Form Of Hemoglobin Research Articles

Nitrosyl hemoglobin formation from nitrite in normal and sickle blood

Sickle cell anemia is caused by a single mutation in the gene encoding the beta subunit of hemoglobin. Due to this mutation, sickle cell hemoglobin (HbS) polymerizes under hypoxic conditions, decreasing red blood cell deformability and leading to multiple pathological effects that cause substantial morbidity and mortality. Several pre-clinical and human studies have demonstrated that the anion nitrite has potential therapeutic benefits for patients with sickle cell disease. Nitrite is reduced to nitric oxide (NO) by deoxygenated hemoglobin contributing to vasodilation, decreasing platelet activation, decreasing cellular adhesion to activated endothelium, and decreasing red cell hemolysis; all of which could ameliorate patient morbidities. Previous work on extracellular hemoglobin has shown that solution phase HbS reduces nitrite to NO faster than normal adult hemoglobin (HbA), while polymerized HbS reduces nitrite slower than HbA. In this work, we compared the rate of nitrite reduction to NO measured by the formation of nitrosyl hemoglobin in sickle and normal red blood cells at varying hemoglobin oxygen saturations. We found the overall rate of nitrite reduction between normal and sickle red blood cells was similar and confirmed this result under partially oxygenated conditions, but normal red blood cells reduced nitrite faster than sickle red blood cells under anoxia where HbS polymerization is maximal. These results are consistent with previous work using extracellular hemoglobin where the rate of reduction by solution phase HbS makes up for the slower reduction by polymer phase HbS under partially oxygenated conditions, but the polymer phase kinetics dominates in the complete absence of oxygen.

A critical review of therapeutic interventions in sickle cell disease: Progress and challenges.

Sickle cell disease (SCD) is an autosomal recessive genetic disorder that occurs due to the point mutation in the β-globin gene, which results in the formation of sickle hemoglobin (HbS) in the red blood cells (RBCs). When HbS is exposed to an oxygen-depleted environment, it polymerizes, resulting in hemolysis, vaso-occlusion pain, and impaired blood flow. Still, there is no affordable cure for this inherited disease. Approved medications held promise but were met with challenges due to limited patient tolerance and undesired side effects, thereby inhibiting their ability to enhance the quality of life across various individuals with SCD. Progress has been made in understanding the pathophysiology of SCD during the past few decades, leading to the discovery of novel targets and therapies. However, there is a compelling need for research to discover medications with improved efficacy and reduced side effects. Also, more clinical investigations on various drug combinations with different mechanisms of action are needed. This review comprehensively presents therapeutic approaches for SCD, including those currently available or under investigation. It covers fundamental aspects of the disease, such as epidemiology and pathophysiology, and provides detailed discussions on various disease-modifying agents. Additionally, expert insights are offered on the future development of pharmacotherapy for SCD.

Utilization and Perceptions of Hydroxyurea Therapy Among Adult Patients With Sickle Cell Disease in Al Ahsa, Saudi Arabia: A Cross-Sectional Study.

Sickle cell disease (SCD) is a prevalent genetic disorder characterized by abnormal hemoglobin formation, resulting in severe complications. Hydroxyurea (HU) therapy has demonstrated efficacy in reducing SCD-related complications; however, its utilization patterns and patient perceptions remain underexplored, particularly in the Al Ahsa region of Saudi Arabia. This cross-sectional study aimed to assess the prevalence of HU usage among adult patients with SCD in Al Ahsa; identify the barriers to starting, maintaining, and discontinuing HU therapy; and evaluate the patient-reported outcomes associated with its use. Data were collected through face-to-face surveys and medical record reviews of adult SCD patients attending outpatient clinics in the Hereditary Blood Diseases Center of Al Ahsa, Saudi Arabia, between December 2023 and March 2024. Descriptive statistics and inferential analyses were performed using SPSS version 26. A total of 345 adult SCD patients were included, with a mean age of 34.12 ± 11.1 years. Most participants were male (58.6%) and unmarried (55.4%). HU utilization was reported by 57.1% of the participants, with the highest adherence observed among older age groups (p = 0.001). Significant improvements in pain severity, hospitalization rates, and quality of life were reported among HU users (p < 0.001). Common barriers to HU use included concerns about side effects, lack of medical justification, and absence of medical advice. This study provides valuable insights into theutilization and perceptions of HU therapy among adults with SCDin Al Ahsa, Saudi Arabia. Addressing identified barriers and promoting patient education are crucial for optimizing therapy adherence and improving clinical outcomes in this population.

