Hb Values Research Articles

Nursing Care For Patients Uterine Prolaps and Severe Anemia: Case Study

Uterine prolapse is a condition where the uterus herniates into the vagina as a result of ligament failure and fascial support. Uterine prolapse often occurs together with prolapse of the vaginal wall, which involves the bladder or rectum. menopausal women. If uterine prolapse is not treated immediately, it can cause other health problems such as bleeding which can cause severe anemia. The purpose of this study was to describe nursing care that can be carried out in patients with uterine prolapse with severe anemia. The method used is a descriptive method with a case study approach, while the instrument used is an observation format at the Bandung City Hospital and an assessment format from the Unpad Faculty of Nursing. The sample in this study was one patient with uterine prolapse with severe anemia. The nursing diagnoses found in patients are the risk of shock, acute pain, and risk of infection. The implementation provided is in the form of shock management which includes blood transfusion therapy, tranexamic acid therapy, and monitoring of vital signs. Management of uterine prolapse in the form of Kegel exercises and placing a pessary, pain management, as well as prevention of infection. As a result, it was found that there was an improvement in the Hb value from 7 gr/dL to 10 gr/dL, complaints of weakness and pain decreased, and the patient had been placed with a pessary type pessary ring with support. The existence of uterine prolapse is necessary to increase awareness to prevent the incidence of uterine prolapse and to minimize the impact that occurs due to uterine prolapse, as well as to increase patient awareness to conduct examinations to health services.

Impact Assessment of Iron and Folic Acid Supplementation with and Without Intensive Health Education in Pregnant Women of Rural Area of District Etawah: An Interventional Study

Background: Low birth weight , post-partum haemorrhage still births and maternal deaths are associated with anaemia in pregnancy. If prevalence of anemia will be reduced then there will be improvement in maternal and child health and its outcome. Aim & Objectives: To evaluate the changes in the hematological profile of the study subjects and to determine the impact of intensive health education intervention on anemia status of pregnant women. Methodology: A Community based interventional study was conducted among 200 Pregnant women of selected villages in rural area of Etawah district (100 women in each interventional and non-interventional group) using a self-developed, pre designed, pretested, structured and validated questionnaire. statistical package for social sciences (SPSS) software was used to analyse the data. Result: After health education intervention there is significant increase in the haematological profile of study participants of interventional group (p<0.05) as before intervention values of mean Hb was 10.58±1.79 gm/dl which became 11.72±1.48 gm/dl There were 34 (73.9%) participants in the interventional group that were originally anaemic before the study, but after the intervention, they became non-anaemic. Conclusion: Health education sessions helped the pregnant women to improve their knowledge regarding anemia in pregnancy, as well as improve their ability to select iron rich foods, increase compliance with iron supplementation, and raise their haemoglobin levels.

Haematological parameters of sheep in the semi-arid zone of North Eastern Nigeria

Haematological parameters of sheep in the semi-arid zone of North-Eastern Nigeria were studied between August 2022 and April, 2023. Blood was sampled from one hundred and sixty-eight sheep comprising of Yankasa, Balami and Uda (56 per breed) at the Federal University Gashua Teaching and Research Farm, Gashua abattoir and Garin Alkali goats and sheep markets. The study was carried out to determine the blood profile of prominent indigenous sheep breeds in the study area. Blood samples were carefully collected from the animals into labeled sterile bottles containing Ethylene diamine tetra-acetic acid for haematological examination. Data analyzed for the effect of breed, sex and age were not significantly affected (p>0.05) for packed cell volume (PCV) and haemaglobin (Hb) concentration. Consequently, values of PCV and Hb differed significantly (p<0.05) with season in favour of wet season, (40.87%) and (13.63g/dl) for PCV and Hb respectively. Values for red blood cell (10.18 x103/µL), mean corpuscular hemoglobin concentration (35.11g/dl), mean corpuscular hemoglobin (12.71 Pg), mean corpuscular volume (45.86 Fl) and white blood cell (10.72 x103/µL) were significantly higher (p<0.05) for Uda sheep. Adult sheep generally had significantly (p<0.05) higher values for haematologic parameters considered. It was concluded that there were breed, sex, age and seasonal differences in haematological parameters of the sheep breeds studied. The blood parameters needed to be monitored frequently and appropriately controlled to ensure stability and adequate health and nutritional status of sheep.

Feasibility and accuracy of noninvasive continuous hemoglobin monitoring using transesophageal photoplethysmography in porcine model

