Severe Hb Research Articles

Retrospective analysis of hemophilia B in Turkey: identifying main characteristics and treatment options

BackgroundHemophilia B (HB), an X-linked recessive inherited bleeding disorder, exhibits a high prevalence among males. ObjectivesTo present the first national cohort of persons with HB to define the demographics, clinical characteristics, and treatment patterns in Turkey. MethodsThis multicenter, retrospective study included 433 alive persons with HB registered in 35 centers between 1961 and 2018. Analyses were performed by age subgroups (0-17 years, 18-64 years, and ≥65 years), disease severity by factor levels (severe, <1 IU/dL; moderate, 1-5 IU/dL; mild, >5 IU/dL). Additionally, patients were stratified based on the initiation year of follow-up at the relevant study center, creating 2 periods: 1993-2006 (referred to as period A) and 2007-2018 (referred to as period B). ResultsPredominantly male (98.6%), the median age at data entry was 22.1 years (n = 429). The majority (49.0%) had moderate HB, followed by severe (30.0%) and mild (15.7%) disease. Of the 377 patients with complete treatment details, 209 (55.4%) were under prophylaxis from their diagnosis onwards, while 79 patients (21.0%) only received on-demand treatment. Additionally, 89 patients (23.6%) initially underwent on-demand treatment and later were switched to prophylaxis. Knees were the primary site of bleeding and the most frequently intervened joints. Most of the major (47.5%) and minor (53.3%) orthopedic procedures were carried out in persons with severe HB, while half of radioactive synovectomy procedures were performed on persons with moderate HB. ConclusionThis paper describes the demographics, clinical characteristics, and treatments patterns of a large cohort of alive persons with HB on a national scale.

Prevalence of anemia in pregnant women attending out-patient clinic: A cross-sectional study

Anemia is a very common condition in pregnancy. It represents one of the most common risk factors for maternal as well as fetal complications. Its early identification, treatment and prevention is necessary to avoid these complications.The objective of this study was to evaluate prevalence of anemia in pregnant women attending outpatient department.In this single center retrospective clinic-based study carried pregnant women attending for their regular ante-natal checkup were included. Demographic details, hemoglobin level and prior obstetric related history was noted. Prevalence of anemia was estimated based on the hemoglobin level. The severity of anemia was categorized as mild (Hb level 10 g/dL to 10.9 g/dL), moderate (Hb level 7 g/dL to 9.99 g/dL), severe (Hb level &amp;#60;7 g/dL).Corelates of anemia were examined based on the demographic parameters. The study included 199 pregnant females with mean (SD) age was 29.6 (4.1) years. Mean (SD) hemoglobin of the study population was 10.6 (1.4) gm. A total of 174 (87.44%) females were house-makers and 165 (82.9%) were from the urban area. Anemia was observed in 76 (38.2%) pregnant females. Mild, moderate and severe anemia was observed in 32 (42.11%), 43 (56.58%) and 1 (1.3%) female respectively. Out of 76 pregnant females with anemia, 66 (86.8%) were housemakers. No significant difference was observed in the mean age (p=0.34) and body weight (p=0.69) of pregnant females with or without anemia. There was no significant difference in the anemia prevalence in rural versus urban pregnant females (p=0.33).Prevalence of anemia in pregnant women was 38.2%. Moderate anemia was more common than mild and severe anemia. There was no significant difference in the mean age or residence of pregnant females with anemia versus without anemia.

Predictive value of hemoglobin decrease for necrotizing enterocolitis in preterm infants with late-onset sepsis

To study the predictive value of hemoglobin (Hb) decrease for the occurrence of necrotizing enterocolitis (NEC) in preterm infants with late-onset sepsis (LOS) . Clinical data of 93 LOS preterm infants were collected for retrospective analysis, among which 16 infants developed NEC while 77 infants did not. Based on the decrease in Hb levels from the most recent Hb measurement before LOS occurrence to the initial Hb levels during LOS, the infants were divided into three groups: no Hb decrease (n=15), mild Hb decrease (Hb decrease <15 g/L; n=35), and severe Hb decrease (Hb decrease ≥15 g/L; n=43). Multivariate logistic regression analysis was conducted to explore the predictive factors for NEC secondary to LOS, and the value of Hb decrease in predicting NEC secondary to LOS was evaluated through receiver operating characteristic curve analysis. The incidence of NEC in the severe Hb decrease group, mild Hb decrease group, and no Hb decrease group were 26%, 14%, and 0% (P<0.05), respectively. Multivariate logistic regression analysis revealed that a larger Hb decrease was an independent predictive factor for NEC in LOS preterm infants (OR=1.141, 95%CI: 1.061-1.277, P<0.001). Receiver operating characteristic curve analysis showed that the area under the curve for predicting NEC in preterm infants with LOS using Hb decrease (with a cut-off value of 20 g/L) was 0.803, with sensitivity and specificity of 0.69 and 0.78, respectively. Hb decrease can serve as an indicator for prediction of NEC in preterm infants with LOS.