Hubungan Paritas Dengan Kejadian Anemia Pada Ibu Hamil di PMB Pratama Madina Medan Tembung Kabupaten Deli Serdang Tahun 2024

Anemia is a condition of hemoglobin (Hb) levels in the blood (Hb &lt;11gr/dl) caused by a lack of nutrients needed for the formation of hemoglobin. This condition causes new problems for babies, such as low birth weight, decreased immune status, possible physiological disorders, and infant growth and development. This study aims to determine the Relationship between Parity and the Incidence of Anemia in Pregnant Women at PMB Pratama Madina Medan Tembung, Deli Serdang Regency in 2024. This type of research is an analytical survey study with a cross-sectional method approach. The population is all pregnant women at PMB Pratama Madina Medan Tembung as many as 30 people. The number of samples used was 30 people obtained using the Total sampling technique. The data analysis technique used chi square. the results obtained in this study were from 30 respondents, there was a relationship between Parity and the Incidence of Anemia in Pregnant Women showing that the p value = 0.015 &lt;0.05. It is recommended for Health Workers to increase counseling related to the Incidence of Anemia in Pregnant Women.

Literature Review: the Effect of Ajwa Dates on Hemoglobin Levels in Perimenopause Women

Ajwa dates or often called prophet dates are types of dates that grow in Saudi Arabia / Al-Madinah Al-Munawara and have significant value in healing several diseases. The content of active substances contained in date extracts such as vitamins B1, B2, nicotinic acid, vitamin complex A, magnesium, calcium and iron which has a function to help the formation of hemoglobin. Perimenopause is an indefinite period of time that surrounds the final years of a woman's reproductive life, usually between the ages of 30-40 years when estrogen levels slowly decline causing menstrual abnormalities. The decrease in estrogen levels in perimenopausal women causes excessive blood loss so that iron deficiency anemia will occur. Objective : To determine the effect of consumption of ajwa dates (Pheonix Dactylifera L) on hemoglobin levels in perimenopausal women. Method : Literature Review with Design Narrative review. Results : Based on the results of research from several literatures that discuss the effects of giving Ajwa Dates (Phoenix Dactylifera L) before and after administration, it shows that there are differences in hemoglobin levels. Especially in perimenopausal women who are prone to iron deficiency anemia because Ajwa dates contain high iron, which increases hemoglobin levels. So it is highly recommended for consumption. Conclusion : Ajwa Dates (Phoenix Dactylifera L) can increase hemoglobin levels in perimenopausal women.

Compliance with Iron Supplementation Consumption in Pregnant Women on Hematological Profiles and Ret-He

Fetal growth will increase the mass of maternal and fetal erythrocytes resulting in an increase in iron requirements, causing a decrease in maternal iron stores.A decrease in iron in the body will disrupt the formation of hemoglobin, because one of the components that forms it is heme which contains iron. the aim of our research is to study the compliance of pregnant women in consuming iron supplements regarding hematological features and body iron reserves through the Ret-He examination. This research is a cross-sectional study in 30 pregnant women for complete blood count (CBC), Ret-He and estradiol. There were differences in the concentrations of Hgb and MCHC (P-value &lt; 0.05) and there were no differences in the concentrations of Hct, RBC, MCV, MCH, RDW, Ret-He and estradiol (P-value &gt; 0.05). It was found that there was a relationship between estradiol and Hgb (P-value = 0.047; r = 0.366). Pregnant women who do not comply with taking iron supplements experience a decrease in Hgb and MCHC. The decrease in Hgb levels is strongly correlated with E2 levels in pregnant women who adhere and do not comply with iron supplementation.

