Hemoglobin Synthesis Research Articles

Global profile of anemia during pregnancy versus country income overview: 19 years estimative (2000–2019)

Anemia is a worldwide public health problem that is worst in low- and middle-income countries (LMICs), reaching 60% of prevalence. The etiology of anemia is diverse and multifactorial, with iron deficiency being the most prevalent, and often found in pregnant women. Iron is indispensable for the production of red blood cells and approximately 80% of the available heme iron is used for hemoglobin synthesis in mature erythroblasts. Iron deficiency affects oxygen transport, compromising energy and muscle metabolism and can occur with depletion of iron storage, defective erythropoiesis, and low hemoglobin levels. We analyzed anemia prevalence in pregnant women from 2000 to 2019 worldwide correlating them with current (2022) country income, with especial attention to LMICs using WHO dataset. Our analysis indicates that pregnant women from LMICs had a higher probability (40%) of anemia during pregnancy especially those from Africa and South Asia. Africa and the Americas showed a higher decrease in the prevalence of anemia from 2000 to 2019. The Americas and Europe have a lower prevalence, concentrated in 57% of most upper-middle- and high-income countries. Black women are also more prone to develop anemia during pregnancy, especially if they are from LMICs. However, the prevalence of anemia appears to decrease with an increase in educational level. In conclusion, anemia prevalence fluctuated from 5.2 to 65.7% worldwide in 2019, validating it as a public health problem.

A Rare Case: HaemoglobinS-Thalassemia in Adult

Hemoglobinopathy refers to a disease involving a qualitative or quantitative defect of the structure or synthesis of haemoglobin molecules. The HaemoglobinS- beta thalassemia occurs in a heterozygotes individual with beta-thalassemia and HaemoglobinS gene. A 29-year-old man came with severe anemia, thrombocytopenia, and history of repeated blood transfusions. Physical examination showed pale conjunctiva, pansystolic murmurs, and hepatosplenomegaly. The HaemoglobinS fraction was found in haemoglobin electrophoresis with increased HaemoglobinF and decreased HaemoglobinA2 fraction. The peripheral blood smear shows abnormal erythrocytes morphologies such as pencil shapes, fragmentocytes, target cells, and sickle shapes. The patient was diagnosed with chronic anaemia caused by HaemoglobinS-beta thalassemia. It makes ineffective erythropoiesis, intravascular, and extravascular hemolysis. This haemoglobinopathy caused increased ferritin and transferrin saturation. The presence of renal failure indicate there is a complicated condition like microvascular obstruction of renal. In this case, there is a reduction of HaemoglobinA2 fraction that is not common in HaemoglobinS-beta thalassemia. The patient with Haemoglobin S / beta+ thalassemia shows intravascular hemolysis, ineffective hematopoiesis, and vaso-occlusive signs. Deoxyribo Nucleic Acid analysis is further needed to confirm the combination defect of haemoglobin synthesis disorders in conjunction with alpha thalassemia or Hereditary persistence of fetal haemoglobin.

Genetic heterogeneity of thalassemia major patients in Rembang Regency, Central Java, Indonesia

Link of Video Abstract: https://www.youtube.com/watch?v=RG95aJkUndg Background: Thalassemia and hemoglobinopathies are caused by mutations in the globin genes that reduce haemoglobin synthesis. In many Asian countries, including Indonesia, thalassemia is a common inherited disorder. Thalassemia has specific characteristics due to the wide variability of the mutations from various populations. Therefore, screening protocol should be designed on specific populations’ regional gene mutation patterns. This study aims to investigate the mutational diversity of the globin genes in thalassemia major patients in Rembang Regency, Central Java, Indonesia. Methods: Genetic mutations were carried out in all major thalassemia patients who were recorded and underwent routine blood transfusions at the Rembang District Hospital from 2018 – 2020. Mutation identification was carried out using a PCR- RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) based method, the ACRS (Amplified Created Restriction Site) method, and genome sequencing. Results: The most common genotypes are double heterozygous HbE and Cd 35 mutation (-C) (42.87%), HbE and IVS1-nt.5 mutations (G> C) (28.57%), HbE and IVS1- nt.2 mutations (T> C), HbE and codon 8/9 (insertion + G), codon 8/9 (insertion + G) and Hb Malay, as well as Hb Adana and Hb Constant Spring (1.74%). Conclusion: The β-thalassemia and α-thalassemia mutations most commonly found in Rembang Regency are Cd 35 (-C) and non-deletional mutations.