TO ASSESS THE ACCURACY AND RELIABILITY OF PALLOR IN THE ORAL CAVITY AND PALPEBRAL CONJUNCTIVA TO CLINICALLY DIAGNOSE ANAEMIA IN MIDDLE AGED FEMALE PATIENTS BY USING HAEMOGLOBIN AS THE REFERENCE STANDARD

Aim: To accurately determine the reliability of pallor on the dorsal surface of tongue and/or palpebral conjunctiva to diagnose anaemia in middle aged female patients, by using haemoglobin as the reference standard. To correlate pallor with different grades of anaemia according to WHO criteria. Objective: A cost effective chair side clinical observation of pallor to diagnose anaemia in middle aged female patients and to provide counselling thereby reducing the prevalence of anaemia and its associated morbidities, especially in poor resource setting. Method: Between 1st June 2022 to 30th Aug 2022, all female dental outpatients between 40-65 years of age were prospectively examined. Among these subjects,100 female patients with pallor on the dorsal surface of tongue and/or palpebral conjunctiva who met the specified inclusion and exclusion criteria, provided informed consent, and who had undergone blood test within one day of clinical pallor detection were enrolled in the study. Based on haemoglobin levels, anaemia was divided into mild, moderate, and severe according to WHO criterion (Hb: &lt;12g/dl). Anaemia was divided into mild (Hb: 11-11.99 g/dl), moderate (Hb: 7-10.99 g/dl), and severe (Hb: &lt; 7g/dl). Data was expressed as frequency and percentages. Result: In the present study, 82% of subjects with either conjunctival pallor or tongue pallor or both were anaemic with laboratory proven haemoglobin levels &lt; 12 g/dl which was found to be statistically significant. 14.6% subjects were diagnosed with mild anaemia, 51.2% with moderate anaemia, and 34.1% with severe anaemia. Among patients with mild and moderate anaemia, conjunctival pallor out performed tongue pallor whereas in subjects with severe anaemia, tongue pallor outperformed conjunctival pallor. Detecting pallor in a female patient is a dependable sign of anaemia. Furthermore, identifying tongue surface pallor is a strong signal of severe anaemia in female patients whereas conjunctival pallor is a good indicator for mild and moderate anaemia. The effective implementation of dietary counselling has the potential to significantly reduce the prevalence of anaemia.

Management of Delayed Hemolytic Transfusion Reaction in a Patient with Sickle Cell Disease: A Case Report

Background: Sickle cell disease (SCD) is a group of inherited blood disorders characterized by abnormalities in hemoglobin (Hb), leading to distortion in shape of red blood cells (RBCs) and their breakdown, potentially blocking blood flow and resulting in pain and anemia. This can significantly impact the patient’s quality of life. Patients often require multiple blood transfusions to prevent complications associated with SCD by reducing the concentration of damaged hemoglobin. However, one of the significant complications of blood transfusions is Delayed Hemolytic Transfusion Reaction (DHTR), which occurs due to RBC alloimmunization (i.e., formation of antibodies against donor RBC antigens). DHTR can manifest as a sudden decrease in hemoglobin levels, which may progress to rapid multiorgan failure and death. Thus, prompt diagnosis is crucial for timely management. This case report highlights the diagnosis and management of a 56-year-old African American female with SCD who presented with bilateral severe knee pain and low Hb levels. Case Presentation: The patient’s symptoms, past medical history, and investigation findings led to a diagnosis of DHTR. Management was conducted within the framework of Bloodless Medicine, incorporating strategies to minimize blood loss and optimize erythropoiesis. Treatment included the use of erythropoietin (EPO) to manage hemoglobin levels and the administration of opioids and supplemental oxygen for symptom relief. Conclusion: Our case report highlights the challenges and various management strategies employed in treating DHTR in SCD patients. It emphasizes the importance of early recognition of the complication and compares the risks and benefits of additional blood transfusions in such patients. By presenting this case, we aim to contribute to the growing literature on DHTR in SCD patients and highlight the need for further research and optimized management strategies in this population.

The current challenges faced by people with hemophilia B.

Hemophilia B (HB) is a rare, hereditary disease caused by a defect in the gene encoding factor IX (FIX) and leads to varying degrees of coagulation deficiency. The prevailing treatment for people with HB (PWHB) is FIX replacement product. The advent of recombinant coagulation products ushered in a new era of safety, efficacy, and improved availability compared with plasma-derived products. For people with severe HB, lifelong prophylaxis with a FIX replacement product is standard of care. Development of extended half-life FIX replacement products has allowed for advancements in the care of these PWHB. Nonetheless, lifelong need for periodic dosing and complex surveillance protocols pose substantive challenges in terms of access, adherence, and healthcare resource utilization. Further, some PWHB on prophylactic regimens continue to experience breakthrough bleeds and joint damage, and subpopulations of PWHB, including women, those with mild-to-moderate HB, and those with inhibitors to FIX, experience additional unique difficulties. This review summarizes the current challenges faced by PWHB, including the unique subpopulations; identifying the need for improved awareness, personalized care strategies, and new therapeutic options for severe HB, which may provide future solutions for some of the remaining unmet needs of PWHB.