CORRELATION BETWEEN HEIGHT, BMI, MUAC WITH ANEMIA STATUS IN ADOLESCENT GIRLS

Background: Anemia in adolescents is a health problem that needs immediate intervention in Indonesia. Anemia can caused by malnutrition. protein and iron deficiency will cause nutritional problems including stunted, thinness, and Mid Upper Arm Circumference (MUAC) &lt; 23,5 cm. Protein and iron deficiency can interfere with the formation of hemoglobin resulting in anemia. This study aims to analyze the relationship between status based on height, Body Mass Index (BMI) and MUAC with anemia status at Mambaus Sholihin Islamic Boarding School in Gresik Regency. Method: This research is a quantitative observational analytic with the cross sectional method. The population was adolescent girls in Mambaus Sholihin Islamic Boarding School in Gresik Regency. The sample was 11th and 12th grade senior high school girls with a total of 141 respondents using the total sampling technique. The variables used in this research consisted of height, BMI, MUAC, and anemia. Height data was obtained by using microtoise, BMI using microtoise and scales, MUAC using tape measure plastic, and hemoglobin using the digital tool of Point of Care Testing (POCT) method. The research data were analyzed by chi square test with a contingency coefficient of 95%. Result: The results showed that out of 141 adolescent girls, 66.7% had normal height status, 23.4% were stunted, and 9.9% were severely stunted. In BMI status, 55.3% normal, 14.9% thinness, 15.6% overweight, and 14.2% obese. MUAC status was 79.4% with MUAC ≥ 23.5 cm and 20.6% with MUAC &lt; 23.5 cm. Anemia status was 51.8% frail and 48.2% not anemic. After the chi square test, the significance value was obtained (p=0.006), which means that statistically there was a significant relationship between height and anemia, (p=0.003) there was a significant relationship between BMI and anemia, and (p=0.01) there was a significant relationship between MUAC and anemia. Conclusion: There is a relationship between nutritional status based on height, BMI, and MUAC with anemia status in adolescent girls at Mambaus Sholihin Islamic Boarding School in Gresik Regency.

Relationship between Food and Iron Intake and Hemoglobin Levels among Medical Students: A Cross-sectional Study at Indonesian Christian University, Class of 2021

Background: Lack of protein intake will result in hampered iron transport and reduce the formation of hemoglobin (Hb). Hemoglobin is a protein compound found in red blood cells and is useful for transporting oxygen (O2) and carbon dioxide CO2 in the body. The level of protein consumption is closely related to hemoglobin, where the protein binds to iron in the body. If iron intake is lacking, it can cause red blood cell production to be disrupted and cause anemia. The world's population with anemia is around 30% or 2.20 billion people and the global prevalence of anemia is around 51%. This study was conducted to determine the relationship between iron intake and hemoglobin (Hb) levels. Aims: This research was conducted to determine the relationship between food or iron intake and hemoglobin (Hb) levels. Methodology: This research uses a descriptive-analytical research design with a cross-sectional approach and uses primary data as a research instrument, which was obtained from the results of blood sampling from students from the Faculty of Medicine, Indonesian Christian University Class of 2021 for laboratory examination using the Hematology Analyzer method and a 2x24 hour Food Recall form. The purposive sampling method was used to obtain 72 samples in this study. Results: The study showed 59 students (81.9%) were not anemic, and 13 (18.1%) were anemic. A total of 12 students (16.7%) had a low iron adequacy score, and 60 students (83.3%) had a sufficient iron adequacy score. There is a relationship between food/iron intake and hemoglobin levels (p &lt; 0.05). Conclusion: there is a significant relationship between iron intake and hemoglobin levels.