Drugs activating hypoxia-inducible factors correct erythropoiesis and hepcidin levels via renal EPO induction in mice

AbstractThe erythroid growth factor erythropoietin (EPO) is mainly produced by the kidneys in adult mammals and induces expansion of erythroid cells and iron use for hemoglobin synthesis. The liver also produces EPO at a lower level than the kidneys. Renal and hepatic EPO production is fundamentally regulated by hypoxia-inducible transcription factors (HIFs) in a hypoxia/anemia-inducible manner. Recently, small compounds that activate HIFs and EPO production in the kidneys by inhibiting HIF-prolyl hydroxylases (HIF-PHIs) have been launched to treat EPO-deficiency anemia in patients with kidney disease. However, the roles of the liver in the HIF-PHI–mediated induction of erythropoiesis and iron mobilization remain controversial. Here, to elucidate the liver contributions to the therapeutic effects of HIF-PHIs, genetically modified mouse lines lacking renal EPO-production ability were analyzed. In the mutant mice, HIF-PHI administration marginally increased plasma EPO concentrations and peripheral erythrocytes by inducing hepatic EPO production. The effects of HIF-PHIs on the mobilization of stored iron and on the suppression of hepatic hepcidin, an inhibitory molecule for iron release from iron-storage cells, were not observed in the mutant mice. These findings demonstrate that adequate induction of EPO mainly in the kidney is essential for achieving the full therapeutic effects of HIF-PHIs, which include hepcidin suppression. The data also show that HIF-PHIs directly induce the expression of duodenal genes related to dietary iron intake. Furthermore, hepatic EPO induction is considered to partially contribute to the erythropoietic effects of HIF-PHIs but to be insufficient to compensate for the abundant EPO induction by the kidneys.

Beta thalassemia revealing hypothyroidism: A case report

Thalassemia is a condition that affects hemoglobin synthesis and is one of the most Common hereditary illnesses in the world. Patients with thalassemia major require several blood transfusions. Multiple blood transfusions cause thyroid dysfunction, which leads to iron excess. We report the case of 35-year-old, followed in hematology for deep iron deficiency anemia who has benefited from a transfusion repeatedly diagnosed with beta thalassemia. At the interrogation, the patient reports a moderate gain of weight not quantified, hair loss and sensations of chills, chronic constipation, without other associated signs including no other signs of hypersecretion or anterior pituitary hyposecretion, no tumor SD. The physical examination finds a conscious patient, Normocardium, normal build, dysmorphic SD, palpable thyroid not increased in size. Microcytic hypochromic anemia, TSH at 10 mIU/l (0.35 -5.1) mIU / l, T4 at 10.6 pmol / l (10.6-19.4) pmol / l T3 to 2.88 pmol / l (3.8-8.4) pmol / l. Objective cervical ultrasound thyroid gland increased in size at the expense of the thyroid lobe with thyroid nodules classified EU-TIRADS 2 and 3. The patient was put on levothyrox 75ug/d. Thyroid disorders are common in β-thalassemia patients who have been transfused multiple times.

Assessment of Liver Functions in Thalassaemia

Thalassaemias are a heterogenous group of genetic heritable disorders of haemoglobin synthesis, considered as the most common monogenic disorder in the world. This study was conducted to find out the role of iron overload- without concomitant viral hepatitis -as a cause of liver dysfunction in patients with β-thalassaemia major. One hundred six (106) patients with homozygous β-thalassaemia major and forty four (44) apparently healthy subjects were analyzed at the Thalassaemic Centre of Ibn Al-Atheer hospital in Mosul city in Iraq for the assessment of liver functions as reflected by the serum levels of bilirubin, AST, ALT and ALP and iron status as reflected by serum ferritin. The mean pretransfusional Hb was (87.33±13.84 g/L and 85.85±13.21 g/L) for thalassaemic males and females respectively. All thalassaemic patients showed elevated serum ferritin with a mean level of (3799.30±2343.68 ng/ml and 4100.61±1977.28 ng/ml) for thalassaemic males and females respectively. A significant increase in the serum levels of AST, ALT, ALP and bilirubin was found in thalassaemic patients with respect to control subjects. Serum ferritin showed a significant positive correlation with ALT in male and female patients. Hepatomegaly was found in 71.70% of the studied cases. A significant alteration in liver functions of thalassaemic patients shown by changes in biochemical markers and hepatomegaly, both with the close association between elevated ALT and iron overload, necessate re-evaluation of transfusion, Desferal doses and therapies other than blood transfusion.

