Improvement In Hemoglobin Levels Research Articles

Complement Blockade with C1 Esterase Inhibitor in Severe C3d Positive Autoimmune Hemolytic Anemia

Autoimmune hemolytic anemia (AIHA) is defined as the development of autoantibodies against red blood cell (RBC) antigens. AIHA is diagnosed in the presence of hemolysis and a positive direct antiglobulin test (DAT) for IgG and/or complement C3d. AIHA is classified as warm, cold or mixed based on the temperature at which the autoantibody is most active. The most clinically severe anemia is usually associated with AIHA in which C3d is detected on DAT. The classical complement pathway is activated in AIHA when antigen-autoantibody complexes on the RBC surface bind to the complement protein C1q. This ultimately results in the generation of C3b. C3b is both an opsonin and an additional proteolytic enzyme. C3b deposition targets the RBC for phagocytosis by macrophages of the reticuloendothelial system resulting in extravascular hemolysis. C3b can also continue activation of complement on the RBC membrane resulting in formation of the membrane attack complex (MAC) and cell lysis. C3b is degraded into C3d, which is identified by the DAT (Bartolmas 2015). Severe anemia and its immediate consequences, the difficulty identifying suitable units for acute RBC transfusion, the likelihood of causing additional hemolysis as well as concerns for stimulating additional antibody production with transfusion make these patients particularly challenging to treat. Current standard treatment consists of steroids with or without rituximab. This treatment paradigm does not, however, address the acute and urgent management of life threatening anemia in many of these patients. C1 esterase inhibitor (C1-INH) is a member of the serine protease inhibitor family and interacts with C1 esterase to block activation of the classical pathway of complement. Case reports have demonstrated that C1-INH can prevent C3-mediated lysis of PNH erythrocytes (DeZern 2014) and augment survival of transfused RBCs in a patient with DAT C3d positive autoimmune hemolytic anemia (Wouters 2013). We hypothesized that minimizing or inhibiting the generation of C3b with C1-INH in patients with either severe cold autoantibody AIHA or a mixed AIHA would rapidly reduce acute hemolysis. We report our clinical experience using a novel approach in the acute management of severe AIHA using the commercially available C1-INH, Berinert. The four patients we identified with either cold or mixed AIHA (Table 1) were between the ages of 58 and 63. All patients presented with clinically severe anemia and required urgent management. Three of the 4 had a co-morbid condition associated with AIHA. All patients received prednisone (1mg/kg) and the commercially available C1-INH at a dose of 20mcg/kg daily from the day of admission for a minimum of 6 days to a maximum of 20 days. Patients 2, 3, and 4 also received 4 weekly doses of rituximab during the course of treatment. The average increase in mean hemoglobin was 79% (presentation mean 4.5gm/dL- end of C1-INH mean 7.95gm/dL) during C1-INH administration. An average of 1.25(0-2) units of packed RBC per patient were transfused during C1-INH administration. Additional measures of ongoing hemolysis including mean LDH which decreased by an average of 72% (presentation mean 1358u/L to end of C1-INH mean 356u/L) and mean haptoglobin which increased in all patients from < 8mg/dL to 111mg/dL after C1-INH. Of note, patient 1 had cold agglutinin titers measured prior to C1-INH administration at 1:128 and repeated after two days of C1-INH administration revealed a decrease to 1:32. This retrospective review of patients demonstrates that utilizing C1-INH in conjunction with standard therapy is safe and results in rapid improvement of hemoglobin levels in patients with DAT/C3d positive AIHA. We hypothesize the inhibition of C1q-C4 interaction rapidly reduces C3b deposition on the RBC membrane decreasing both extra and intravascular RBC destruction. CI-INH therapy allowed successful management of these acutely ill patients with minimal RBC transfusions. We hypothesize that decreasing the exposure to additional antigenic stimulation may shorten the acute exacerbation of hemolysis. The optimal form and schedule of C1-INH therapy for AIHA remains to be determined. Based on these observations the role of inhibitors of the classical pathway of complement as both a single modality and in conjunction with standard therapy in the management of AIHA deserves further investigation. Table Table. Disclosures Broome: Alexion Pharmaceuricals: Honoraria; True North Therapeutics: Honoraria.

Rationale for Therapy Discontinuation in Patients with Lower-Risk Transfusion-Dependent Myelodysplastic Syndromes (MDS)