Bone Health Impairment in Patients with Hemoglobinopathies: From Biological Bases to New Possible Therapeutic Strategies.

Hemoglobinopathies are monogenic disorders affecting hemoglobin synthesis. Thalassemia and sickle cell disease (SCD) are considered the two major hemoglobinopathies. Thalassemia is a genetic disorder and one of the major hemoglobinopathies determined by an impairment of globin chain production, which causes an alteration of erythropoiesis, an improvement in hemolysis, and an alteration of iron homoeostasis. In SCD, the mutations are on the β-globin chain of hemoglobin which results in a substitution of glutamic acid by valine with consequent formation of Hemoglobin S (HbS). Several factors are involved in bone metabolism alteration in patients with hemoglobinopathies, among them hormonal deficiency, bone marrow hyperplasia, iron overload, inflammation, and increased bone turnover. Bone metabolism is the result of balance maintenance between bone deposition and bone resorption, by osteoblasts (OBs) and osteoclasts (OCs). An impairment of this balance is responsible for the onset of bone diseases, such as osteoporosis (OP). Therefore, here we will discuss the alteration of bone metabolism in patients with hemoglobinopathies and the possible therapeutic strategies to contain and/or counteract bone health impairment in these patients, taking into consideration not only the pharmacological treatments already used in the clinical armamentarium, but also the new possible therapeutic strategies.

Enhancing Maternal Health: IT Solutions for Monitoring Anemia in Pregnancy

Background: Anemia is a condition in which a deficiencyof red blood cells (erythrocytes) in the blood cycle or mass of hemoglobin is so unable to fulfill its function as a carrier of oxygen in the entire tissue. Handling to increase hemoglobin levels by using pharmacological and non-pharmacological management, one of the non-pharmacological management is by giving vitamin C so that the process of absorption and formation of hemoglobin is faster such as consuming red guava juice every day 2 x 1 together with Fe. the study was to determine the effect of giving Fe tablets and red guava juice on increasing hemoglobin levels in third trimester pregnant women. This pre-post experimental research design uses a design pretest-posttest whit control group design. The sampel in this study 36 respondents consisting of 18 experimental respondents and 18 control respondents with purposive sampling technique. The research instrument used the measuremets tool HB Family Dr. Test Strip and observation for 2 weeks. Data were analyzed using paired t-test to determine changes before and after and independent T-Test to determine the difference between the experimental group and the control group. The results of the pre-post study in the experimental group were p values of 0,000(p &lt;0.05) and in the control group were 0.01(p &lt;0,05). The results of the pre-post study in the experimental and control group p value 0,000. There is an effect of giving red guava juice and Fe tablets to increase hemoglobin levels of pregnant women in the third trimester who have mild anemia. Therefore, it is hoped that PMB (Praktek Mandiri Midwives) can pay attention to the handling of anemia in pregnant women in Kedaung, Pamulang, Tangerang. South with outreach programs and supplementation such as giving red guava juice.

Impact of Mar’ke Bilar Healthy Drink on Blood Levels of Malondialdehyde, Superoxide Dismutase, and Hemoglobin in Soccer Athletes at PPLP North Sumatra

Background: High-intensity soccer activities due to overtraining can cause the emergence of reactive oxygen species (ROS), resulting in an imbalance of free radicals in the form of malondialdehyde (MDA) and endogenous antioxidants in the form of superoxide dismutase (SOD). As a result, it can interfere with the formation of hemoglobin (Hb) needed by an athlete to take in oxygen (VO2max). Objectives: This study was designed to determine the effect of giving a healthy drink Mar’ke Bilar on MDA, SOD, and Hb levels in soccer athletes at PPLP North Sumatra, Indonesia. Methods: This type of research is quasi-experimental with a one-group pre- and post-test design. The population and research samples amounted to 33 soccer athletes at PPLP North Sumatra. The administration of Mar’ke Bilar as much as 200 ml was carried out for 14 days, and then MDA, SOD, and Hb levels were measured before and after. A normality test was conducted with the Kolmogorov-Smirnov test, followed by a different test using a paired t-test. Results: Malondialdehyde levels decreased from 17.5 to 10.9 µmol/L. There was an increase in SOD from 45.945 to 53.256 pg/mL. However, the results of Hb also showed an increase from 14.3 to 15.1 gr/dL. There was a significant effect on levels of MDA (P = 0.001), SOD (P = 0.001), and Hb (P = 0.002). Conclusions: Mar’ke Bilar healthy drink consumption has an effect on reduced MDA levels and increased SOD and Hb.