Peningkatan Kualitas Hidup Anak Thalasemia Pada Masa Pandemi Covid-19

Thalassemia is a disorder of hemoglobin synthesis with clinical manifestations of severe anemia. With a total of 35 sufferers in North Lampung, thalassemia causes complex health problems, especially during the Covid-19 Pandemic, including 1. The limited blood supply for transfusions due to decreased donors; 2. The problem of malnutrition leading to reduced immunity; 3. Psychological and school problems; 4. Not all thalassemia children in North Lampung had Hb-analysis as a diagnostic procedure; and 5. Low consumption of iron chelation drugs to prevent hemosiderosis. The community service aims to improve the quality of life for thalassemia children in North Lampung during the Covid-19 Pandemic. The Community service activities used a process approach (preparation, implementation, evaluation) involving several professions and related stakeholders (interprofessional collaboration). The target of the activities was thalassemia children and families who are members of the Association of Parents with Thalassemia (POPTI) North Lampung, with a total of 35 people. Data were analyzed with proportional descriptive analysis. The community service activities were 1. Formation of a Thalassemia Care Community consisting of 75 permanent blood donor volunteers; 2. Health education about the nutritional needs of thalassemia children and provision of nutrition packages to 33 people (94.28%); 3. Counseling on psychosocial problems and learning disorders in schools; 4. Facilitating story books in the treatment room of HM Mayjend Ryacudu Hospital; 5. Laboratory examination of Hb analysis and ferritin levels and socialization of the management of iron chelation treatment to 23 people (65.71%) of thalassemia children and their families. All activities were carried out with health protocols during the Covid-19 Pandemic. Suggestion: It is necessary to develop a network and increase the membership of the Thalassemia Care Community to six permanent donors for one thalassemia child. The Originality/Value/ Implication of this community service activity is the formatting of the North Lampung Thalassemia Care Network and Community.

Cryo-EM structures of mitochondrial ABC transporter ABCB10 in apo and biliverdin-bound form

ABCB10, a member of ABC transporter superfamily that locates in the inner membrane of mitochondria, plays crucial roles in hemoglobin synthesis, antioxidative stress and stabilization of the iron transporter mitoferrin-1. Recently, it was found that ABCB10 is a mitochondrial biliverdin exporter. However, the molecular mechanism of biliverdin export by ABCB10 remains elusive. Here we report the cryo-EM structures of ABCB10 in apo (ABCB10-apo) and biliverdin-bound form (ABCB10-BV) at 3.67 Å and 2.85 Å resolution, respectively. ABCB10-apo adopts a wide-open conformation and may thus represent the apo form structure. ABCB10-BV forms a closed conformation and biliverdin situates in a hydrophobic pocket in one protomer and bridges the interaction through hydrogen bonds with the opposing one. We also identify cholesterols sandwiched by BVs and discuss the export dynamics based on these structural and biochemical observations.