Proactive Systematic Hemophilia Carrier Screening: A Step Towards Gender Equity in Hemophilia Care

Introduction Despite multiple awareness-raising initiatives, and in contrast with male persons with hemophilia (PwH), a considerable number of carriers and female PwH still go undiagnosed. We here present the findings of a proactive and extensive hemophilia carrier screening project. Methods From May 2021 until April 2023, potential and obligate carriers of hemophilia A (HA) and B (HB) were identified by updating family trees of all PwH regularly followed at the Cliniques universitaires Saint-Luc. Data from previously screened female individuals (bleeding history, coagulation factor assays and testing for the index patient's pathological genetic variant) were collected retrospectively through electronic medical records (EMRs). Female individuals who had not been previously screened or with missing data were provided with a total of 125 invitation letters by related index hemophilia patients. The study protocol received approval of the local ethics committee. Results All 287 male PwH (226 HA, 61 HB) from 228 families (180 HA, 48 HB) were included in the analysis. Seven female PwH (3 HA, 4 HB) were considered as index cases in their families. In total, based on the family trees, there were 900 females, among which 454 were obligate and/or genetically proven carriers of hemophilia and 118 were found to be non-carriers (Figure 1). Mean age at diagnosis was 30.7 years (range 1-82) in families with HA and 30.1 years (range 0.5-93) in families with HB, without significant difference between these two groups (p=0.809) or between families with severe, moderate or mild hemophilia (p=0.535). Genetic testing for pathological variants has been conducted in 133 obligate, 237 potential and 4 sporadic carriers, and remains to be performed in 190 obligate and 328 potential carriers. Eight females were obligate non-carriers. The group of mothers, sisters and daughters of PwH comprised 543 females, of which at least 178 (35.7% of those with known date of birth) were of reproductive age (18-49 years). Seventy-three percent of females in the latter group have had genetic testing. The proportion of female individuals genetically tested did not significantly differ between families of different severities of HA (p=0.132). In families with moderate HB, female individuals were more likely to be tested (genetic status known in 59.4%) than in other HB severity groups (p=0.01), yet this may be attributed to the presence of one large family comprising 6 male persons with moderate HB and 22 female individuals, of whom a large proportion (n=18, 82%) has had genetic testing. Among carriers with known coagulation factor levels (261/454), 42 (23.0%) and 23 (29.5%) carriers of HA and HB, respectively, had a factor level below 40 IU/dL, and 65 (35.5 %) and 32 (41.0%) had a factor level below 50 IU/dL. The proportion of carriers with a factor level below 40 IU/dL did not significantly differ between families with severe, moderate and mild hemophilia (22.6%, 34.7% and 22.7% respectively, p=0.213), neither did mean coagulation factor levels in carriers with a factor deficiency in these groups (26.2, 30.4 and 27.1 IU/dL in families with severe, moderate and mild HA and HB, p=0.344). Carriers with a coagulation factor deficiency of less than 40 IU/dL were screened earlier than other female individuals (mean age at diagnosis 25.8 and 31.8 years, respectively, p=0.034). Conclusions This study represents the first reported attempt to systematically identify all (potential) hemophilia carriers within families of all PwH followed at a single hemophilia treatment center. To date, this initiative has allowed 44% of the entire cohort to be screened, and carrier status to be genetically confirmed in 73% of mothers, sisters and daughters of PwH who are of childbearing age, based on the date of birth documented in their EMR. Although original and promising, these data reflect the major challenges and difficulties in reaching out and providing appropriate screening to all women genetically linked to one or more PwH. The carrier screening efforts that have been initiated in our center, and which should ideally be replicated across the hemophilia community globally, appear as a critical step towards providing equal access to haemophilia diagnosis and care to all potentially affected individuals, regardless of their gender.

Donor Hemoglobin Genotype Does Not Impact Outcomes Following Matched Related Donor Hematopoietic Cell Transplantation for Sickle Cell Disease: A STAR Study