Introduction: Approximately 50% of patients with MDS are anemic at initial diagnosis, with many becoming transfusion dependent (TD), necessitating the introduction of therapy with a goal of achieving transfusion independence (TI). In addition to transfusions, treatments to improve hemoglobin levels have historically been limited to erythropoiesis-stimulating agents (ESAs), whereas patients with more advanced disease may require treatment with a hypomethylating agent (HMA) (azacitidine [AZA] or decitabine [DAC]) or lenalidomide (LEN). As there is no predetermined treatment course, these therapies are continued until unacceptable toxicity, lack/loss of response, or disease progression. We examined treatment patterns, clinical outcome(s) of patients with MDS, and the physician's report of reason for treatment discontinuation (previously shown to vary from patients' perspectives) in patients who became TD at or after MDS diagnosis (Gerds et al. Blood 2014;124:abstract 2642).Methods:Data were derived from disease-specific physician surveys and patient charts, which provided information on demographic, treatment, and outcome data on lower-risk TD MDS patients. Patient inclusion criteria were: age ≥ 18 years, diagnosis of Low/Intermediate-risk MDS (International Prognostic Scoring System defined) 2-6 years prior to study entry, and becoming TD at least once during the minimum follow-up of 24 months. TD was defined as having received ≥ 2 transfusions within 8 weeks during the follow-up period. Patients who progressed to higher-risk disease or acute myeloid leukemia prior to becoming TD, had an additional malignancy, or were in an MDS clinical trial were excluded. Demographics, disease history, treatment history, TI, and reasons for treatment discontinuation were collected and reported descriptively.Results: A total of 239 physicians provided information on 1,221 lower-risk TD MDS patients. The median age of patients was 65 years (range 27-95 years), 56.3% were male, and median time since diagnosis was 3.2 years (range 2-6 years). Along with packed red blood cell transfusions, 354 patients (29%) were prescribed LEN [of whom 12.7% had del(5q)], 348 patients (28.5%) were prescribed ESAs, and 32 patients (2.6%) were prescribed HMAs. During the follow-up period, 31.3% of ESA patients discontinued therapy (at a median of 12 months; range 3-47 months), 32% of HMA patients discontinued therapy (at a median of 10 months; range 3-52 months), and 26% of LEN patients discontinued therapy (at a median of 13 months; range 2-30 months). In the LEN-treated group, only 9.8% of patients who discontinued therapy had del(5q). The main reason cited for treatment discontinuation across therapy groups reported by physicians was "patients completing the scheduled course of treatment" (28.2%), which occurred in 32.6%, 20.2%, and 22.6% of the LEN, ESA, and HMA groups, respectively. Other reported reasons for discontinuation included "insufficient initial response" (20.0%), "patients no longer responding to therapy" (19.0%), "disease progression" (18.0%), "death" (13.3%), and "worsening hemoglobin levels" (12.8%). Across therapy groups, "patient preference to stop therapy" was reported less frequently (9.7%), occurring in 7.6%, 8.3%, and 12.9% of the LEN, ESA, and HMA groups, respectively.Conclusions:Over 30% of TD lower-risk MDS patients receiving LEN, ESAs, AZA, or DAC discontinued therapy. Per physician reports, the most frequent reason for discontinuation of therapy was completion of scheduled treatment course, which is in stark contrast to recommendations in consensus guidelines, as MDS is a chronic disease in which treatment should be continued ad infinitum. The significant number of patients who stop therapy for alternative reasons suggests opportunities for further investigation. Education on the expected duration of therapy is essential to help support physicians and inform patients about optimal treatment decisions in the care of all MDS patients. DisclosuresGupta:Kantar Health: Employment; Celgene Corporation: Consultancy, Research Funding. Binder:Celgene Corporation: Employment, Equity Ownership. Carraway:Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Research Funding, Speakers Bureau; Baxalta: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. Hawthorne:Kantar Health: Employment; Celgene Corporation: Consultancy, Research Funding. King-Concialdi:Kantar Health: Employment; Celgene Corporation: Consultancy, Research Funding. McGuire:Celgene Corporation: Employment, Equity Ownership.

ВПЛИВ КОРМОВИХ ДОБАВОК НА ПРОДУКТИВНІСТЬ, ГЕМАТОЛОГІЧНІ ТА ІМУНОЛОГІЧНІ ПОКАЗНИКИ КРОВІ КУРЧАТ–БРОЙЛЕРІВ

The results of the influence of feed additives: acidulent Versal liquid and probiotic bifidobacteria PKB on the growth dynamics and some hematological and immunological parameters of broiler chickens are presented in this article. The research was conducted on 30 broiler chicks. There were formed 3 groups. There were 10 chicks in each of them: a control group didn't get any feed additives; 1–st experimental group got feed and acidulent Versal liquid solution at the recommended dose of 1 ml /1 l of water; 2–nd experimental group got feed with probiotics bifidobacteria PKB at the recommended dose of 1g / 1kg of feed and acidulent Versal liquid solution at the recommended dose of 1 g/1 l of water. The 15th and 30th day blood were collected for hematological and immunological parameters checking.It was found, chicks that have got feed additives achieved more intensive increasing of average live weight and daily gain during this period. The live weight of broiler chicks from the second experimental group was higher at 76.5 grams, compared with the control and the 136.6 h – compared with I research group in case of using acidified and probiotics bifidobacteria. Average daily increasing were 49.93 g in the control group, 48.21 g and 52.36 g according to another experimental groups. There was a tendency of hemoglobin increasing on the 30–th day of experiment in all experimental groups. The hemoglobin concentration increased by 1.09 times in the 1–st group and in 1,20 times in the 2–nd group. The number of leukocytes was increased in the experimental group. It was also increased by 16.6% in the 1–st group and by 44.4% in the 2–nd group. Phagocytic activity of pseudo eosinophils increased in all experimental groups on the 30–th day of the feed additives using. The most important increasing by 7.2% was in the 2–nd group. There was also a tendency of the phagocytic index increasing in all experimental groups of chicks on the 30–th day of this investigation. It was established that the using of acidulent and PKB probiotic preparation of food at feeding broilers improves hemoglobin levels. It also promotes to leukocytosis, phagocytic pseudo eosinophils activity and improves the overall condition and immunological reactivity.