BackgroundContinuous and noninvasive hemoglobin (Hb) monitoring during surgery is essential for anesthesiologists to make transfusions decisions. The aim of this study was to investigate the feasibility and accuracy of noninvasive and continuous Hb monitoring using transesophageal descending aortic photoplethysmography (dPPG) in porcine model.MethodsNineteen landrace pigs, aged 3 to 5 months and weighing 30 to 50 kg, were enrolled in this study. A homemade oximetry sensor, including red (660 nm) and infrared (940 nm) lights, was placed in the esophagus for dPPG signal detection to pair with the corresponding reference Hb values (Hbi−STAT) measured by blood gas analysis. The decrease and increase changes in Hb concentration were achieved by hemodilution and transfusion. Metrics, including alternating current (AC), direct current (DC), and AC/DC for both red and infrared light were extracted from the dPPG signal. A receiver operating characteristic (ROC) curve was built to evaluate the performance of dPPG metrics in predicting the Hb “trigger threshold” of transfusion (Hb < 60 g/L and Hb > 100 g/L). Agreement and trending ability between Hb measured by dPPG (HbdPPG) and by blood gas analysis were analyzed by Bland-Altman method and polar plot graph. Error grid analysis was also performed to evaluate clinical significance of HbdPPG measurement.ResultsThe dPPG signal was successfully detected in all of the enrolled experimental pigs, without the occurrence of a continuous loss of dPPG signal for 2 min during the entire measurement. A total of 376 pairs of dPPG signal and Hbi−STAT were acquired. ACred/DCred and ACinf/DCinf had moderate correlations with Hbi−STAT, and the correlation coefficients were 0.790 and 0.782, respectively. The areas under the ROC curve for ACred/DCred and ACinf/DCinf in predicting Hbi−STAT < 60 g/L were 0.85 and 0.75, in predicting Hbi−STAT > 100 g/L were 0.90 and 0.83, respectively. Bland-Altman analysis and polar plot showed a small bias (1.69 g/L) but a wide limit of agreement (-26.02–29.40 g/L) and a poor trend ability between HbdPPG and Hbi−STAT. Clinical significance analysis showed that 82% of the data lay within the Zone A, 18% within the Zone B, and 0% within the Zone C.ConclusionIt is feasible to establish a noninvasive and continuous Hb monitoring by transesophageal dPPG signal. The ACred/DCred extracted from the dPPG signal could provide a sensitive prediction of the Hb threshold for transfusion. The Hb concentration measured by dPPG signal has a moderate correlation with that measured by blood gas analysis. This animal study may provide an experimental basis for the development of bedside HbdPPG monitoring in the future.

Abstract TMP10: Children With Sickle Cell Anemia Have Impaired Cerebrovascular Reactivity

Introduction: Sickle Cell Anemia (SCA) causes lower hemoglobin, leading to increased cerebral blood flow (CBF) to maintain cerebral oxygen metabolism (CMRO 2 ). Although CBF rises in childhood to meet higher CMRO 2 demands, further compensatory increases in CBF in children with SCA may tap into a limited hemodynamic reserve, increasing risk for infarct. Cerebrovascular reactivity (CVR) reflects hemodynamic reserve by measuring the vasculature’s response to vasoactive stimuli, particularly in the gray matter (GM). We hypothesized that children with SCA have lower GM CVR, regardless of CMRO 2 . Methods: We used magnetic resonance imaging of children with and without SCA to collect pseudocontinuous arterial spin labeling (pCASL) for CBF, asymmetric spin echo for oxygen extraction fraction (OEF) and blood oxygen level dependent (BOLD) data correlated with hypercapnic challenges for CVR. Lab draws confirmed Hemoglobin (Hb) values. CMRO 2 was calculated as CBF x OEF x Arterial Oxygen Content (1.36 x Hb x SpO 2 ). Continuous variable differences between groups were analyzed using the Mann-Whitney U test, and categorical variables using the Fisher’s exact test. Linear regression assessed the relationship between CVR and Hb. Reported significant relationships survived multiple comparisons correction. Results: A total of 35 participants, ages 8–22 years had quality CVR data [9 SCA subjects (5 male) and 26 controls (9 male)]. Of these, 8 SCA and 20 controls had adequate quality metabolic data. The groups are matched by age (p=0.56) and sex (p=0.43). Children with SCA had higher GM CBF (62.0 v 49.3 mL/100g/min; p=0.03), but similar GM CMRO 2 (1.81 v 1.42 mL/100g/min; p=0.07) than controls. GM CVR was significantly lower in SCA than controls (0.17 v 0.27 %/mmHg; p=0.0003). Lower CVR was associated with lower Hb (Figure) after adjusting for age and sex (p &lt;0.0001). Conclusion: Lower GM CVR in children with SCA indicates a lower hemodynamic reserve, likely related to the degree of anemia.

Pemberdayaan Ibu Kader PKK dalam Upaya Pencegahan Stunting di Desa Sari Gadung Kabupaten Tanah Bumbu Kalimantan Selatan

In South Kalimantan, the stunting incidence rate in 2022 will be 24.6%, more significant than the national prevalence rate of 21.6%. Tanah Bumbu is one of the districts located in South Kalimantan Province, with the incidence of stunting in Tanah Bumbu district, according to SSGI data, reaching 16.1%. Sari Gadung Village is one of the villages in Simpang Empat District, Tanah Spice Regency. This village has a potentially productive group, namely Posyandu Cadres. Data on the incidence of stunting in Tanah Spice Regency reached 16.1%. Providing health supplements to the community is needed to improve community health in Sari Gadung village and prevent stunting. This community service activity aims to prevent stunting by providing health checks, including checking Hb, glucose, uric acid, and blood pressure, and providing blood supplements. The method is that adult female patients are given drug information regarding the use of iron and folic acid drugs, and then their Hb, glucose, uric acid, and blood pressure are checked. The results of this activity showed that the number of patients who took part in the activity was 37, the average Hb value was 15.9 g/dL, the average uric acid was 8.6 mg/dL, the mean glucose was 112.5 mg/dL, and the blood pressure was 122/82 mmHg. The conclusion is that the results of the health examination at the posyandu in Sari Gadung village are still in the normal category.

Association between Serum Iron, Serum Ferritin Levels, and Severe Early Childhood Caries: A Case-Control Study.