Sickle cell disease (SCD) is an inherited hemoglobin (Hb) disorder which leads to significant morbidity and early mortality. Hematopoietic cell transplantation (HCT) is the only curative treatment with long-term outcome data, demonstrating excellent symptom-free survival particularly when a matched related donor (MRD) is available. Most MRD have sickle cell trait (Hb AS), but trait donor HCT is considered acceptable by the FDA and without negative impact. Further, initial gene addition and editing approaches for SCD have resulted in a trait-like status with benefit. Sickle trait, however, is associated with complications such as papillary necrosis, bacteriuria, splenic infarction, and exercise-induced death. The primary aim of this study was to compare long-term outcomes following MRD HCT for SCD based on donor Hb genotype, to objectively describe any impact on outcomes. Retrospective data was available for this analysis on 182 SCD patients ≥1 year post MRD HCT at 10 participating Sickle Transplant Advocacy and Research (STAR) Alliance centers. Summary statistics were presented as mean (standard deviation) for continuous variables and count (%) for categorical variables. Comparisons were made between Hb AA and Hb AS donor groups using both parametric and non-parametric tests for continuous variables and Chi-square test/exact test for categorical variables, with p-value &amp;lt;0.05 set as significant. Amongst 182 patients undergoing MRD HCT, 67% (n=122) had a Hb AS donor ( Table). In the overall cohort, median age at HCT was 8.7 (4.8) years and most patients had HbSS (n=174; 96%) with a severe clinical phenotype (n=97; 54%). HCT was performed using bone marrow (n=166; 92%) with myeloablative conditioning (n=156; 86%) in the majority. Patients with a severe disease phenotype and Hb AS donor were significantly more likely to have recurrent vaso-occlusive pain crises as an indication for HCT (p=0.033), otherwise there were no differences in baseline patient or HCT characteristics between cohorts. With mean post-HCT follow up of 4.5 (3.9) and 5.1 (4.1) years in Hb AA and Hb AS donor cohorts (p=0.145), no significant differences were seen in recipient outcomes including time to neutrophil and platelet engraftment, number of or time to last platelet transfusion, myeloid or unsorted % donor chimerism, number with acute (day 100) or chronic GVHD (1 year), or time to discontinue immunosuppression (data not shown). Disease recurrence and need for 2 nd HCT were rare in both cohorts (AA: 2 [3%] and 2 [3%]; AS: 3 [3%] and 4 [3%]; p=0.665 and 1.0, respectively). Two (3%) and 5 (4%) patients died in the AA and AS cohorts, respectively (p=1.0). Aside from a statistically (but not clinically) significant difference in Hb at day 30 (p=0.044), no difference was seen in longitudinal Hb or markers of hemolysis (LDH and ARC; Figure). No significant difference was seen in median number of RBC units transfused (AA: 4.0 [2.0-6.0]; AS: 3.0 [2.0-6.0]; p=0.454) or days to last transfusion (AA: 23.0 [14.0-77.0]; AS: 22.0 [13.0-75.0]; p=0.86). SCD complications were rare post-HCT, with no difference seen between cohorts in number (%) with VOC (AA: 1 [2%; had 2 separate VOC events]; AS: 3 [3%]; p=1.0), ACS (none reported), chronic pain (AA: 0 [0%]; AS: 1 [&amp;lt;1%]; p=1.0), or other SCD-related complications (AA: 2 [3%]; AS: 9 [7%; had 11 separate other events]; p=0.456). Stroke occurred in a significantly higher proportion with an AA versus AS donor (5 [8%] and 2 [2%], respectively; p=0.04). No significant differences were seen in longitudinal (1 and 2 years and at last follow up) post-HCT cardiac (EF, SF, TRJ velocity), pulmonary (FEV1, FVC, DLCO), or renal (GFR) function between cohorts (data not shown). Our results indicate that in MRD HCT for SCD, AS and AA donors yield comparable long-term outcomes. In this retrospective and registry-based study design, detailed analyses did not show differences between the two cohorts at baseline or at any timepoint post-HCT. While there were some outcome differences between the cohorts, they were either not clinically significant or did not have a scientific rationale, and thus were likely due to chance alone (denoted by bolding in Table). Given the young age of our cohort at HCT and thus a smaller proportion with SCD-related organ dysfunction, our results may not be applicable to an older cohort with significant organ dysfunction which will require a separate analysis.

Protein S antibody as an adjunct therapy for hemophilia B

AbstractHemophilia B (HB) is caused by an inherited deficiency of plasma coagulation factor IX (FIX). Approximately 60% of pediatric patients with HB possess a severe form of FIX deficiency (<1% FIX activity). Treatment typically requires replacement therapy through the administration of FIX. However, exogenous FIX has a limited functional half-life, and the natural anticoagulant protein S (PS) inhibits activated FIX (FIXa). PS ultimately limits thrombin formation, which limits plasma coagulation. This regulation of FIXa activity by PS led us to test whether inhibiting PS would extend the functional half-life of FIX and thereby prolong FIX-based HB therapy. We assayed clotting times and thrombin generation to measure the efficacy of a PS antibody for increasing FIX activity in commercially obtained plasma and plasma from pediatric patients with HB. We included 11 pediatric patients who lacked additional comorbidities and coagulopathies. In vivo, we assessed thrombus formation in HB mice in the presence of the FIXa ± PS antibody. We found an accelerated rate of clotting in the presence of PS antibody. Similarly, the peak thrombin formed was significantly greater in the presence of the PS antibody, even in plasma from patients with severe HB. Furthermore, HB mice injected with PS antibody and FIX had a 4.5-fold higher accumulation of fibrin at the thrombus induction site compared with mice injected with FIX alone. Our findings imply that a PS antibody would be a valuable adjunct to increase the effectiveness of FIX replacement therapy in pediatric patients who have mild, moderate, and severe HB.

MDS-Related Anemia Is Associated with Impaired Quality of Life but Improvement Is Not Always Achieved by Increased Hemoglobin Level.

Quality of life is impaired in MDS, but the role of hemoglobin level is unclear. To study the Hb-QoL correlation at diagnosis and 1 year later, patients filled out the EQ-5D questionnaire, assessing their mobility, self care, daily activities, pain/discomfort, and anxiety/depression, using scores of 0 (normal), 1 (mild/moderate), or 2 (poor). They also evaluated their health using a visual analogue scale, scoring from 0 (poor) to 100 (excellent). The anemia subgroups were: none/normal (Hb ≥ 12.5 g/dL), mild (10 ≤ Hb < 12.5), moderate (9 ≤ Hb < 10), severe (8 ≤ Hb < 9), or very severe (Hb < 8). LR-MDS patients (n = 127) and inpatient controls (n = 141) participated. The anemic patients had a poor QoL and the MDS patients had a lower QoL with a lower Hb. The controls had no QoL difference among the various anemia subgroups. In addition, the MDS QoL sharply decreased with an Hb of < 9. The MDS patients showed a wide QoL variability, i.e., different QoL scores in the same Hb subgroup, suggesting that other factors affect QoL (e.g., age and comorbidities). After 1 year (n = 61), the QoL was still poor for most MDS patients (including 27 patients with an increased Hb). In summary: (1) a poor QoL in MDS-anemia is non-linear, suggesting other influencing factors on QoL. (2) The sharp QoL drop with Hb < 9 g/dL challenges the transfusion Hb threshold. (3) The QoL in anemic MDS patients might differ from that in non-MDS patients. (4) Raising Hb, while recommended, does not guarantee an improved QoL.

