor in Adolescents and Adults with Sickle Cell Disease: HOPE Trial 72-Week Analysis

Background: Sickle cell disease (SCD) is a lifelong, inherited disorder characterized by mutations in the hemoglobin (Hb) subunit β gene that leads to the production of sickle hemoglobin (HbS). When HbS is deoxygenated, polymerization leads to red blood cell sickling and damage, resulting in hemolysis, chronic anemia, and episodic vaso-occlusive crises (VOCs). Patients with SCD are at an increased risk of developing long-term complications, including stroke, leg ulcers, and other end-organ damage. Lower Hb levels highly correlate with increased morbidity and early mortality in SCD. Voxelotor (Oxbryta®) is an oral, once-daily HbS polymerization inhibitor indicated for the treatment of SCD in adults and adolescent patients ≥12 years of age. The 24-week analysis of the HOPE trial demonstrated that treatment with voxelotor 1500 mg resulted in a significantly greater proportion of patients achieving a &amp;gt;1 g/dL Hb increase compared with placebo (51.1% vs 6.5%, P&amp;lt;0.001), which was associated with concordant improvements in hematological markers of hemolysis (indirect bilirubin and reticulocyte percentage). Here we report the evaluation of efficacy and safety of voxelotor 1500 mg at 72 weeks, the conclusion of the placebo-controlled HOPE trial. Methods: In the randomized, double-blinded, placebo-controlled, phase 3 HOPE trial, adults and adolescents (aged 12-65 years) with SCD were randomized to receive voxelotor (1500 mg or 900 mg) or placebo. Included patients had an Hb level of 5.5 to 10.5 g/dL at enrollment and 1 to 10 vaso-occlusive crises in the 12 months prior to screening. Concurrent hydroxyurea was allowed if the dose had been stable for ≥90 days at enrollment. Changes from baseline in Hb and hemolysis markers (absolute and percentage reticulocyte, indirect bilirubin levels, and lactate dehydrogenase levels) and safety were assessed at week 72. Results: 89% (95% CI, 82.4% to 95.4%) of patients receiving voxelotor 1500 mg achieved a Hb increase of &amp;gt;1 g/dL at 1 or more time points during the 72-week treatment period compared with 25% (95% CI, 16.2% to 33.8%) of those receiving placebo (P&amp;lt;0.001). The mean change in Hb from baseline at week 72 was 1.0 g/dL in patients treated with voxelotor 1500 mg compared with 0.0 g/dL in patients receiving placebo (Figure 1; P&amp;lt;0.001). Mean change from baseline to average Hb throughout the 72-week duration was 1.26 g/dL in patients treated with voxelotor 1500 mg. Consistent with the week 24 analysis, significant improvements in markers of hemolysis (assessed by difference in adjusted mean percent change versus placebo) were seen in indirect bilirubin (-26.6% [95% CI, -40.2% to -12.9%]) and reticulocyte percentage (-18.6% [95% CI, -33.9% to -3.3%]) in the voxelotor 1500 mg group relative to placebo, with favorable trends of reduction in other markers, such as absolute reticulocyte count (-5.8% [95% CI, -23.4% to 11.9%] and lactate dehydrogenase (-4.8% [95% CI, -13.8% to 4.1%]). The overall incidence rate of VOCs was numerically lower in the 1500 mg arm compared with placebo, but was not statistically significant. Rates of non-SCD and SCD-related treatment-emergent adverse events were similar between the treatment groups, with no new safety signals noted through week 72. Conclusions: Voxelotor 1500 mg resulted in durable improvements in Hb levels and markers of hemolysis out to 72 weeks of treatment, with approximately 90% of patients achieving an increase in Hb &amp;gt;1 g/dL at 1 or more time points during the study. Treatment with voxelotor remained well tolerated, with no new safety signals detected with longer-term follow-up. These results support the sustained and chronic use of voxelotor to reduce anemia and hemolysis, thereby potentially mitigating the associated morbidity and mortality of SCD. Disclosures Howard: Imara, Inc., Novartis, Resonance Health: Honoraria; Agios, Forma Therapeutics, Inc., Global Blood Therapeutics, Imara, Inc., Novo Nordisk, Novartis: Membership on an entity's Board of Directors or advisory committees. Ataga:Editas Medicine: Honoraria; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shire/Takeda: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Forma Therapeutics: Consultancy; Modus Therapeutics: Honoraria; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees. Achebe:Global Blood Therapeutics: Consultancy. Hassab:Global Blood Therapeutics: Research Funding. Agodoa:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Tonda:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Gray:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Lehrer-Graiwer:Global Blood Therapeutics: Other: Former employee and former equity holder. Vichinsky:Pfizer: Research Funding; Agios: Research Funding; Global Blood Therapeutics: Consultancy.