Improvement of hemoglobin levels after a switch from intravenous to subcutaneous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy.

Intravenous immunoglobulin (IVIG) is recommended treatment for chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). Recent studies have demonstrated that subcutaneous immunoglobulin (SCIG) is feasible, safe, and effective in both disorders. IVIG leads to transient hemolysis and, consequently, we hypothesized that frequent small doses of SCIG exerts less hemolytic activity than a few larger doses of IVIG. In an open-label study, 23 three patients treated with IVIG for CIDP or MMN were switched to SCIG at an equal dosage. IVIG was administered two to three times for 6 weeks. Two weeks after the last IVIG infusion at Week 8, SCIG was initiated with injections twice or thrice weekly until Week 20. Blood samples were drawn 2weeks after IVIG at Weeks 2 and 8 and during SCIG at Weeks 14 and 20 determining hemoglobin (Hb) and hemolytic variables. Seventeen patients completed the study. At enrollment, the Hb level was 138±12 g/L, haptoglobin level was 1.4±0.5 g/L, reticulocyte count was 58.7×109 ± 21.3×109 /L, and bilirubin level was 6.6±2.3 µmol/L. The average of the two blood samples drawn at comparable intervals during IVIG and SCIG showed that Hb increased from 135±15 to 138±15 g/L (p=0.03). During IVIG the hemolytic variables showed signs of mild hemolysis that improved during SCIG, haptoglobin increasing from 1.2±0.5 to 1.5±0.6 g/L (p=0.002), reticulocytes decreasing from 71.9×109 ±35.8×109 to 54.5×109 ±16.3×109 /L (p=0.02), and bilirubin decreasing from 7.3±2.8 to 5.8±1.8 µmol/L (p=0.001). A switch from IVIG to SCIG was associated with a slight increase of Hb levels and an improvement of laboratory variables related to hemolytic activity.

Iron and vitamin D deficiency in inflammatory bowel disease.

Iron and vitamin D deficiency in inflammatory bowel disease.

Ferric maltol in iron deficiency anaemia in patients with inflammatory bowel disease: a guide to its use

Ferric maltol (Feraccru®) is an option for the oral treatment of iron deficiency anaemia (IDA) in patients with inflammatory bowel disease (IBD). In the ferric maltol complex, iron is stabilized in the ferric form (thereby minimizing the potential for mucosal toxicity), while also making the iron highly available for absorption (allowing relatively low dosages of elemental iron to be administered). In patients with IDA associated with IBD who were unable take oral ferrous iron, oral ferric maltol 30 mg twice daily rapidly improved haemoglobin levels and other anaemia-related parameters. It is generally well tolerated, with treatment-related adverse events being mild to moderate in severity and gastrointestinal in nature.

Oral vitamin C supplementation reduces erythropoietin requirement in hemodialysis patients with functional iron deficiency.

Functional iron deficiency (FID) is a major cause of persistent anemia in dialysis patients and also contributes to a suboptimal response to erythropoietin (Epo) administration. Vitamin C acts as an enzyme cofactor and enhances mobilization of the ferrous form of iron to transferrin thus increasing its bioavailability. High-dose intravenous vitamin C has been shown to decrease the Epo requirement and improve hemoglobin levels in previous studies. This study assessed the effect of low-dose oral vitamin C on possible reduction in Epo dose requirements in stable hemodialysis patients with FID. This prospective study included 22 stable hemodialysis patients with FID defined as transferrin saturation (T sat) <30% and ferritin levels of >100mcg/L with Epo requirement of ≥4000U/HD session. Patients received oral vitamin C 250mg daily for 3months. Hemoglobin, iron and T sat levels were recorded monthly. No one received iron supplementation during the study period. There was a significant reduction in median Epo dose requirement in the 15 patients who completed the study, from 203.1U/kg/week (95%CI 188.4-270.6) to 172.8U/kg/week (95%CI 160.2-214.8), (P=0.01). In the seven responders, there was 33% reduction in Epo dose from their baseline. Despite adjustment of Epo dose, the mean hemoglobin level was significantly increased from 10.1±0.6 to 10.7±0.6mg/dL (P=0.03). No adverse effects of oral vitamin C were observed. Daily low-dose oral vitamin C supplementation reduced Epo dose requirements in hemodialysis patients with FID. Limitations of this study include a small sample size and the lack of measurements of vitamin C and oxalate levels. Despite concerns regarding oral vitamin C absorption in dialysis patients, this study indicates vitamin C was well tolerated by all participants without reported adverse effect.