The Effect of Giving Dates (Phoenix dactylifera) on Hemoglobin Levels in Anemic Adolescent Girls at Prima Nusantara Vocational School, Bukittinggi, Indonesia

Anemia in adolescent girls is a health problem that often occurs in Indonesia. Dates (Phoenix dactylifera) is a fruit that is rich in iron and folate, which play an important role in the formation of hemoglobin. This study aims to determine the effect of giving dates on hemoglobin levels in anemic adolescent girls at Prima Nusantara Vocational School, Bukittinggi Indonesia. This research used a quasi-experimental design with a pretest-posttest with the control group design. A total of 30 adolescent girls who experienced anemia were randomly divided into two groups, namely the intervention group which was given 3 dates per day for 4 weeks and the control group which was given no dates. Hemoglobin levels were measured before and after the intervention. The results showed that there was a significant increase in hemoglobin levels in the intervention group compared to the control group (p &lt; 0.05). Giving dates can increase hemoglobin levels in adolescent girls who suffer from anemia.

Sari Kedelai Kurma Meningkatkan Kadar Hemoglobin Pada Remaja Putri

Anaemia often occurs in teenagers and young women due to nutritional problems. Iron, which is found in food nutrients, plays a significant role in the formation of haemoglobin. Soybeans and dates are some of the foods that contain high iron to elevate haemoglobin levels in the blood. Soybeans dan dates Juice is a drink that circulating and become popular in Indonesia. This study used the Pre-Experimental research type with a Group Pre-Post Test Design approach. Accidental sampling was used to select 18 respondents. The Paired T-test was used for data analysis. Before the participants were given date soybean juice, the average haemoglobin level in 18 respondents was 13.81 gr%. After drinking date soybean juice for six days, the haemoglobin level increased to 15.45 gr%. The difference in average before and after giving date soybean juice was 1.46 gr%. The results of the statistical tests with the Paired T-Test show a p-value of 0.001 &lt; α = 0.05. This test concludes that Ha is accepted, which shows that giving date soybean juice has a positive effect on increasing haemoglobin levels in young women at Baitul Hikmah Tempurejo Vocational School. Therefore, young women should consider consuming date soybean juice to prevent anaemia.

Korelasi Pola Asupan Protein Dan Zat Besi Dengan Kadar Hemoglobin Pada Mahasiswi Prodi Kedokteran Universitas Khairun

Iron Deficiency Anemia (IDA) is anemia with the cause being a decrease in the amount of iron needed in the process of erythropoiesis due to depleted iron stores, causing a decrease in hemoglobin formation. Riskesdas data in 2018 stated that in 300,000 households, women experienced more anemia (27.2%) than men (20.3%). The anemia rate among 15-24 year olds reached 32% in 2018. Knowing the correlation of protein and iron intake patterns with hemoglobin levels in Khairun University Medical Study Program students. This research is an analytic study that uses a cross-sectional approach. The research sample was female students who met the inclusion criteria and were determined using purposive sampling technique. Data on protein and iron intake patterns were collected through interviews using the 24-hour food recall method taken twice. Data on hemoglobin levels were obtained from collection with a portable Hb meter. In 109 samples, the most common results were deficient protein intake (78.0%), deficient iron intake (75.2%), and normal hemoglobin (72.5%). and methodology are arranged in the form of past tense, while the results and conclusions in the form of simple present tense.