In vivo intranasal delivery of coagulation factor IX: a proof-of-concept study

BackgroundHemophilia B (HB) is a bleeding disorder characterized by coagulation factor (F) IX (FIX) deficiency. The current standard-of-care for severe HB is prophylaxis with long-term repetitive intravenous (i.v.) infusions of recombinant FIX (rFIX) with standard half-life or extended half-life. Unmet needs remain regarding the development of non-invasive administration routes for coagulation factors. The aim of this study was to evaluate the effectiveness of intranasal delivery (IND) of rFIX and rFIX fused to Fc fragment (rFIX-Fc) in mice. MethodsDrops of rFIX and rFIX-Fc were deposited in the nostrils of wild-type, FcRn knock-out, FcRn humanized, and FIX knock-out mice. rFIX mucosal uptake was evaluated by measuring plasma FIX antigen and FIX activity (FIX:C) levels, and by performing histologic analysis of the nasal mucosa following IND. ResultsAfter IND, both rFIX and rFIX-Fc were equally delivered to the blood compartment, irrespective of the mouse strain studied, mostly through a passive mechanism of transportation across the mucosal barrier, independent of FcRn receptor. Both plasma FIX antigen and FIX:C activity levels increased following IND in FIX knock-out mice. ConclusionThis proof-of-concept study describes evidence supporting the nasal route as an alternative to FIX i.v. infusion for the treatment of HB.

Impact of Preoperative Anemia on Hospitalization, Death, and Overall Survival in Patients With Peripheral Artery Disease Undergoing Endovascular Therapy: A Retrospective Cohort Study in the United States and Canada

Purpose: Preoperative anemia is associated with adverse outcomes after cardiac and noncardiac surgeries, but outcomes after an endovascular peripheral vascular intervention (PVI) are not well established. We aimed to assess the association of preoperative anemia with 30 day death, hospital length of stay (LOS), and overall (long term) survival in patients undergoing an endovascular PVI for peripheral artery disease. Materials and Methods: In this retrospective, cohort study in the United States and Canada, we queried the national Vascular Quality Initiative database for all endovascular PVIs performed between 2010 and 2019, and outcomes were correlated with patients’ hemoglobin (Hb) levels. Anemia was classified as mild (Hb=10–13 g/dL for men and 10–12 g/dL for women), moderate (Hb=8–9.9 g/dL), and severe (Hb<8 g/dL). Results: A total of 79 707 adult patients who met study criteria underwent endovascular PVI. The mean age was 68 years, and 59% of patients were male. Anemia was documented in 38 543 patients (48%) and was mild in 27 435 (71%), moderate in 9783 (25%), and severe in 1325 (4%). The median follow-up duration was 4 years (range, 1.25–5.78 years). On univariate analysis, 30 day mortality, total LOS, and overall survival were significantly associated with the level of preoperative anemia. These associations persisted in the multivariate models. Kaplan-Meier survival analysis demonstrated an association of death with degree of anemia (p<0.001). Conclusion: The presence and degree of preoperative anemia were independently associated with increased 30 day mortality and LOS and decreased overall survival for patients with peripheral artery disease who had undergone endovascular PVI. Clinical Impact: The findings from this study have many implications for how to approach vascular surgery in patients with variable hemoglobin levels. Our findings will strengthen our ability to conduct accurate preoperative risk stratification for patients undergoing peripheral vascular interventions. This may also mitigate healthcare expenditures if findings are applied in a way that can lower patient length of postoperative stay while also maintaining quality of care and patient safety. Our results will also serve as guidance for clinical trials, and future prospective trials should evaluate the effect of preoperative optimization of hemoglobin as a potentially modifiable risk factor for outcomes.

A synchronized approach between Emergency Department and Anemia Clinic to intravenous iron treatment for very severe (Hb

A synchronized approach between Emergency Department and Anemia Clinic to intravenous iron treatment for very severe (Hb <7.0 g/dL) and extreme (<5.0 g/dL) iron-deficiency anemia: short-, medium- and long-term efficacy and safety analysis.

Predictors of Anemia Among Pregnant Women Attending Public Healthcare Facilities in Bengaluru, South India

Background and Aims Anemia in pregnancy leads to poor outcomes. The Indian government has reduced anemia only at a marginal level from 58 in the National Family Health Survey NFHS-3 to 50.4 in the NFHS-4 survey. This study aims to determine the predictors of anemia among pregnant women in the maternal antecedents of adiposity and studying the transgenerational role of hyperglycemia and insulin MAASTHI cohort of Bengaluru. This will help provide valuable information to design the appropriate intervention to lower the prevalence of anemia.Method The study was nested in the MAASTHI cohort study in public health facilities in Bengaluru. The present study was a multi-center prospective cohort study. Pregnant women attending health facilities for antenatal care were included in the study after obtaining their written consent. Socio-demographic information obstetric details smoking status and alcohol consumption among participant and their spouse were noted. Social support psychosocial stress and detailed anthropometry were recorded. All eligible pregnant women were asked to undergo a blood hemoglobin and oral glucose tolerance test after the completion of 26 weeks of gestation.Results A total of 2447 study participants with a mean age of 24.28 plusmn 4.07 years were included in the study. The overall prevalence of maternal anemia was 44.4 N 1375. Among them 24 had mild Hb 10ndash10.9 gmdl 15.8 had moderate Hb 7-9.9gmdl and 0.4 had severe anemia Hb lt7gmdl. Multivariate analysis showed that obstetric factors such as parity had a significant association with anemia. In contrast nutrition-related factors such as not consuming iron and folic acid IFA supplements and being underweight were positively associated with anemia.Conclusion Our study found a higher prevalence of maternal anemia during pregnancy in urban Bengaluru. The government should take proactive health promotion initiatives such as effective campaigns and nutrition-specific interventions especially iron supplementation. Integrated dietary interventions such as food fortification with iron and folate and IFA supplementation targeting from childhood to adolescence and reproductive age rather than targeting pregnant women may help to reduce the burden of anemia.