Effect of micronutrient powder supplementation for two and four months on hemoglobin level of children 6–23 months old in a slum in Dhaka: a community based observational study

Anemia is pervasive among children under the age of two years in Bangladesh. This study aimed to assess the effect of daily supplementation of multiple micronutrient powder (MNP) for 2 months and 4 months primarily on hemoglobin status of children aged 6–23 months living in a slum of Dhaka, Bangladesh. It was a community-based observational study where a total of 402 children and 578 children were enrolled for 2 months and 4 months MNP supplementation respectively. Venous blood was collected at enrollment and 5 months later. Hemoglobin level was measured and morbidity episodes recorded from twice weekly home visits. At enrollment, hemoglobin levels were 10.57 ± 1.28 g/dl and 10.78 ± 1.35 g/dl across 2 months and 4 months MNP supplementation groups respectively, compared to 10.65 ± 1.36 g/dl and 11.14 ± 1.11 g/dl at the end-line after MNP supplementation. Plasma hemoglobin increased only after 4 months supplementation in difference-in-difference analysis and this was significantly more in younger children after adjusting the confounding variables (p = 0.03). Prevalence of anemia had improved for both at 2 months (p = 0.015) and 4 months (p = 0.004) of MNP supplementation. Incidence rate ratios (IRR) for diarrhea, cough and fever were comparable across the groups during the supplementation periods and IRR for acute lower respiratory tract infection was significantly lower in 4 months supplementation group with a IRR of 0.30 (95 % CI; 0.22, 0.42). Four months MNP supplementation was relatively more effective in improving hemoglobin level in children 6–24 months.

An Observational Study of Umbilical Cord Clamping and Care Practices during Home Deliveries in Central Uganda

Delayed umbilical cord clamping and care practices have important implications for infant iron stores and neonatal survival. This is especially important in countries like Uganda, where there is a high prevalence of anemia in women and children coupled with a high newborn mortality rate. This study assesses cord clamping and care practices in home births in a coverage area of 12 health centers in 4 districts near Kampala, Uganda. We interviewed 147 women, most of who had at least primary school education and delivered their babies in the homes of traditional birth attendants. Only 65% of the persons conducting delivery washed hands, and most wore gloves. Most frequent cord ties were threads (86.7%), and glove rims (8.3%). Cords were cut with clean instruments in most (93.1%) deliveries. During cord clamping, newborn was positioned at a higher level than mother in 59%, delayed clamping (≥3mins) was reported in 52%. Combination of delayed clamping and positioning of newborn at mother’s level or lower was reported in only 19%. Substances used for cord care included surgical spirit (42.4%), local herbs (24.5%), powder (22.6%), ash (21.6%), saline water (10.3%), and tea (2.8%). Cord care instructions given most commonly were: cleaning with warm saline water (27%), spirit or antiseptics (25%), and herb application (7%). Awareness regarding cord infections was poor (20%). Mother’s education level, and age were not associated with cord clamping or care practices. Our study indicates scope for interventions to help improve hemoglobin levels in infancy. Education regarding cord care practices may reduce infections.

Pegylated interferon for the treatment of early myelofibrosis: correlation of serial laboratory studies with response to therapy.

Pegylated interferon α-2a (Peg-IFN) has been shown to induce hematologic and molecular responses in patients with the Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV) and essential thrombocythemia (ET). We describe a series of patients with long-standing MPNs among whom Peg-IFN was initiated when they developed anemia and increased bone marrow reticulin fibrosis suggestive of early transformation to post-ET (PET) or post-PV (PPV) myelofibrosis (MF). Six patients were treated with Peg-IFN for a mean duration of 33.8 months (range 2-63 months). Five patients had long-standing ET (three were calreticulin (CALR)-positive, one janus kinase 2 (JAK2)-positive, and one JAK2-negative and CALR-negative), and one had long-standing JAK2-positive PV prior to starting Peg-IFN. This is the first study to report that, concurrent with the improvement in anemia, serial laboratory studies demonstrate an increase in serum LDH and left-shifted myeloid cells in the peripheral circulation over approximately 6 months, followed by a gradual normalization of these findings. Splenomegaly also increased and then resolved among responding patients. Serial bone marrow biopsies were available, which showed little change except for improvement in the grade of reticulin fibrosis in two patients. Among patients with early transformation to PET or PPV MF, our data support the efficacy of Peg-IFN in improving hemoglobin levels and reducing splenomegaly. These peripheral blood findings should not, therefore, be considered evidence of treatment failure within the first year of Peg-IFN therapy.

Long-acting somatostatin analogues provide significant beneficial effect in patients with refractory small bowel angiodysplasia: Results from a proof of concept open label mono-centre trial.

Small bowel angiodysplasias account for over 50% of causes of small bowel bleeding and carry a worse prognosis than lesions located elsewhere in the gastrointestinal tract. Re-bleeding rates are high even after first-line endoscopic therapy and are associated with high levels of morbidity for affected patients. Small trials of long-acting somatostatin analogues have shown promising results but have not yet been assessed in patients with refractory small bowel disease. The purpose of this study was to assess the effect of long-acting somatostatin analogues in reducing re-bleeding rates and transfusion requirements, and improving haemoglobin levels in patients with refractory small bowel angiodysplasia. Patients with refractory small bowel angiodysplasia were treated with 20 mg of long-acting octreotide for a minimum of three months. Response was assessed according to: rates of re-bleeding, haemoglobin levels, transfusion requirements, and side effects. A total of 24 patients were initially treated and 20 received at least three doses. Rates of complete, partial and non-response were 70%, 20% and 10% respectively. Average haemoglobin rates increased from 9.19 g/dl to 11.35 g/dl (p = 0.0027, 95% confidence interval (CI) -3.5 to -1.1) in the group overall and 70% remained transfusion-free after a mean treatment duration of 8.8 months. The rate of adverse events was higher than previously reported at 30%. Long-acting somatostatin analogues offer a therapeutic advantage in a significant proportion of patients with small bowel angiodysplasia. With careful patient selection and close observation, a long-acting somatostatin analogue should be considered in all patients with persistent anaemia attributable to refractory disease in conjunction with other standard treatments.