The presence of extensive dental caries leads to pain, inflammation, and discomfort and hence interferes with their nutritional intake, which includes iron deficiency anemia. This study was undertaken to determine whether any correlation exists between severe early childhood caries (S-ECC), serum iron, and serum ferritin levels in children. A total of 688 children were examined in the age-group of 2-6 years, and 82 children who fulfilled the selection criteria were equally divided into group I, that is, case group (carious group n = 41) and group II, that is, control group (caries-free group n = 41), on the basis of decayed, missing, and filled primary teeth (dmft) scores. All the selected children in both groups underwent blood investigations through phlebotomy for assessment of serum iron and serum ferritin levels. The mean values of variables, that is, hemoglobin (Hb), serum iron, serum ferritin, total iron-binding capacity (TIBC), and unsaturated iron-binding capacity (UIBC), are lower in the case group when compared to control group. The differences observed were statistically significant in case of dmft and UIBC values at p < 0.05 but not significant in cases of other variables like Hb, serum iron, serum ferritin, and TIBC values. An inverse relationship was found between S-ECC, serum iron, and serum ferritin levels, but the evidence is still inconclusive. Atri Y, Garg N, Pathivada L, et al. Association between Serum Iron, Serum Ferritin Levels, and Severe Early Childhood Caries: A Case-Control Study. Int J Clin Pediatr Dent 2023;16(S-3):S288-S292.

Antioxidant associated chemoprophylaxis effect of natural spice and green vegetable on hepatotoxicity.

This is a case control and cohort study, conducted at Department of Biochemistry in FUAST, compressing 24 number of albino Wistar rats. Illicium verum (star anise) natural spice and green vegetable broccoli are used for chemo-preventive herbal treatment in relation with vitamin C antioxidant activity. Hepatotoxicity was induced in liver of model rats by giving interperitoneally single injection of 200 mg/kg bod weight (B.W) of N-nitrosodiethylamine and orally giving 1 mg/kg BW phenobarbital for 14 days during disease prorogation period. The vitamin C analysis from Illicium verum (star anise), green broccoli, orange juice, orange peel and orange pulp was done by iodometric quantitative and qualitative titration method. Rats were given compound according to their bodyweight as 1 mg/kg B.W. After 14 days (Disease Promotion and Propagation Period) and 28 days (Disease cure period) of treatment behavioral activity was monitored by locomotors activity in open field experiment, stimulatory activity in home cage and anxiolytic effects observed in light and dark apparatus and also in T maze. Behavioral activity were significantly increased in Illicium verum and green broccoli treated rats. Hematological study including hemoglobin (Hb), white blood cells (WBC), red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW) and Platelets was done by abbot laboratory analyzer cell. The value of Hb and RBC was also significantly increased in star anise and broccoli treated rats, showed proper function of RBC in microcirculation. WBC was also in normal range revealed that no disease regards to bone marrow and leukemia's. The biochemical activity of rats including urea, creatinine, total protein, albumin, globulin, A/G ratio, amylase and calcium in blood serum were analyzed while, liver health or performance was also determined by LFT (liver function test). Behavioral and laboratorial variables were analyzed by using SPSS v. 20 and p-value < 0.05 was considered statistically significant. The study report noticeable significant effect of Illicium verum and broccoli on hepatotoxicity of experimental model. Recent experimental study statistical outcomes show reciprocal relationship between the consumption of vegetable diet and natural spice with the risk of Hepatotoxicity. Thus, the aim of the study is to enhance the function of star anise or illicium verum natural spice and green vegetable broccoli as an anticancer or chemoprophylaxis agent.

Comparison of the Changes in Blood Carboxyhemoglobin and Bilirubin Levels and Their Effects on Neonatal Hyperbilirubinemia in Neonates Born by Cesarean Section versus Vaginal Delivery

Aim: The study aimed to investigate whether there are differences in carboxyhemoglobin, bilirubin and hemoglobin values of neonates born by normal spontaneous vaginal birth (NSVD) (without anesthesia) and elective spinal cesarean section (CS) and its effect on neonatal jaundice. Materials and Methods: A total of 110 healthy neonates without any risk factors for neonatal hyperbilirubinemia were included in the study. There were fifty-five neonates in both NVSD and spinal CS groups. COHb, bilirubin and Hb values which were measured from umbilical cord blood (as cord) and capillary blood taken from the heel 4-6 hours after birth (as post cord) were recorded. Results: No statistically significant difference was found between the groups in terms of birthweight, maternal age, APGAR scores, and gender (p&gt;0.05). There was a statistical difference between the groups according to the mean of gestational age, and it was observed that the mean of gestational age in spinal CS group was lower than in NSVD group (38.30±1.2 and 39.16±1.39 respectively) (p=0.001). Umbilical cord COHb levels in spinal CS group were higher than in NSVD group, but there was no statistically significant difference between groups (1.01±0.15 and 0.99±0.20 respectively, p=0.22). Furthermore, the differences between groups in term of mean of bilirubin and Hb levels in cord and post cord were not statistically significant (&gt;0.05). But, it was determined that post cord COHb levels were higher than in NVSD group, and this difference was statistically significant (p=0.028). Additionally, it was found that the mean rank of COHb, bilirubin, and Hb in cord and post cord values were statistically significantly different between the groups (p &lt; 0.05). Conclusion: It should be kept in mind of that the anesthetic agent may also be a factor in bilirubin increases that occurs in neonatal hyperbilirubinemia without an underlying risk factor.

Hematology in ornamental discus fish Symphysodon discus from Amazonian, Brazil.