Low Dose Rituximab Plus High Dose Dexamethasone As First-Line Treatment for Autoimmune Hemolytic Anemia

Introduction Corticosteroids are the first line therapy for autoimmune hemolytic anemia (AIHA), but are associated with significant adverse events, dependency and frequent relapses. Rituximab is reserved for severe or steroid-resistant disease. Low-dose rituximab is also effective, but its efficacy in the first line has been poorly described. We report our results with this combination. Methods Adults older than 16 years newly diagnosed with warm antibody AIHA either primary or secondary were included. Patients systematically received dexamethasone 40 mg for 4 days followed by a 1 mg/kg rapid prednisone taper plus rituximab 100 mg weekly for 4 doses. Our primary outcome was response at day 28 based on the First International Consensus Meeting (complete response: normalization of Hb, no evidence of hemolysis and absence of transfusions; response: increase of Hb by &amp;gt;2g/dl, or normalization of biochemical resolution of hemolysis or absence of transfusion in 7 days), secondary outcome was event-free survival with an event defined as a laboratory or clinical relapse or loss of response. Results Sixteen patients were treated with low-dose rituximab during the study period, ten women (62.5%), six men (37.5%). The median age was 34 years (range, 17-78). Three (18.75%) were secondary to lupus erythematosus. The median follow-up was 20 months (range, 0.4-66). Most received 4 doses of rituximab (87.5%). All patients responded at day 28, (100%) 31.2% achieved a complete response (CR). Subsequently, 81.3% achieved CR. Ten (62.5%) were considered steroid-dependent, however, most discontinued treatment without loss of response (75%). The event-free survival was 63.8% to 5 years. Conclusion Low-dose rituximab therapy as a first-line in AIHA showed encouraging results as most patients were able to discontinue treatment without relapse. Disclosures Gomez-Almaguer: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

FT-4202, an Allosteric Activator of Pyruvate Kinase-R, Demonstrates Proof of Mechanism and Proof of Concept after a Single Dose and after Multiple Daily Doses in a Phase 1 Study of Patients with Sickle Cell Disease

FT-4202, an Allosteric Activator of Pyruvate Kinase-R, Demonstrates Proof of Mechanism and Proof of Concept after a Single Dose and after Multiple Daily Doses in a Phase 1 Study of Patients with Sickle Cell Disease

Phase 1 Multiple Ascending Dose Study of Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Mitapivat (AG-348) in Subjects with Sickle Cell Disease

Phase 1 Multiple Ascending Dose Study of Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Mitapivat (AG-348) in Subjects with Sickle Cell Disease

Efficacy and Safety of Luspatercept Treatment in Patients with Myelodysplastic Syndrome/Myeloproliferative Neoplasm with Ring Sideroblasts and Thrombocytosis (MDS/MPN-RS-T): A Retrospective Analysis from the Medalist Study

Efficacy and Safety of Luspatercept Treatment in Patients with Myelodysplastic Syndrome/Myeloproliferative Neoplasm with Ring Sideroblasts and Thrombocytosis (MDS/MPN-RS-T): A Retrospective Analysis from the Medalist Study

Effective Treatment of Cold Agglutinin Disease/Cold Agglutinin Syndrome with Ibrutinib: An International Case Series