Anemia Due to Inflammation in an Anti-Coagulated Patient with Blue Rubber Bleb Nevus Syndrome

Blue rubber bleb nevus syndrome (BRBNS) is a rare disease characterized by vascular malformations mostly involving skin and gastrointestinal tract. This disease is often associated with sideropenic anemia and occult bleeding. We report the case of chronic severe anemia in an old patient under oral anticoagulation treatment for chronic atrial fibrillation. At admission, the patient also presented fever and increased laboratory parameters of systemic inflammation (ferritin 308 mcg/L, C-reactive protein (CRP) 244 mg/L). A small bluish-colored lesion over the left ear lobe was observed. Fecal occult blood test was negative as well as other signs of active bleeding. Lower gastrointestinal endoscopy revealed internal hemorrhoids and multiple teleangiectasias that were treated with argon plasma coagulation. Videocapsule endoscopy demonstrated multiple bluish nodular lesions in the small intestine. Unexpectedly, chronic severe anemia due to systemic inflammation was diagnosed in an old anticoagulated patient with BRNBS. The patient was treated with blood transfusions, hydration, antibiotic treatment, and long-acting octreotide acetate, without stopping warfarin. Fever and inflammation disappeared without any acute gastrointestinal bleeding and improvement of hemoglobin levels at three-month follow up. This is the oldest patient presenting with chronic anemia, in which BRNBS was also diagnosed. Surprisingly, anemia was mainly caused by systemic inflammation instead of chronic gastrointestinal bleeding. However, we would recommend investigating this disease also in old subjects with mild signs and symptoms.

Iron Deficiency Is Common During Remission in Children With Inflammatory Bowel Disease.

The aim was to study prevalence of iron deficiency in children with inflammatory bowel disease (IBD) during remission. In addition, there was an observational evaluation of hematological response to oral iron. A population-based retrospective study including 90 Swedish children (median 13 years) with IBD was performed. Patient records covered in median 25 months. Iron deficiency was present in 70/77 children (91%) in which iron status could be assessed. In clinical and biochemical remission, iron deficiency was found in 57/67 (85%) of children, and 23 (34%) of them had iron deficiency anemia. Thirty-six iron-deficient children were prescribed oral iron supplementation and 32 (89%) improved hemoglobin levels over 6 months. In conclusion, iron deficiency is common during clinical remission in children with IBD, even in cohorts with low prevalence of anemia. Therefore, regular biochemical screening for iron deficiency is warranted during all stages of disease, irrespective of symptoms and inflammatory blood markers.

Impact of weekly iron folic acid supplementation with and without vitamin B12 on anaemic adolescent girls: a randomised clinical trial.

In India, approx. 70% of the adolescent girls are anaemic (haemolgobin <120 g/l). The present study was a supervised randomised double-blind clinical trial conducted among adolescent girls (11-18 years) to assess and compare the impact of weekly iron folic acid (IFA) supplementation with or without vitamin B12 on reduction in the prevalence of anaemia and on blood/serum levels of haemoglobin, serum ferritin, folic acid and vitamin B12. Community-based randomized controlled trial was carried out in Kirti Nagar slums of West Delhi. A total of 446 mild (100-119 g/l) and moderate (70-99 g/l) anaemic volunteer adolescent girls were identified and randomised into two groups. Weekly supervised supplementation was given for 26 weeks: Group A (n=222): iron (100 mg), folic acid (500 mcg) and placebo; Group B (n=224): iron (100 mg), folic acid (500 mcg) and cyanocobalamin (500 mcg for 6 weeks and 15 mcg for 20 weeks). Haemoglobin, serum ferritin, folic acid and vitamin B12 levels were assessed at baseline and after intervention. A total of 373 subjects completed 26 weeks of supplementation successfully. The mean haemoglobin increased from 106.7±11.2 g/l and 108.9±8.91 g/l in Group A and Group B at baseline to 116.4±10.8 g/l (P<0.001) and 116.5±10.26 g/l (P<0.001) at post-intervention, respectively, with the reduction in the prevalence of anaemia by 35.9% in Group A and 39.7% in Group B (P>0.05). A total of 63.3% participants had deficient vitamin B12 levels (<203 pg/ml) at baseline, which reduced to 40.4% after intervention with cyanocobalamin, whereas no change was observed in vitamin B12 status in the other group. Significant reduction (P=0.01) in the prevalence of serum ferritin deficiency (<15 ng/ml) was observed in the group supplemented with vitamin B12 (from 36.5 to 6.4%) as compared with the other group supplemented with only IFA (from 39.1 to 15.2%). IFA supplementation with or without vitamin B12 is an effective measure to cure anaemia. Although addition of vitamin B12 had similar impact on improving haemoglobin status as IFA alone, it resulted in better ferritin status. Hence, more multi-centre studies with a longer duration of supplementation or higher dose of vitamin B12 may be undertaken to assess the possible impact of vitamin B12 on improving haemoglobin levels in the population.