Symphysodon discus is known in the world of aquariums for its market value, beauty, and behavior. However, more substantial information about its physiology and biology must be available, which can hinder its development and maintenance in breeding systems. The study evaluated the blood biochemistry and erythrogram of 20 specimens of S. discus captured in the municipality of Barcelos, Amazonas, with an average weight of 89.80 ± 7.13 g and an average length of 13.48 ± 0.55 cm. The erythrogram evaluated variables such as hematocrit (Ht), hemoglobin (Hb), red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). Blood biochemistry was analyzed, including cholesterol levels, total proteins, triglycerides, glucose, urea, and chlorides. Intra-specific variations were observed between the surveyed individuals about the Hb, MCV, and MCH values. The values of triglycerides, cholesterol, and chlorides were elevated compared to other cichlids. This study may be useful to serve as a parameter to indicate the normal health conditions of this Amazonian cichlid. It can be applied in studies for ornamental fish farming and actions for managing and conserving the species.

Evaluation of Iron Status in Children Presenting with Febrile Seizure in a Tertiary Health-care Facility

Abstract Introduction: The aim of this study was to investigate the relationship between iron deficiency anemia (IDA) and febrile seizures (FS) in children. Materials and Methods: The study included 100 cases of FS in children between the ages of 6 and 60 months, including both simple and complex FS. Children in the same age range who had a fever but no seizures made up the control group. The various hematological parameters reflecting the iron status, including hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), red-cell distribution width (RDW), serum ferritin, and total iron-binding capacity (TIBC), were evaluated in both groups to ascertain the relationship between the iron status and the FS. Results: Male-female ratio in children with and without FS were 1.2:1 and 1.3:1, with a mean age of 25.16 ± 11.75 and 24.37 ± 11.75 months, respectively. Age and gender distribution were comparable between the two groups (P = 0.719 and P = 0.851, respectively). The mean values for Hb, MCV, MCHC, RDW, ferritin, and TIBC among children who had FS were 11.030.98 g/dL, 66.1810.97 fl, 32.421.38 pg/L, 14.881.13, 46.5432.64 ng/mL, and 419.7672.49 g/dL, respectively. In contrast, the readings for the control group’s children were 11.91 0.78, 67.94 11.06 fl, 32.80 0.60 pg/L, 14.16 1.01, 59.20 27.52 ng/mL, and 378.65 60.87 g/dL, respectively. Except for the mean MCV, each of these variances was statistically significant. Conclusions: Our results suggest that IDA is a major risk factor for FS since it was more common in the case group than in the control group.

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

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

Pengaruh Pemberian Buah Kurma pada Ibu Hamil Trimester III dengan Anemia terhadap Kadar Hemoglobin

Anemia is an important health problem throughout the world. Approximately 51% of pregnant women suffer from anemia twice as often as non-pregnant women. Anemia in pregnancy is those who have Hb levels &lt;11 gr% in the first trimester and third trimester and Hb levels &lt;10.50 gr%. Dates are a food that contains high energy with an ideal composition, containing carbohydrates, tryptophan, omega-3, vitamin C, vitamin B6, Ca2+,Zn, and Mg. Research design with Quasi Experimental non-Equivalent control group design. The research sample size was 15 pregnant women.The research results showed that the hemoglobin level before giving dates was the lowest 9 gr/dL and the highest 15 gr/dL. And the average is 10 gr/dL. Hemoglobin level values after giving dates were the lowest, 11.5 gr/dL, the lowest and the highest, 16 gr/dL. And the average is 13 gr/dL. The Shapiro-Wilk value is 0.039 &lt; 0.05, so the data is not normal. Because the data was not normal, the test was continued with the non-parametric Wilcoxon test. Positive ranks 15 means that all 15 samples experienced an increase in HB from the previous value to the next value. Meanwhile, mean rank 8 is the average increase in HB. The positive number is 120,Ties 0 means there is no similarity in HB values before and after. This research concludes that there is an effect of giving dates on increasing hemoglobin levels in pregnant women.

The Effect of Inflammatory Markers in the Hemogram Parameters of Pregnant Women with Thyroid Disease on Obstetric and Neonatal Outcomes

Aim: This study aimed to determine the differences in hemogram parameters, especially in inflammatory markers and perinatal and neonatal outcomes of pregnant women with thyroid disease, and to examine the effects of these differences on pregnancy outcomes. Material and Methods: The data of 80 pregnant women diagnosed with thyroid disease according to the American Thyroid Association (ATA) criteria at the first admission between 2016 and 2019 and 100 pregnant women whose thyroid hormone levels were within the normal reference range were retrospectively analyzed. Obstetric outcomes such as type and time of delivery, and the presence of additional disease during pregnancy, and neonatal outcomes such as weight, gender, and Apgar score at birth were compared. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), white blood cell (WBC) count, and hemoglobin (Hb) and mean platelet volume (MPV) values, which are accepted as inflammation markers, were also compared between groups. Results: There was no significant difference between hypothyroid and hyperthyroid pregnant women in terms of Hb (p=0.319) and PLR (p=0.341) values. Third-trimester WBC (p=0.015) values were higher and MPV (p=0.007) values were lower in the hypothyroid pregnant women compared to the control group. The highest NLR (p=0.005) value was observed in the hypothyroid group. Comorbidities were found to be 27.4% (n=20) in the hypothyroid group, 14.3% (n=1) in the hyperthyroid group, and 1.0% (n=1) in the control group (p&amp;lt;0.001). Conclusion: Pregnant women with thyroid disease may have differences in hemogram parameters, especially in inflammatory markers, and these differences may affect pregnancy outcomes.

Developing Topics.