Importance of Iron:

Iron plays a crucial role in the formation of hemoglobin, which carries oxygen throughout the body. Iron deficiency, causing anemia in teenagers, can result in fatigue, decreased concentration, and even decreased immunity. The prevalence of anemia in Indonesia is high, especially among adolescent girls. Anemia can affect study concentration and productivity. Adolescents' learning concentration is influenced by various factors, including insufficient iron intake. Therefore, this counseling aims to increase understanding of the importance of iron in maintaining energy balance and concentration at school, reducing the impact of anemia on adolescent well-being. These extension activities apply an educational and preventive approach. By providing clear information about the role of iron, the consequences of deficiency, and the impact of anemia, an educational approach is used to increase students' understanding. Anemia education has succeeded in increasing students' understanding of the causes, symptoms, impacts and prevention of anemia. The students' active participation during the session marked a high level of engagement. The conclusion shows that this activity not only provides knowledge, but also increases students' awareness of the link between their health and academic achievement.

Treatment of sickle cell anemia using CRISPR and prime editing

Sickle cell disease is a hereditary blood disease caused by an invisible genetic mutation on the autosome, caused by a transversion mutation in which the 6th amino acid of the -peptide chain, glutamate, is replaced by valine, resulting in the formation of sickle hemoglobin, instead of normal hemoglobin. Due to genetic mutations leading to structural abnormalities in hemoglobin and morphological changes in red blood cells, red blood cells lose their deformability in hypoxic environments, leading to vascular blockage, causing severe pain and partial tissue ischemia in patients. Oxygen needs to be transported to various parts of the body through red blood cells, thereby affecting the transportation of oxygen in the body. In general, red blood cells are circular and elastic, making them easy to move in blood vessels. However, in sickle cells, these red blood cells are compressed and deformed, causing the transportation of oxygen in the blood to become stiff and viscous, potentially slowing or blocking blood flow. The most common complication of SCA is blockage of blood vessels, which leads to pain. Although this is a complex phenomenon, HbS aggregation is a fundamental pathological physiological phenomenon in SCA. HbS aggregation can lead to malignant changes in the shape and physical properties of red blood cells, leading to hemolytic anemia and preventing blood flow, especially in small blood vessels, which may damage some organs. Clinical manifestations include anemia, immunodeficiency, multiple organ damage, severe acute and chronic pain, and premature death. The quality of life of the patients was seriously affected.

Inhibition of amyloid formation of bovine hemoglobin by bioactive phenolic acids: an elaborate investigation into their binding properties with the protein using multi-spectroscopic and computational techniques

Interactions of bioactive phenolic acids with BHb were investigated using spectroscopic methods along with their inhibitory potential against bovine hemoglobin amyloid formation in vitro.

Novel bioanalytical strategy using isotope pattern deconvolution and ICP-QMS for the study of iron incorporation in erythrocytes: An insight to better assessment

Iron is an essential element for human life and its nutritional status in the human body is directly linked to human health. More than 1015 atoms of iron per second are necessary for the maintenance of haemoglobin formation. To predict iron bioavailability three approaches are normally employed: (a) faecal recovery; (b) plasma appearance; and (c) erythrocyte incorporation (the most used). Isotope Pattern Deconvolution (IPD) is a mathematical tool that allows the isolation of distinct isotope signatures from mixtures of natural abundance and enriched tracers. In this work we propose a novel strategy to assess erythrocyte iron incorporation, based on the use of an iron stable isotope (57Fe) and the IPD concept. This strategy allows direct calculation of the exogenous concentration of 57Fe incorporated into RBCs after supplementation. In this way, to determine the mass of iron incorporated into erythrocytes, the unique prediction that must be made is the blood volume, estimate to reproduce the natural dilution of the tracer (57Fe) in the blood. This novel bioanalytical approach was applied for the measurements of iron incorporation and further iron absorption studies in humans, using a group of twelve healthy participants, that should be further evaluated for the assessment of other chemical elements that could be of health concerns and directly impact society.