Background In cold agglutinin mediated autoimmune hemolytic anemia (cAIHA), anti-red blood cell autoantibodies lead to complement-mediated hemolysis with or without symptoms of acrocyanosis after exposure at low temperatures. cAIHA can be divided into cold agglutinin disease (primary CAD) and cold agglutinin syndrome (CAS). The latter is secondary to diseases such as B-cell malignancies including CLL, infections or autoimmune disorders. In primary CAD, more than 90% of patients have a monoclonal IgM (mostly low level) and often a small bone marrow B-cell clone. There is no approved treatment. For patients with significant hemolytic anemia or acrocyanosis despite thermal protection, rituximab is the most accepted first line treatment with an overall response rate of 50% and median duration of response &amp;lt;1 year. Cytotoxic combinations such as rituximab-bendamustine produce more sustained remissions, although with concerns for long-term adverse effects and stem cell toxicity. Studies involving complement inhibitors are showing promising results on hemolysis, although cold induced peripheral symptoms (IgM mediated rather than complement-mediated) will not improve. Recent international guidelines on cAIHA suggest treatment with the Bruton tyrosine kinase (BTK)-inhibitor ibrutinib in refractory patients with cAIHA (Jäger et al Blood Rev 2020). Indeed, the underlying pathophysiology of cAIHA suggest that BTK inhibition could be effective. Aims To evaluate the efficacy of ibrutinib on anemia, hemolysis and acrocyanosis in patients with cold agglutinin-mediated AIHA (CAD/CAS). Methods An international retrospective study was undertaken of cAIHA patients (CAD/CAS) treated with BTK inhibition using a preformed questionnaire. For eligible patients, laboratory and clinical data regarding underlying disease, bone marrow pathology, hemolytic parameters and patient-reported acrocyanosis were collected at diagnosis, 30 days, 3 months, 6 months and 12 months and last date of follow up. Hemoglobin (Hb) response was considered none (NR), partial (PR, &amp;gt;2 g/dL Hb increase or &amp;gt;10g/dL) or complete (CR, &amp;gt;12g/dL). Adverse events were graded according to the Common Terminology Criteria, version-5.0 (2017). Results So far, 10 patients with cAIHA treated with a BTK-inhibitor (all involving ibrutinib) could be included in the study. Patients were followed from April 2014 until June 2020 at 5 centers (Italy (2), Norway, The United Kingdom and The United States). Median duration of follow up was 20 months (1-74 months). The main findings are summarized in table 1. The indication to start treatment was cAIHA based in all but 1 case (CLL). Median previous number of therapies was 2. All patients had a complement-mediated hemolytic anemia, 7 were transfusion-dependent, and 7 reported symptoms of acrocyanosis at the initiation of ibrutinib. After initiation of ibrutinib, all patients showed an improvement in hemoglobin (Median rise: 4.4 g/dL) resulting in 1 PR and 9 CR. All 7 transfusion-dependent patients became transfusion independent (5 within 30 days). In all but 1 patient, markers of hemolysis (LDH, bilirubin) improved after initiation of ibrutinib (see Figure 1). All 7 patients with acrocyanosis reported clear clinical improvement, with complete resolution of symptoms in 5. There was 1 adverse event (grade 1 bleeding). Data collection is still ongoing and future updates are expected. Conclusion Data show that ibrutinib is effective in the treatment of cAIHA with a notable and brisk improvement of both the hemolytic anemia as well as the cold induced peripheral symptoms. Although preliminary, these promising data support further research of BTK-inhibitor based treatment of cAIHA (CAD/CAS) in a prospective study. Disclosures Berentsen: Alexion, Apellis, Bioverativ and Janssen-Cilag: Other: Travel grants ; Alexion, Apellis, Bioverativ, Janssen-Cilag, True North Therapeutics: Honoraria; Apellis, Bioverativ, Momenta Pharmaceuticals and True North Therapeutics: Consultancy; Mundipharma: Research Funding. Castillo:TG Therapeutics: Research Funding; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Kymera: Consultancy; Abbvie: Research Funding; Janssen: Consultancy, Research Funding. Treon:Bristol-Meyer-Squibb: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding. D'Sa:Sanofi: Honoraria; BeiGene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. OffLabel Disclosure: BTK-inhibitors (ibrutinib/acalabrutinib) are not yet indicated for the use in (primairy) cold autoimmune hemolytic anemia (cAIHA). However it is indicated for use in Waldenstrom macroglobulinemia (WM) and chronic lymphatic leukemia (CLL). Here we report retrospective data on a cohort of cases treated with ibrutinib for cAIHA mostly secondary to WM or CLL.