Semantic verbal fluency (SMF) has been identified as an early marker of mild cognitive impairment (MCI). Anemia and some micronutrient deficiencies (MD) have been considered as risk factor for MCI. In Mexico, it has been poorly studied the nutritional drivers associated to MCI. Anemia and MD are frequent in vulnerable Mexican population but controversial exist around the criteria to define such entities in older adults (OA).The aim is to analyse the association between hemoglobin concentration, iron and B12 status, as well as the causes of anemia with SVF in older Mexican adults. 802 OA from 4 urban localities in Campeche and Yucatan -most of them considered themselves as Mayan indigenous- donated a capillary and venous blood sample. Hb (g/dL) was measured in capillary blood using Hemocue. Ferritin, vitamin B12, transferrin receptors (stfr), and other biomarkers were analysed in serum. The causes of anemia were classified as: Iron deficiency (ID), B12 deficiency (B12D), inflammatory, renal, multiple and unexplained. We explored the quartiles (Q) of Hb -sex adjusted-, s-ferritin, and stfr with SVF. Anemia, causes of anemia and MD were modelled separately using multiple linear regression models adjusted by confounders. Anemia, ID and B12D affected to 35.3%, 5% and 10% of OA, respectively. The mean of SVF was 13-5±6.5 words. The Q1 [coef = -1.4, p = 0.025], Q2 [coef = -1.46, p = 0.016] and Q3 [coef = -1.13, p = 0.05] of Hb were negatively associated with SVF in comparison with Q4. No association was observed between the quartiles of s-ferritin, stfr, ID or B12D with SVF. Total anemia (-0.9, p = 0.047), and particularly B12D anemia (-3.5, p = 0.018), were associated to lower SVF vs non-anemics. Higher Hb values (≥13.3 g/dL for women and ≥14.7 g/dL for men) above the cut-off of anemia were positively associated with SVF independent of MD. This finding suggests that normal Hb values in those ranges of Hb might hide a declining in brain function secondary to an inadequate delivery of cerebral oxygen. Those with B12D anemia had the worse SVF performance. It is necessary to identify the main drivers for the optimal Hb range where the OA is functional independent to target early interventions.

Recombinant erythropoietin in autoimmune hemolytic anemia with inadequate bone marrow response: a prospective analysis

AbstractUp to 30% of patients with autoimmune hemolytic anemia (AIHA) show inadequate bone marrow (BM) compensatory response with inappropriately low levels of reticulocytes and endogenous erythropoietin. Ineffective BM compensation is associated with more severe anemia, transfusion need, and hospital admission, and treatment with recombinant erythropoietin (rEPO) may be beneficial. Here, we prospectively analyzed the efficacy and safety of rEPO in a single-center cohort of 47 patients with AIHA with inadequate reticulocytosis and endogenous erythropoietin at baseline. Epoetin alpha 40 000 international units per week were administered subcutaneously until hemoglobin (Hb) >11 g/dL and then tapered off. Overall response was 55% at 15 days, 74% at 1 month, 74% at 3 months, 80% at 6 months, and 91% at 12 months. Consistently, Hb values significantly increased from baseline to each subsequent time point (P<.001) with a median increase of +1.4, +2.4, +3.4, +3.8, and +4.4 g/dL, respectively. Transfusion needs reduced from 30% to <10% at 15 days and thereafter (P < .001). Concomitant medications included prednisone or methylprednisolone (N = 40, stable since >2 weeks from enrollment), mycophenolate mofetil (N = 1, ongoing since >3 months from enrollment), and rituximab (N = 7 patients with cold agglutinin disease from day 8). No association between concomitant medications and response to rEPO was found. Treatment was generally safe without rEPO-related severe adverse events. The comparison with an AIHA population not treated with rEPO showed a significant benefit of rEPO at 15 days and 1 month on response and Hb increase. These data support the use of rEPO as an add on to standard immunosuppression in AIHA with inadequate BM compensation. This trial was registered at www.clinicaltrials.gov as #NCT05931718.

Association of Hemoglobin Levels with Healthcare Resource Utilization and Costs in Non-Transfusion-Dependent α- and β-Thalassemia: A Retrospective Observational Study Using Real-World Data