Hydroxyurea Effectiveness in Children and Adolescents with Sickle Cell Anemia: A Large Retrospective, Population-Based Cohort Study

Background: The clinical efficacy of hydroxyurea (HU) in patients with sickle cell anemia (SCA) is well established. In clinical trials, HU has been demonstrated to alter the clinical course of SCA; HU decreases rates of pain, dactylitis, acute chest syndrome (ACS), transfusions, hospitalizations and improves hemoglobin levels. Other studies have shown that HU improves quality of life and decreases mortality. While evidence of efficacy has been well demonstrated, published data about clinical effectiveness is limited. Additionally, attempts to compare outcomes of patients taking HU to those not taking HU have been limited by the inherent selection bias for greater disease severity in patients on HU. We sought to examine the clinical effectiveness of HU in the large population of patients with sickle cell disease (SCD) at Children's Healthcare of Atlanta (CHOA). The program provides comprehensive care to >1,700 active patients; because they include about 95% of all children and adolescents with SCD in the greater Atlanta Metropolitan Area, the program provides a population-based sample. Currently 57% of the 922 children ≥ 1 yr of age with SCA (SS and Sβ0 thalassemia) who are not on chronic transfusions are receiving HU.Methods: Using a retrospective cohort, pre-post treatment study design to control for disease severity selection bias we evaluated the clinical effectiveness of HU in patients with SCA who received care at CHOA and who first initiated HU in 2009-2011. Children on chronic transfusions, or children with inadequate follow up data and/or who ever took HU in the 3 years prior were excluded. Clinical guidelines for dosing HU have been standardized locally and recommend initial dosage of 20mg/kg/day, followed by dose escalation every 2 months to maximum tolerated dose. For each patient, healthcare utilization, laboratory values and clinical outcomes for the 2-year period prior to HU initiation were compared to those for two years after initiation. Medians were compared using the Wilcoxon Signed Rank test and means using T test. Rate ratios were computed using unadjusted Poisson regression. Interactions testing whether the effect of HU varied by age, sex, or insurance status, were assessed using multivariable Poisson regression.Results: Of 211 children with SCA who initiated HU in 2009-2011, 134 met eligibility criteria. After initiation of HU, the rate of hospitalization was 0.53 the rate before HU, a 47% reduction (Table). The number of inpatient days, emergency room (ER) visits, pain encounters, episodes of acute chest syndrome (ACS), and transfusions were also significantly reduced (Table). The hemoglobin level (mean +/- SD) pre- and post-HU initiation was 7.3+/-2.7 g /dl and 8.1+/- 2.9 respectively; an increase of 0.8+/-1.1, p<0.0001. Similarly, pre-HU mean corpuscular volume increased from 82.9+/-7.5 fl pre-HU to 95.7+/-10.7 post-HU; an increase of 12.8+/-7.2, p <0.0001. There was a statistically significant interaction between the effect of HU and age of initiation of the drug on hospitalization rates; patients < 7 years of age had a greater reduction in hospitalizations than older children (58% vs 33%, p=0.03). The effect of HU on hospitalizations did not vary by sex or insurance type.Table 1Effect of HU initiation on clinical outcomes using Poisson RegressionRate Ratio (Confidence Limits)P ValueHospitalizations0.53 (0.43 - 0.66)<0.0001Inpatient Days0.50 (0.40 - 0.63)<0.0001ER visits0.57 (0.49 - 0.67)<0.0001Pain Encounters0.64 (0.51 - 0.81)0.0001ACS0.57 (0.39 - 0.83)0.0036Blood Exposure0.43 (0.29 - 0.64)<0.0001Conclusions: HU is clinically effective in children and adolescents with SCA. HU decreased hospitalizations, ER visits, pain encounters, ACS, use of transfusions and improved hemoglobin levels. HU effectiveness was similar across gender, insurance types and age, although there was a slightly greater reduction in hospitalizations in younger patients. These results are important as they parallel results obtained from HU efficacy studies, thus demonstrating that in 'real life' settings, even without the additional monitoring and adherence incentives of clinical trials, HU improves short-term outcomes in pediatric SCA. DisclosuresOff Label Use: Hydroxyurea use as disease modifying therapy in pediatric patients with sickle cell disease.

Iron Deficiency Anemia Is Common in Patients Receiving Chemotherapy

Background: Iron metabolism is impaired in patients with cancer and actively receiving chemotherapy. Patients with cancer on active chemotherapy suffer with decreased appetite , poor nutrition, mucositis, gastrointestinal mucosal damage, blood loss as well as anemia of chronic disease due to cytokines release such as Tumor Necrosis Factor, Interleukins and histamins.The purpose of this abstract is to show single institution experience with patients actively receiving chemotherapy and admitted for various reasons and found to have anemia and particularly those patients that were admitted for red blood cell transfusion. Retrospective review of three hundred and fifty patients admitted in the last two years 2014-2015 for different reasons while on chemotherapy with anemia or mainly for blood transfusion. 55% females and 45% males. 77% had solid tumors and 23% with hematological malignancies. Median age 70 years. Thirty five percent 35% of solid tumors were of GI malignancies. Seventy five percenct of all patients had low iron saturation, low serum iron with normal to high total Iron Binding Capacity TIBC. Ferritin level was low in 60% of the patients. Ferritin is a phase reactive markers was elevated in 40% of patients. All patients with elevated ferritin were having low iron saturation with low serum iron and low or normal TIBC. Sixty five 65% of patients received blood transfusion. All patients with iron deficency received intravenous elemental iron support to saturate iron stores.In conclusion: Iron deficiency anemia is very common in patient on active chemotherapy. With Intravenous elemental iron supplemet the requirement of less future red blood transfusion and improvement of hemoglobin levels were achieved in most of patients responding to chemotherapy. Need prospective analysis on patients diagnosed with malignancies and start receiving chemotherapy to prove the value of IV iron support and less requirement of red blood cell transfusion. DisclosuresNo relevant conflicts of interest to declare.