Pyruvate Kinase Thermostability Is Associated with Red Blood Cell Adhesion, Deformability and Oxygen Affinity in Patients with Sickle Cell Disease

Introduction: Sickle cell disease(SCD) is caused by a mutation in the beta globin gene that causes formation of abnormal hemoglobin S (HbS). Red blood cells (RBCs) from patients with SCD are less deformable and take on the shape of sickle upon deoxygenation. This results in multiple downstream effects including RBC adhesion, microvascular occlusion and chronic hemolysis. RBCs rely solely on anaerobic glycolysis to produce adenosine triphosphate (ATP), which is needed to maintain the cell's structure and function. Pyruvate kinase (PK) is a key enzyme involved in the last step of glycolysis. We have previously demonstrated a decrease in PK activity and stability as a novel pathophysiological feature of SCD. Currently there are several clinical trials ongoing investigating the efficacy of PK activation by small molecules such as mitapivat (NL8517, NCT04000165, NCT05031780), AG-946 (NCT04536792) and etavopivat (NCT04624659, NCT04987489). In this study we aim to investigate how PK properties correlate to sickle RBC properties in order to explore if impaired PK function is associated with specific features of the complex SCD pathophysiology. Methods: Homozygous HbS (HbSS) and HbS/ β0 thalassemia patients were eligible to participate. Patients who received blood transfusion (&amp;lt;3 months) were excluded. Dense RBCs (MCHC &amp;gt;41 g/dL, Advia 120/2120 Siemens) and HbF and HbS levels (Tosoh G8) were measured. PK and hexokinase (HK) activity were measured on purified RBCs. PK thermostability (reflected by % residual PK activity) was measured on purified RBCs lysates after one hour of incubation (53°C). RBC adhesion to laminin (Biolamina) was measured using a microfluidic device (IBIDI µ-Slide I 0.4). RBC hydration (Ohyper), RBC deformability (EImax) and point of sickling (PoS) were assessed by osmotic and oxygen gradient ektacytometry using the Laser-Optical Rotational Red Cell Analyzer (Lorrca, RR Mechatronics). Oxygen affinity (P50) was measured with the Hemox-Analyzer (TCS). Statistical analysis was performed in Graphpad Prism (Pearson's correlation). Results: Fifty-seven patients with SCD (53 HbSS, 4 HbS/β 0 thalassemia) were included of which 17 were children (median age 14 years [range 6-17]) and 40 were adults (median age 36 years [range 18-58]). Baseline characteristics are depicted in Table 1. Figure 1 shows a heatmap with correlation coefficients of all laboratory parameters from Table 1 as measured in this cohort. When focusing on PK properties we found that patients with SCD and lower PK thermostability had significantly higher absolute reticulocyte counts (ARC, p&amp;lt;0.0001), lower hemoglobin (p=0.012) and HbF (p=0.020) levels and increased RBC adhesion to laminin (p=0.007). Furthermore, PK thermostability was significantly correlated with EImax (p=0.017) and inversely correlated with PoS (p=0.011) and P50 (p=0.003), indicating that patients with less stable RBC PK had less deformable RBCs which sickled at a higher oxygen tension. RBC adhesion to laminin was significantly correlated with both ARC (p=0.0003) and dense RBCs (p=0.019). To explore whether our findings were a reflection of reticulocytosis we fractionated whole blood samples of HbSS patients according to cell density. We found that more RBCs from the most dense fraction adhered to laminin than from the less dense, reticulocyte enriched, fraction, even though RBCs from this less dense fraction had reduced PK-thermostability. Additionally, the most dense RBCs had the lowest PK activity, were less deformable and had a higher PoS (data not shown). Altogether these findings indicate that the reduced PK thermostability we found in our SCD cohort is associated with an overall functionally impaired RBC population with increased RBC adhesion and ARC. We found no correlation of markers of RBC dehydration (Ohyper and % dense RBCs) with PK thermostability which suggests that RBCs with reduced PK thermostability are not more dehydrated. Discussion/conclusion: This study shows for the first time a significant correlation between PK thermostability in sickle RBCs and RBC functions, such as adhesion, deformability and oxygen affinity. Our results suggest that enhancing the activity and stability of PK, with PK activators, is an attractive target in SCD that might improve other pathophysiological targets outside RBC metabolism. Future studies are needed to explore how activation of PK will affect these altered sickle RBC properties in vivo.