Introduction: Alpha (α)- and beta (β)-thalassemia result from reduced synthesis of α- or β-globin, respectively, leading to ineffective erythropoiesis, chronic hemolytic anemia (HA), and related complications. Thalassemia can also be characterized phenotypically as transfusion-dependent thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT). Decrease in hemoglobin (Hb) has been linked to increased risk of comorbidities and number of comorbidities in NTD β-thalassemia. Healthcare resource utilization (HCRU) has been analyzed in TDT in the US, but there is limited research on the association of Hb levels with HCRU and costs in α- and β-NTDT. Objective: To assess the association of average Hb levels with HCRU and costs in adult patients with α- and β-NTDT using retrospective claims data. Methods: This study analyzed data from the Merative ® MarketScan ® Commercial, Medicare, and Lab Results Databases for patients with thalassemia and no evidence of other HAs who were ≥18 years of age on the index date (date of the first observed diagnosis code for α- or β-thalassemia). Patients were stratified by type of thalassemia (α- or β-thalassemia) and by transfusion dependence (NTDT or TDT). NTDT was defined as &amp;lt;8 transfusions within 12 months of follow-up or with &amp;gt;42 days between any 2 adjacent transfusions. To evaluate if the results in NTDT were driven by patients with β-NTDT, patients with α-NTDT were also analyzed separately. Hb levels, HCRU (inpatient [IP] admissions, outpatient [OP] visits, and emergency room [ER] visits), and costs were assessed during a variable-length follow-up period (at least 12 months from the index date to end of plan enrollment, end of study, or IP death, whichever occurred first). Available Hb levels were averaged across the follow-up period for each patient. HCRU (number and type of service) and costs (US dollars) were converted to per-patient per-year values. All dollar estimates were inflated to 2020 (using Medical Care Component of Consumer Price Index). To assess the association of Hb levels with HCRU and cost outcomes, univariate regression analyses with negative binomial models were conducted. Percent changes in cost and incidence rate ratios of HCRU associated with 1 g/dL decrease in Hb level and corresponding 95% confidence intervals and p values (with significance level set to 0.05) were reported. Results: In the Commercial/Medicare database, 4077 adult patients with thalassemia and a variable length follow-up of at least 12 months were identified (median length of follow-up: 943 days). Of these, 909/4077 (22.3%) had at least 1 Hb value during the follow-up period in the Lab Results database, including 400 patients (44.0%) with α-thalassemia, 509 (56.6%) with β-thalassemia, 898 (98.8%) with NTDT (α or β), and 11 (1.2%) with TDT (α or β). The average Hb value per patient with NTDT (α and β; N=898) was 11.3 g/dL (11.5 g/dL for α-NTDT; N=400). In the NTDT group, 4.1% had at least 1 transfusion in first 12 months of follow up (3.6% had 1-3 transfusions and 0.5% had 4-7). For all patients with NTDT, with each 1 g/dL decrease in Hb, the number of IP admissions increased by 17%, OP visits by 8%, and ER visits by 11% (all p&amp;lt;0.001). For patients with α-NTDT, with each 1 g/dL decrease in Hb, the number of IP admissions increased by 15%, OP visits by 6%, and ER visits by 16% (all p&amp;lt;0.01; Table 1). Regarding costs for all patients with NTDT, with each 1 g/dL decrease in Hb, total healthcare costs increased by 15% (p&amp;lt;0.001), IP costs by 56% (p&amp;lt;0.001), OP costs by 12% (p&amp;lt;0.001), ER costs by 20% (p&amp;lt;0.003), and prescription costs by 12% (p=0.061). For patients with α-NTDT, with each 1 g/dL decrease in Hb, total healthcare costs increased by 14% (p&amp;lt;0.001), IP costs by 47% (p&amp;lt;0.001), OP costs by 10% (p&amp;lt;0.001), ER costs by 30% (p&amp;lt;0.003), and prescription costs by 9% (p=0.322). It is possible that because of incorrect/incomplete coding, some patients with thalassemia minor may have been included in the analyses, which may account for the higher-than-expected Hb levels in the NTDT cohorts. This may, in turn, underestimate the impact of Hb level on HCRU and costs. Conclusion: In this study, each 1 g/dL decrease in Hb was associated with significantly higher HCRU and costs. This association was seen in both the NTDT group and α-NTDT subgroup suggesting that both α-NTDT and β-NTDT experience this burden. This analysis indicates that raising Hb levels in patients with both α- and β-NTDT could result in reduced HCRU and costs.

Phase II Study Assessing Safety and Preliminary Efficacy of High Dose Intravenous Ascorbic Acid in Patients with TET2 Mutant Clonal Cytopenias

Background: Clonal cytopenia(s) of undetermined significance ( CCUS) is defined as persistent cytopenias arising in the context of myeloid neoplasm ( MN)-associated somatic mutations ( MT) in hematopoietic stem cells. Patients ( PTs) with TET2MT CCUS have a high probability of progression to MN. To date, no FDA-approved therapies exist for CCUS, and PTs often have similar cytopenias/transfusion needs as those with myelodysplastic syndromes ( MDS). TET2 is an ascorbic acid (AA)-dependent dioxygenase that catalyzes the conversion of 5-methylcytosine ( 5mC) to 5-hydroxymethylcytosine ( 5hmC), providing rationale to study high-dose IV (HI)-AA in TET2MT CCUS. Here we report the final results of this pilot trial. Methods: This is an investigator-initiated, single-institutional, phase II trial assessing the safety and efficacy of HI-AA in PTs with TET2MT CCUS (NCT03418038). PTs≥ 18 years with ≥1 TET2MT with or without additional somatic MTs, without prior treatment, and with any of the following laboratory criteria: (1) hemoglobin ( Hb) ≤10g/dL, (2) absolute neutrophil count ( ANC) ≤1(10^9/L), (3) platelet count ( PLT)≤100 (10^9/L) were eligible. HI-AA (1g/kg, maximum 100g) was given 3 times weekly for 12 weeks. The primary endpoint was hematologic response rates determined by MDS IWG 2018 criteria at week 20. (Platzbecker Blood 2018) and reported as hematologic improvement ( HI)- erythropoietic ( HI-E), platelets ( HI-P), neutrophils ( HI-N). Secondary endpoints include safety and adverse events ( AEs), graded by NCI-CTCAE v4.03. Correlative studies include changes in TET2MT variant allele fraction ( VAF), in vitro colony formation and differentiation, global and sequence-specific DNA methylation/hydroxymethylation, and quantitative 5hmC estimated by IHC in bone marrow biopsy specimens. Results: Ten patients were enrolled, with a median age of 71.4 (range: 65, 79) years, 8 (80%) males. The median number of mutations was 3, with 9 (90%) having co-mutations. All PTs but one [-Y] had normal karyotype. Baseline Hb levels were normal in all but one who was red blood transfusion dependent. Five (50%) PTs were thrombocytopenic, and 5 (50%) PTs had ANC&amp;lt;1 (10^9/L). ( Table). HI-AA was well tolerated with the most common AEs being infusion-related polyuria (40%) and polydipsia (40%, 3 Grade 1, 1 Grade 2). One (10%) PT had constipation and headaches (both Grade 1), and 1 (10%) experienced dyspepsia. No treatment-related Grade 3 or 4 AEs' or deaths were reported. The median follow-up duration was 16.8 months (range: 9.4, 24.1). Overall, no PTs met the criteria for HI. There were no significant differences with regards to median Hb, PLT, and ANC values at baseline, week 20, and 1-year (median Hb: 13.3, 12.5, and 12.7 g/dL, p=0.93; PLT: 97 vs. 120 vs. 92.5X10^9/L, p&amp;gt;0.99, and ANC: 0.9 vs. 1.2 vs. 1.3X10^9/L, p=0.99). By CTCAE grading criteria for cytopenias, 3 (30%) PTs had an improvement in severity of cytopenias, while 2 had worsening. One (10%) PT had an improvement in PLT (baseline vs. week 20: 62 vs 192X10^9/L) but was morphologically deemed to meet criteria for CMML-1 at week 20. Four (40%) PTs met criteria for disease progression (PT_4, 7,8,10); CMML-1- 2 and MDS-2. The median time to progression was 5 months (95% CI: 4.9, unreached). Two PTs had mutational clonal evolution, with 1 (PT_8) acquiring a RUNX1 (VAF: 20%) and 1 (PT_9) acquiring 2 CBL mutations (both VAF:4%) at one-year follow-up. There were no significant differences regarding the clinical characteristics or the TET2 variants between PTs who had stable disease vs. progression. There were no significant differences in TET2 VAF at baseline, week 20, and 1-year (median: 39% vs. 43% vs. 42%, p=0.54). We profiled changes in 5-mC and 5-hmC (Ilumina EpicArray) in PTs pre- and post-IV AA treatment and did not observe global changes. However, we were able to highlight site-specific changes in differentially methylated regions, largely resulting in hypomethylation at enhancer sites and affecting actively transcribed states in PTs with an improvement in cytopenia(s) severity by CTACE criteria ( Figure). Conclusion: We report the final safety and efficacy analysis of HI-AA in PTs with TET2 MT CCUS. The trial data suggest that HI-AA is safe and well tolerated. Although there were no significant responses by IWG MDS criteria, alleviation in severity of cytopenias in a subset of PTs (n=3) along with correlative epigenetic changes in enhancer regions, needs further exploration.