Comparable Outcomes with Eculizumab in Paroxysmal Nocturnal Hemoglobinuria Patients with or without Aplastic Anemia in a Prospective Korean PNH Registry

BackgroundParoxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disease characterized by the intravascular lysis of red blood cells. The three major pathophysiological features of the disease-hemolysis, bone marrow failure (BMF) and thrombosis-historically have been managed with blood transfusions, steroids and anticoagulation. For optimum management, the relative contribution of both hemolysis and BMF to the complex anemia of PNH should be determined. Aplastic anemia (AA) is the most frequently associated BMF syndrome in PNH. In recent years, eculizumab, a humanized monoclonal antibody that binds specifically to human complement protein C5 and inhibits the formation of the terminal complement complex, has been used to prevent the hemolysis associated with PNH. The aim of this study is to evaluate clinical outcomes with eculizumab in patients with PNH concomitant with AA (PNH-AA) and without AA (classic PNH) in a Korean PNH population.MethodsThirty-five patients >18 years of age with PNH diagnosed by flow cytometry and treated with eculizumab for ≥6 months were analyzed in the prospective PNH registry study. Patients were categorized into two groups: PNH-AA and classic PNH. Patients with severe AA were excluded from eculizumab treatment. Biochemical indicators of intravascular hemolysis and hematological laboratory values were assessed at least every 6 months after initiation of eculizumab treatment.ResultsThe median age of the study population was 35 years (range, 21-76 years) at eculizumab initiation and the median duration of eculizumab treatment was 28 months (range, 6-31 months). The treatment effect for reducing hemolysis remained consistent after 6 months of follow up. All patients showed a reduction in LDH levels, which was sustained over the course of treatment (median LDH level, 6.7-fold at baseline to 1.0-fold at 6 months), reflecting inhibition of chronic hemolysis. Fourteen patients (40%) had been diagnosed with aplastic anemia in PNH, and 5 of these patients had received immunosuppressive therapy (IST) for AA management. Of these, 2 achieved complete remission (CR) with hematological recovery before eculizumab initiation, whereas 3 had partial response. Of 35 total patients, 12 were classified as having PNH-AA and 23 with classic PNH, including the 2 patients with CR from IST for management of AA. The mean PNH clone did not change significantly after 6 months of follow up in PNH-AA or classic PNH patients (p=0.575 and 0.965, respectively). Patients receiving eculizumab in both groups had significant changes in mean hemoglobin level after 6 months (p=0.028 and p= 0.035, respectively). The mean number of packed RBC units transfused in patients with PNH-AA was significantly reduced, from 7 units during the previous 6 months to 2 units during the first 6 months of eculizumab use (p=0.009). Thereafter, 1.0, 0.8, and 1.6 units per every 6 months were required from month 6‒12, 12‒18, and 18‒24, respectively. In classic PNH patients, transfusion independence was achieved by 57% (13 of 23) within the first 6 months of treatment and 89% by the last 24 months. Eculizumab also resulted in sustained hematological improvement for patients. There were no significant differences in clinical outcomes (ie, LDH and hemoglobin levels, transfusion requirements) with eculizumab between the two groups.ConclusionsClinical outcomes with eculizumab were significantly improved compared with baseline in patients with both PNH-AA and classic PNH. All patients have been followed up without any recurrence of hemolytic events; overall, the population achieved improvement in hemoglobin levels and a significant reduction in frequency of blood transfusions required. Some PNH-AA patients still required transfusion, reflecting in part a production defect of the bone marrow, whereas classic PNH patients became transfusion-independent over time. These results demonstrate that eculizumab has a role in in the management of patients with PNH-AA, similar to that of classic PNH, to inhibit hemolysis and reduce transfusion requirements. DisclosuresJang:Alexion Pharmaceuticals: Research Funding. Kim:Alexion Pharmaceuticals: Research Funding. Jo:Alexion Pharmaceuticals: Research Funding. Lee:Alexion Pharmaceuticals: Research Funding. Choi:Alexion Pharmaceuticals: Research Funding. Kim:Alexion Pharmaceuticals: Research Funding. Won:Alexion Pharmaceuticals: Research Funding. Chung:Alexion Pharmaceuticals: Research Funding. Kim:Celgene: Research Funding; Il-Yang: Research Funding; Alexion Pharmaceuticals: Research Funding; Novartis: Research Funding. Lee:Alexion Pharmaceuticals: Research Funding. Kim:Alexion Pharmaceuticals: Research Funding. Lee:Alexion Pharmaceuticals: Research Funding.