Anemia in children aged 6 to 59 months attending a quaternary health facility in Maputo, Mozambique

Abstract Background Globally, anemia prevails as a public health issue, being also a concern in Mozambique, where about two-thirds of children 6-59 months of age are affected by anemia. We carried out this study to estimate anemia prevalence and evaluate structural determinants and hematological parameters association among children aged 6 to 59 months attending pediatric inpatient and outpatient services in a Quaternary Health Facility in Maputo City Province, Mozambique. Methods From August 2021 to January 2022, we conducted a cross-sectional study at the ‘Maputo Central Hospital’ where we collected data from 397 inpatients or outpatients who attended pediatric consultations. The cut-off values for anemia were: mild (10g/dL≤Hb≤10.9g/dL), moderate (7g/dL≤Hb≤9.9g/dL), severe (Hb &amp;lt; 7.0g/dL). We used SPSS 28.0 software to perform descriptive analyses and Chi-Square tests. Results Our preliminary findings show that the total rate of positive cases was 30.0% moderate anemia (119/397), 23.9% mild anemia (95/397), and 7.3% severe anemia (29/397). Anemia frequencies were higher in male patients unregarding the type (54.2% moderate, 62.1% mild, 67.9% severe). Anemia prevalence was higher among children aged 24-59 months (41.2% moderate, 47.4% mild, 51.7% severe; p &amp;lt; 0.05). The rate of all anemia types was higher in children from rural areas and Maputo City province relative to those from urban areas and other country provinces. The level of education of the child's companion to the consultations was associated with anemia (p ≤ 0,05), with higher rates observed in secondary level education. We observed no association between iron or serum ferritin values to anemia. Key messages • Children aged 24-59 months, children from rural areas, and who are male are more vulnerable to suffering anemia than their peers, thus needing more monitoring during their growth. • Nutritional-anemia-specific interventions targeting the first 1000 days of life may be helpful to its reduction in children.

Erratum: A Cross-sectional Analysis of Treatment in PUPs in 2021 in Germany – First Data from the GEPHARD Study Group

Abstract Objectives Initial treatment in patients with haemophilia remains challenging. The choice of therapy, timing, dose and frequency have been and are still under intense debate. New treatment options like novel factor concentrates and non-factor therapies broaden the discussion. Design The German Paediatric Haemophilia Research Database (GEPHARD) is a multicentre prospective observational study including children and adolescents with haemophilia A or B (FVIII or FIX levels &lt;25 IU/dL) in a German treatment centre after January 1st, 2017. A cross-sectional analysis was performed in June 2021. Results 249 children and adolescents from 22 participating centres in Germany were analysed in this cross-sectional analysis. 203 patients suffered from haemophilia A (PwHA) and 46 from haemophilia B (PwHB). The median age at diagnosis for Pw severe HA or HB was 6 or 2 months, the median age at analysis was 33 or 35 months for Pw severe HA or B, respectively. 117 Pw severe HA received treatment, including plasma derived concentrates (n = 43), standard recombinant concentrates (n = 23), extended half live concentrates (n = 33) and non-replacement therapies (n = 18). For Pw severe HB, plasma derived concentrates (n = 3), standard recombinant concentrates (n = 8) and extended half live concentrates (n = 14) were used. Current inhibitors were reported in 16 PwHA and 1 PwHB. Conclusions GEPHARD was successfully established as a national cohort for newly diagnosed PwH in Germany. Epidemiological and treatment data were presented. Longitudinal analyses of this growing cohort will allow to value treatment strategies and their outcome in the evolving treatment landscape.

MANAJEMEN ASUHAN KEBIDANAN INTRANATAL PADA NY “D” DENGAN ANEMIA DI RSIA SITTI KHADIJAH I MUHAMMADIYAH MAKASSAR

Introduction Anemia is a decrease in the haemoglobin. Mild anemia Hb &lt;10 gr/dl, moderate anemia Hb 7-8 gr/dl, and severe anemia Hb &lt;6 gr/dl. WHO announced that anemia was considered to be the major cause of maternal mortality during pregnancy and childbirth delivery The findings of previous research showed that the presentage of maternal mortalitiy during childbirth because of anemia was 70%, while the were only about 19.7% of cases due to other reasons. Therefore, based on the aforementioned problem, it is essential to conduct proper treatment in dealing with high occurrences of anemia in childbirth. The purpose of this study was to investigate and provide internal midwifery care management on a pregnant patient with anemia at RSIA Sitti Khadijah I of Muhammadiyah Makassar. Method The Research was conducted in accordance with health and midwifery standars by using the 7-stages of varney midwifery care management and SOAP documentation procedure. Result The findings of this study indicated that despite the anemia problem faced by Mrs. “D” the delivery from the stage I to IV was considered to be running well and normal without any complications. Moreover, the newborn was also in good and healthy condition. This study concluded that the treatment of the patient was well conducted where the anamnesis and regular monitoring. Conclusion Furthermore, the assessment, analysis, and documentation related to all actions and treatment were documented. Hence, it could be suggested that the findings of this research were in line with previous theories.