Efficacy and Safety Is Maintained in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan for up to 3 Years

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening disease characterized by complement-mediated hemolysis and thrombosis. Pegcetacoplan, the first complement component 3 (C3) inhibitor for PNH, increased hemoglobin (Hb) levels in complement component 5 inhibitor (C5i)-experienced and -naive adult patients with PNH in 2 phase 3 clinical trials (PEGASUS [NCT03500549] and PRINCE [NCT04085601], respectively). This integrated analysis of data from the pivotal phase 3 trials and the subsequent open-label extension (study 307; NCT03531255) evaluated the long-term efficacy and safety of pegcetacoplan for PNH treatment. Methods: For this integrated analysis, baseline was defined as the initiation of pegcetacoplan, regardless of when in the trials this occurred. Patients initially received pegcetacoplan 1080 mg subcutaneously twice weekly; dose escalations to once every 3 days or 3 times weekly were permitted. Efficacy was evaluated from baseline up to Weeks 132 (2.5 years, PRINCE) and 156 (3 years, PEGASUS) by Hb, lactate dehydrogenase (LDH; upper limit of normal [ULN] 226 IU/L), absolute reticulocyte count (ARC), and indirect bilirubin values; Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores; and transfusion avoidance rates (percentages of patients who did not require a transfusion during treatment). Safety was assessed by incidence of adverse events (AEs) and serious AEs (SAEs) during pegcetacoplan monotherapy for up to 3 years. Results: Of the 133 patients in the phase 3 trials (PEGASUS, 80; PRINCE, 53), 114 enrolled in the extension study (PEGASUS, 64; PRINCE, 50). At least 75% had received a transfusion in the year before enrolling in PEGASUS or PRINCE. Prior to pegcetacoplan initiation, mean (SD) Hb levels were 8.95 (1.09) g/dL in PEGASUS, 9.27 (1.44) g/dL in PRINCE, and 9.08 (1.24) g/dL in the total population; median (interquartile range) LDH levels were 217.0 (184.8, 276.5) IU/L in PEGASUS, 1964.0 (1409.0, 2503.3) IU/L in PRINCE; and mean (SD) FACIT-Fatigue scores were 31.6 (11.7) in PEGASUS, 36.6 (10.0) in PRINCE, and 33.6 (11.3) in the total population. After pegcetacoplan initiation, mean Hb levels markedly improved from baseline and remained stable through Weeks 132 (2.5 years, PRINCE) and 156 (3 years, PEGASUS) ( Figure). Median LDH rapidly decreased and stabilized below the ULN ( Figure). Improvements in ARC and indirect bilirubin were similarly maintained. Average FACIT-Fatigue scores increased (indicating less fatigue) rapidly and were maintained near the general population norm of 43.6. Annual transfusion avoidance ranged from 71%-79% in PEGASUS and 80%-86% in PRINCE, with 52% of patients from PEGASUS avoiding transfusion for up to 3 years of pegcetacoplan treatment and 67% of patients from PRINCE avoiding transfusion for up to 2.5 years. Overall, &amp;gt;92% patients had compliance rates of at least 95%. Over 3 years, most patients experienced an AE; SAEs were reported in 50.0% of patients, with 4.5% experiencing a SAE deemed related to pegcetacoplan. Overall, 17 patients discontinued pegcetacoplan due to an AE; of those, 9 discontinued due to a hemolytic disorder, 7 of which discontinued within 1 year of starting pegcetacoplan. Over 3 years, 4 (3.0%) deaths occurred, none were deemed related to pegcetacoplan; 3 (2.3%) patients experienced a thrombotic event (in the context of multiple associated comorbidities or discontinuation of pegcetacoplan) and no cases of meningitis were reported. Overall, no new or unexpected safety findings were identified. Conclusions: Rapid improvements in Hb, LDH, ARC, indirect bilirubin, and FACIT-Fatigue values were observed and maintained up to 3 years in C5i-experienced patients and up to 2.5 years in C5i-naive patients. The transfusion burden was significantly reduced. No new safety findings were identified. This analysis demonstrates sustained efficacy and continued safety of long-term pegcetacoplan for patients with PNH, regardless of prior C5i treatment.