Sickle Cell Trait As a Risk Factor for Leukemia: A Nationwide Study

INTRODUCTION: Leukemia is a cancer of blood-forming cells. It can arise from cells of lymphoid or myeloid lineage. It can arise from genetic mutations in tumor suppressor genes, proto-oncogenes or both. It affects over two million people worldwide. A combination of genetic factors and extrinsic factors are believed to play a role. Sickle cell disease (SCD), an inherited disorder leading to the formation of abnormal hemoglobin (HbS) and red blood cell sickling, has been shown to increase the risk for leukemia, presumably due to an increased bone marrow turnover rate. We aimed to explore if sickle cell trait (SCT), when people inherit only one of the two sickle cell genes, is associated with an increased risk for leukemia. METHODS: In this case-control study, we evaluated an association between leukemia (and its subtypes) and SCT in a nationwide cohort of hospitalized patients included in the National Inpatient Sample (NIS) 2016-2019 database. The inclusion criteria for cases were patients who had any of the following ICD-10-CM codes for leukemia: C91 (lymphoid leukemia), C92 (myeloid leukemia), C93 (monocytic leukemia), C94 (other leukemia of specified cell type), and C95 (leukemia of unspecified cell type). The exclusion criteria were Down syndrome (Q90), Fanconi anemia (D61.09), ataxia-telangiectasia (G11.3), Bloom syndrome (Q82), myelodysplastic syndrome (D46), lymphoma (C81, 85), and solid malignancies (C00-75) as these diseases and/or their treatments are known to increase the risk for leukemia independently of SCT (ICD-10-CM D57.3). The controls included patients in the NIS database who do not have the ICD-10-CM codes for leukemia and meet the exclusion criteria applied to the cases. For each year, we used a 1:4 propensity score matching routine. Our match variables were sex, the six race categories used by NIS, and 11 age groups. Four perfect matches (controls) were identified for each case (‘any leukemia’ diagnosis). Patient characteristics were compared using Pearson chi-squared test. Odds ratios (ORs) were calculated for ‘any leukemia’ diagnosis, as well as for each subtype of leukemia. Five multivariate logistic regression models were used to examine the relationship between the leukemia subtypes and SCT while controlling for age group, sex, and race. RESULTS: We identified 181,676 cases and 726,704 controls. The mean age of subjects was 59 years. The majority of subjects (56%) were male. A greater proportion of patients with SCT were found among cases (0.12%) compared to controls (0.08%) (p &amp;lt; 0.0001). The OR for ‘any leukemia’ was 1.48 (95% CI 1.27-1.73, p &amp;lt; 0.0001). When the association between SCT and specific subtypes of leukemia was evaluated, it was statistically significant for myeloid and monocytic leukemias, OR 1.74 (95% CI 1.40 - 2.17) and 2.20 (95% CI 1.09 - 4.42) correspondingly. CONCLUSION: Our case-control study revealed statistically significantly higher odds of SCT among patients with any leukemia (and specifically myeloid and monocytic leukemias) as compared to controls which can be postulated to the common myeloid progenitor lineage of erythrocytes. Our results suggest that, similarly to SCD, SCT although a benign condition can increase the risk for leukemia. To better understand this association, future prospective studies are needed for the mapping of individual risk factors and examining the HbS% levels in SCT carriers who go on to develop leukemia.