Anemia and adverse outcomes in pregnancy: subgroup analysis of the CLIP cluster-randomized trial in India

BackgroundIron-deficiency anemia is a known risk factor for several adverse perinatal outcomes, but data on its impact on specific maternal morbidities is less robust. Further, information on associations between anemia in early pregnancy and subsequent outcomes are understudied.MethodsThe study population was derived from the Community Level Interventions for Pre-eclampsia (CLIP) trial in Karnataka State, India (NCT01911494). Included were women who were enrolled in either trial arm, delivered by trial end date, and had a baseline measure of hemoglobin (Hb). Anemia was classified by WHO standards into four groups: none (Hb ≥ 11 g/dL), mild (10.0 g/dL ≤ Hb < 11.0 g/dL), moderate (7.0 g/dL ≤ Hb < 10.0 g/dL) and severe (Hb < 7.0 g/dL). Targeted maximum likelihood estimation was used to estimate confounder-adjusted associations between anemia and a composite (and its components) of adverse maternal outcomes, including pregnancy hypertension. E-values were calculated to assess robustness to unmeasured confounding.ResultsOf 11,370 women included, 10,066 (88.5%) had anemia, that was mild (3690, 32.5%), moderate (6023, 53.0%), or severe (68, 0.6%). Almost all women (> 99%) reported taking iron supplements during pregnancy. Blood transfusions was more often administered to those with anemia that was mild (risk ratio [RR] 2.16, 95% confidence interval [CI] 1.31–3.56), moderate (RR 2.37, 95% CI 1.56–3.59), and severe (RR 5.70, 95% CI 3.00–10.85). No significant association was evident between anemia severity and haemorrhage (antepartum or postpartum) or sepsis, but there was a U-shaped association between anemia severity and pregnancy hypertension and pre-eclampsia specifically, with the lowest risk seen among those with mild or moderate anemia.ConclusionIn Karnataka State, India, current management strategies for mild-moderate anemia in early pregnancy are associated with similar rates of adverse maternal or perinatal outcomes, and a lower risk of pregnancy hypertension and preeclampsia, compared with no anemia in early pregnancy. Future research should focus on risk mitigation for women with severe anemia, and the potential effect of iron supplementation for women with normal Hb in early pregnancy.

Hemophilia Natural History Study (ATHN 7): Safety of Current Therapies for People with Hemophilia A or B

INTRODUCTION: The recent introduction of new therapies for people with hemophilia A and B (HA and HB) mandates careful monitoring of the safety of these treatments. The primary aim of ATHN 7: A Natural History Study of the Safety, Effectiveness, and Practice of Treatment for People with Hemophilia (NCT03619863) is to monitor the safety of current hemophilia therapies.METHODS: ATHN 7 is a longitudinal, prospective cohort study being conducted at 26 American Thrombosis and Hemostasis Network (ATHN)-affiliated sites. The study is approved by central and local institutional review boards. Any person with a diagnosis of congenital hemophilia A or B (factor VIII or IX activity < 50%) who receives care at a participating site is eligible for inclusion. Participants and/or a parent/guardian sign informed consent and assent prior to participation. Adverse events, including those events designated by the European Haemophilia Safety Surveillance group as well as other adverse events of special interest, are recorded and monitored. Demographic and clinical information are collected at baseline and at least quarterly through participant interview and medical record review. Descriptive statistics of medical history and demographic data as well as longitudinal data are used to characterize the study population.RESULTS: As of June 2021, a total of 391 participants had enrolled in ATHN 7. The median age of participants was 22.5 ± 17.8 years. Males represented 97.7% (382/391) of participants. Eighty-five percent (333/391) were not Hispanic. White participants comprised 82.6% (323/391) of the study population, while 7.9% (31/391) were Black/African American, 3.8% (15/391) were Asian, 1.8% (7/391) were of mixed race, and 3.8% (15/391) were of other or unknown race. The primary diagnosis of participants included 70.1% (274/391) with severe HA, 15.3% (60/391) with moderate HA, 7.2% (28/391) with mild HA, 4.1% (16/391) with severe HB, 2.0% (8/391) with moderate HB, and 1.0% (4/391) with mild HB. Nineteen percent (71/391) of participants had a documented history of an inhibitor at the time of enrollment with a mean peak inhibitor titer of 96.7 ± 214.3 Bethesda Units. Substitution therapy with a non-factor molecule was the primary medication for 43.4% (162/391) participants, while 4.3% (16/391) utilized a plasma-derived clotting factor concentrate, 28.4% (196/391) utilized a standard half-life, recombinant factor concentrate, 18.3% (126/391) utilized an extended half-life recombinant factor concentrate, 4.1% (28/391) utilized a bypassing agent, and 19.3% (133/391) utilized some other hemostatic agent. Continuous prophylaxis was the primary regimen for 79.1% (295/391) participants. The remaining 19.6% (73/391) of participants were on episodic therapy. Within the cohort of 391 participants, a total of 14 adverse events have been reported in 8 participants. No adverse events of special interest were reported. Redness or rash at injection site accounted for 64.2% (9/14) of the reported adverse events, all in participants receiving emicizumab. Two participants experienced bruising or bleeding while on emicizumab. Two participants on emicizumab were diagnosed with malignancy, neither found to be attributed to their therapy. One participant developed an allergic reaction to their standard half-life recombinant factor concentrate.DISCUSSION: Open to enrollment in January 2019, ATHN 7 has now collected 18 months of longitudinal safety data for therapies used to treat HA and HB in 391 participants, an addition of 12 months and 24 participants since our last report. As the study was designed to enhance representation of those utilizing substitution therapy, almost half of the participants were on emicizumab for prophylaxis of bleeding. Adverse events attributable to hemophilia therapy was limited to minor skin reactions. As previously reported, a single participant experienced delayed bleeding after closed head trauma (despite factor replacement and normal intracranial imaging at the time of the event), providing potentially important information on the risk of delayed bleeding from significant trauma in those receiving emicizumab. Over the coming year, participants in ATHN 7 will be transitioned to ATHN's new longitudinal natural history study, ATHN TRANSCENDS (NCT04398628). DisclosuresBuckner: Pfizer: Honoraria; Takeda: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Spark: Honoraria; Genetech: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Tremeau Pharmaceuticals: Consultancy, Honoraria; BioMarin: Consultancy, Honoraria; uniQure: Consultancy, Honoraria; American Thrombosis: Membership on an entity's Board of Directors or advisory committees; Hemostasis Network: Membership on an entity's Board of Directors or advisory committees. Carpenter: Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; Kedrion Pharmaceuticals: Honoraria; Genentech: Honoraria; Novo Nordisk: Honoraria. Raffini: Genentech: Consultancy; CSL Behring: Consultancy; HEMA Biologics: Consultancy; XaTek: Consultancy; Bayer: Consultancy. Zia: Takeda: Consultancy; Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees. Recht: Hema Biologics: Consultancy; Kedrion: Consultancy; Novo Nordisk: Consultancy; Octapharma: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; uniQure: Consultancy; Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy.