Réplica: efecto de un suplemento nutricional a base de lípidos en los niveles de hemoglobina e indicadores antropométricos de niños de 5 distritos de Huánuco, Perú

Objectives . To determine the effect of consumption of a lipid-based nutrient supplement (LNS) on hemoglobin levels, anemia and anthropometric indicators in children aged six to eleven months old in five districts in the province of Ambo in the region of Huanuco, Peru.A pre-experimental, pre-post study was performed. The study population included children aged six to eleven months old in 19 health facilities in five districts with very high vulnerability to chronic malnutrition in the province of Ambo, Huanuco. Data from 147 children who received the lipid-based nutrient supplement (LNS) from six to eleven months old were obtained.The mean hemoglobin significantly increased by 0.67 g/dL (p<0.05), the proportion of anemia dropped by 27 percentage points (p<0.001) and the mean z score for height/age decreased by 0.12 (p<0.05). No significant differences for z scores of weight/age and weight/height at the end of the study were found. The LNS had an adherence greater than 90%, and less than 10% of children in the study reported discomfort during consumption.LNS supplementation achieved improved hemoglobin levels and reduced the prevalence of anemia in children under twelve months, which might constitute an effective alternative to prevent and control childhood anemia.

The Acute Chest Syndrome in Cameroonian children living with sickle cell disease.

BackgroundAlthough sub-Saharan Africa (SSA) is particularly affected by sickle cell disease (SCD), there is dearth of research on this topic in the region, specifically targeting the magnitude of SCD-related complications. We therefore conducted this study to determine the burden of acute chest syndrome (ACS) and describe its clinical and therapeutic aspects among SCD children in Cameroon, a SSA country.MethodsThis was a retrospective study carried-out from September 2013 to June 2014 at the SCD unit of the Mother and Child Centre of the Chantal Biya Foundation, a pediatric reference centre in Yaoundé, Cameroon. We enrolled all SCD children with confirmed diagnosis of ACS, and recorded their clinical presentation at admission along with their evolution during hospitalization.ResultsTwenty one cases of ACS were identified during the study period, from 338 hospitalizations of children with SCD. Ages ranged from 11 months to 16 years with a mean (standard deviation) of 5.5 (3.4) years, and a male/female sex ratio of 3.2/1. We noticed relatively low levels of HbF, from 6.4 to 21.9 % with a mean of 14.6 % (6.0 %). The three main symptoms at admission were fever (90.5 %), cough (81 %) and chest pains (28.6 %). Two patients (9.5 %) developed ACS 2 days after admission. The mean values of leukocytes, neutrophils, serum CRP, serum LDH and hemoglobin were respectively 32479.4 (17862.3)/mm3, 23476 (11543.7)/mm3, 228.2 (132.6) mg/l, 3452.3 (2916.3) IU/l and 6.5 (1.2) g/dl. The main localizations of radiological alveolar consolidations were the lower lobes (90.5 %). Treatment associated broad-spectrum antibiotics (100 %), hydration (100 %), analgesics (43.2 %), whole blood transfusion (66.7 %), and oxygen supplementation (33.3 %). Blood transfusion significantly improved hemoglobin level (p = 0.039). The duration of hospitalization, the mean of which was 6.8 (3.1) days, was influenced by none of the tested variables (all p values > 0.05).ConclusionACS is frequent among SCD children in our milieu. Its etiologies seem to be multifactorial. Patients’ parents should be educated to recognize early signs and symptoms of the disease, and consult rapidly. Additionally, clinicians must be trained to diagnose ACS, and manage it promptly and efficiently to avoid its related catastrophic consequences.

Preprocedure Anemia Management Decreases Transfusion Rates in Patients Undergoing Transcatheter Aortic Valve Implantation

BackgroundPeriprocedural blood transfusions are associated with long-term mortality in patients undergoing transcatheter aortic valve implantation (TAVI). We sought to assess the impact of a preoperative blood conservation approach in treating anemia and preventing blood transfusions in patients undergoing TAVI. MethodsOur cohort consisted of all patients evaluated in our structural heart clinic between January 1, 2012 and December 31, 2014. From March 2013, all anemic TAVI candidates were referred to the blood conservation clinic (BCC). We evaluated the effectiveness of the program to increase hemoglobin levels and to decrease the blood transfusion rates in the TAVI cohort. A multivariable logistic regression model was used to evaluate the association of being assessed by the BCC with receipt of a blood transfusion. ResultsThe cohort included 239 patients, 62% of whom were anemic. Beginning in March 2013, 60 patients were evaluated in the BCC and treated with intravenous/oral iron or subcutaneous epoetin alfa, or both. Patients who underwent blood conservation had a significant increase in hemoglobin levels from 10.8 ± 1.1 g/dL to 11.8 ± 1.2 g/dL (P < 0.001).Implementation of the BCC was associated with a substantial decrease in the average blood transfusion rate from 33.3% before program initiation to 15.3% after implementation (P < 0.001). After adjusting for baseline hemoglobin values and comorbidities, being assessed at the BCC was strongly associated with a reduction in the need for transfusion (odds ratio, 0.28; 95% confidence interval, 0.11-0.69; P = 0.006). ConclusionsPreprocedural anemia management was successful in improving hemoglobin levels in anemic patients and in decreasing transfusion rates in TAVI.