Predicting Hemoglobin Response to Hydroxyurea and Voxelotor in Adults with Sickle Cell Disease

Background: Chronic anemia contributes to morbidity and mortality in sickle cell disease (SCD) and is associated with stroke, leg ulcers, pulmonary hypertension (PH), priapism, and chronic kidney disease (CKD). Treatment options for anemia in SCD are limited - hydroxyurea (HU) is the gold standard treatment, but hemoglobin (Hb) responses to HU in adult and pediatric cohorts appear to be modest at best. We evaluated the Hb response to HU and voxelotor in an adult SCD cohort, as well as baseline factors associated with Hb response to HU. Methods: This longitudinal study was based on retrospective chart review of patients with SCD followed in the UPMC Adult Sickle Cell Program, with drug start dates between 2007 and May 2023. Subjects with a documented start date for HU/voxelotor, a baseline Hb ≤ 3 months prior to starting drug, and a follow-up Hb at 1 or 3 months (± 2 weeks) after the start date were included. Those who self-discontinued therapy were excluded. Baseline factors were collected within ≤ 3 months of drug start date. Given the small number of subjects on voxelotor, factors associated with Hb response were evaluated in the HU group only. Baseline factors were reported using descriptive statistics and compared between Hb responders (defined as Hb increase ≥ 1 g/dL from baseline - a common outcome measure in clinical trials of anti-polymerization agents) and non-responders. Linear regression analysis was performed with change in Hb at 1 month (ΔHb) as the outcome of interest, as Hb levels at 1 and 3 months were highly correlated (r=0.905, p&amp;lt;0.001) and there were fewer missing values for Hb at 1 month. Variables associated with ΔHb with p&amp;lt;0.25 were included in a multivariable regression model. P&amp;lt;0.05 was considered significant, and 95% confidence intervals (CI) were reported. Results: Out of 394 subjects, 93 met eligibility criteria, including 88 starting HU and 5 starting voxelotor. One subject in the voxelotor group was on stable-dose HU. Median ages at start of HU and voxelotor were 24.5 years (range 13-57) and 45.4 years (range 22-60), respectively. Females accounted for 50/88 (56.8%) HU subjects and 4/5 (80%) voxelotor subjects. HbSS genotype made up 47/88 (53.4%) of the HU group and 4/5 (80%) of the voxelotor group. Median baseline Hb in the HU group was 9.8 g/dL, with a median increase of 0.2 g/dL and 0.3 g/dL at 1 and 3 months, respectively. In contrast, baseline Hb in the voxelotor group was 7.2 g/dL with a median increase of 1.9 g/dL and 2.1 g/dL at 1 and 3 months, respectively. Hb response was observed in 21/88 (24%) subjects in the HU group vs. 4/5 (80%) subjects in the voxelotor group. Among responders, median Hb increase was 2.2 g/dL (1 month) and 2.0 g/dL (3 months) with HU. Median baseline ferritin was 200 ng/mL in the HU group and 2413 ng/mL in the voxelotor group. In the HU group, lower baseline Hb was associated with female sex, severe SCD genotype (HbSS, HbSβ 0), and higher HbS%, WBC count, platelet count, and hemolytic markers (lactate dehydrogenase, total bilirubin, and reticulocyte count) (data not shown). Demographic/clinical variables were not associated with Hb response, except for male gender at 3 months (Table 1). Lower baseline Hb, RBC count, and hematocrit and higher MCHC, HbS%, LDH, and total bilirubin were associated with positive Hb response at 3 months. HbF% was higher in the responder groups but was not significant. In a multivariable linear regression model including age, PH, leg ulcers, CKD, baseline Hb, platelets, and total bilirubin as explanatory variables, baseline Hb was negatively associated with ΔHb (B = -0.26, CI = -0.40 to -0.12, p&amp;lt;0.001). History of leg ulcers was also negatively associated with ΔHb but was not significant (B = -0.94, CI = -2.01 to 0.13, p=0.083). Conclusion: Overall, Hb response to HU was much lower compared to voxelotor, though in the 24% of subjects who responded to HU, the Hb increase was comparable. Though limited by small sample size, our data revealed that patients started on voxelotor vs. HU were older, more anemic, and more iron overloaded. Subjects with lower baseline Hb had a more robust Hb response to HU. While limited by the absence of dosing and adherence data, this study provides proof of concept of using baseline characteristics to predict Hb response to SCD therapies, demonstrating the feasibility of a personalized treatment approach in SCD. In addition, our data provide real-world evidence of the effectiveness of HU vs. voxelotor for chronic anemia in SCD.