Quality of Life Is Impaired in Anemic MDS Patients, and May Still Remain Poor Even When Hemoglobin Improves

Background: Quality of life (QoL) is impaired in MDS.Aims: 1) To study QoL for various levels of anemia in MDS patients at diagnosis, 2) Compare with non-MDS controls. 3) Compare at MDS diagnosis to 1 year later.Methods: Patients in The Israel MDS registry fill out the EQ-5D QoL questionnaire. The evaluated parameters are: mobility, self-care, daily activities, pain/discomfort and anxiety/depression, each scored 0(normal), 1(mild/moderate), or 2(poor). They also evaluate their general health using a visual analogue scale (VAS), scoring from 0 (poor) to 100(excellent). Anemia was classified as none/normal (Hb≥12.5 g/dl), mild (10≤Hb<12.5), moderate (9≤Hb<10), severe (8≤Hb<9) or very severe (Hb<8). To assess QoL dynamics, MDS patients repeat this every 6 months .For controls, we used VAS to assess QoL of patients admitted to the Department of Medicine.Results: In total, 126 MDS patients participated: 19, 40, 17, 21 and 29, from normal to very severe anemia, respectively. Fig.1 shows mean QoL of the 5-parameters for all patients (A), and for each individual (B), as well as the mean VAS score for all patients (C) and for each individual (D). Anemic MDS patients show a wide QoL variability (patients with the same Hb behave differently, Fig.1, B, D). Also, note the drop in QoL from moderate to severe anemia (below 9 g/dl, p=0.06, for 5-parameter; p=0.01, for VAS).In the non-MDS controls (n=141), there was impaired QoL in anemic patients as compared to those without anemia (VAS, Figure 2; p=0.02). However, there was no significant difference in QoL among patients with various degrees of anemia.Follow-up QoL data (1 year) were available for 61 MDS patients (Figure 3). 27 (44%) increased Hb. 32 (52%) decreased, and 2 (3%), had no change. Of the 32 who decreased Hb, average QoL deteriorated by -11.88 [95%CI: -17.96, -5.79]; 24 patients (75%, Figure 3, left-lower quadrant) had decreased VAS score; some still had improved QoL (16%), or stayed the same (9%). Of the 27 who increased Hb, average VAS still reduced by -6.48 [-14.08, 1.12]. The minority increased QoL (26%), or stayed the same (19%). Most (56%) still deteriorated in QoL (right-lower). The QoL results using the 5 parameters was consistent.Conclusions: In this preliminary study: 1) Poor QoL in anemic MDS is variable and not linear, suggesting that other factors, in addition to Hb, affect QoL. 2) The sharp drop in QoL with Hb<9 g/dl (Figure 1, A and C from blue to pink), might lead to a therapeutic paradigm shift, with transfusion recommendations for patients with Hb<9. 3) QoL in anemic MDS patients might differ from non-MDS. 4) Anemia treatment and Hb rise are not necessarily associated with improved QoL. Larger studies will help determine QoL in MDS and other anemias and when and how to treat. [Display omitted] DisclosuresMittelman: Janssen · Roche · Novartis · Takeda · Medison / Amgen · Neopharm / Celgene / BMS · Abbvie · Gilead: Research Funding; Novartis · Takeda · Fibrogen · Celgene / BMS · Onconova · Geron: Other: Clini; Onconova · Novartis · Takeda · Silence: Membership on an entity's Board of Directors or advisory committees; MDS HUB: Consultancy; Celgene / BMS · Novartis: Speakers Bureau.