Therapeutic Phlebotomy Revisited: A Review

Therapeutic phlebotomy is the removal of red blood cells or serum iron from the blood. It is one of the preferred treatments for blood disorders. In ancient times this process was known as bloodletting. Generalized method included were venesection and arteriotomy and systemic methods included were cupping and by leeches. It stimulates bone marrow stem cells to generate new red blood cells (RBCs). Iron for hemoglobin synthesis is taken from the body thus reducing serum iron. Different indications of therapeutic phlebotomy include Polycythemia Vera, Hemochromatosis, Porphyria cutanea tarda, Sickle cell disease, Non-Alcoholic Fatty liver disease (NAFLD) with hyperferritinemia. Other methods available for reducing RBC and iron level include apheresis and administration of desferroxamine. Phlebotomy can cause rare adverse effects, such as thrombosis, mostly seen in patients with polycythemia Vera. Other adverse effects include Hematoma at phlebotomy site. Usually hematoma is mild but in severe cases can cause damage in nerves and surrounding tissue. Haemoconcentration, extravasation, Syncope and Fainting, petechiae, Excessive Bleeding, edema, arterial puncture, pain and anemia are some of the adverse effects caused by therapeutic phlebotomy. Unsafe phlebotomy can expose patients and health workers to various infections like Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Human Immunodeficiency virus (HIV); syphilis and malaria. Different countries have approved allogenic use of blood units obtained from therapeutic phlebotomy. Mostly blood collected from patients with hemochromatosis is permitted. The article also discusses criteria for initiating therapeutic phlebotomy and various regimen followed in different diseases.

Evaluation of Gait in Albanian β-thalassemia Patients

Abstract One of the most prevalent genetic diseases in the world is beta thalassemia. Hemoglobin synthesis is decreased by the blood condition beta thalassemia. Patients with thalassemia exhibit a range of bone problems, including as spinal deformities, osteopenia and osteoporosis, as well as growth failure. This study’s main goal was to evaluate gait and balance in Albanian β-thalassemia patients. In this study, 18 participants aged 17 to 29 years old (5 males and 13 females) from three distinct epidemiological cities in Albania took part. Gait analysis was performed using “T&T medilogic medizintechnik gmbh” wi-fi insoles. “General Gait Parameters”, results of the “Effective Foot Length, left [%]” parameter mean results [67.59%], reveals approx a 2% difference compared with the relative normative mean [69.7%]. Also, “Effective Foot Length, left [%]” mean results [65.49%], reveals approximately a 3.5% difference compared with the relative normative mean [69.7%]. “General Gait Parameters”, data comparisons revealed statistically significant differences between “is” and “nom.” measurements for the following variables: “Rel Double Step Length”, “Double Step Duration”, “Effective Foot Length Right” and “Width Of Gait Right” (p<0.005). Results for the rest of the variables shwed a not statistically significant difference. The aim of the study was to assess the gait parameter in Albanian individuals with thalassemia. Based on the result of the “General Gait Parameters”, data reveal a difference in the % of the average gait line which is related to effective distribution in the insole length showing a specific indication of insecure gait. According to the findings, gait issues are a significant health issue for beta thalassemia patients which are most likely caused by disease-related side-effects such high calcium levels after blood transfusions, inactivity caused by insufficient muscle mass, and all other health-related disease conditions. It is advised that the gait analysis exam to be included in their regular health check-ups. Future studies should be conducted involving larger ß-thalassemia patients take into account the unique state of this category to better evaluate the gait problems related with general static and dynamic posture problems. Clinicians’ health specialists and rehabilitation experts when planning B-Thal rehabilitation programs sholud use gait analysis exam as a regular health check-up.

5597164 BURDEN AND RISK FACTOR TO ACUTE MYOCARDIAL ISCHAEMIA IN CHILDREN WITH SICKLE CELL ANAEMIA

Introduction: Sickle cell anaemia (SCA) is a genetic disorder of haemoglobin synthesis with multi-organ manifestations. Myocardial ischaemia (MI) and infarction as a result of sickling are not commonly reported, often overshadowed by the more dramatic presentation of musculoskeletal pain. Studies have postulated that sudden deaths during vaso-occlusive crisis (VOC) may be secondary to the arrhythmogenic effect of severe MI. Aim: This study compared the prevalence of MI and associated risk factor in children with SCA aged 6 months to 18 years in VOC and steady state at the Lagos University Teaching Hospital using both cardiac troponin T (cTnT) and electrocardiography (ECG) as recommended by the fourth universal definition of MI (2018). Methodology: A cross-sectional comparative study conducted over 10months (March and December 2019). The participants were 250 children (125 age and gender-matched children with SCA in VOC and steady state respectively). Informed consent was obtained from the parents or caregivers while assent was obtained from children 10 years and above. Socio-demographic data and relevant history were obtained using an interviewer-administered questionnaire. Targeted clinical examination with focus on the cardiovascular system was done. All study participants had ECG performed and blood samples taken for cTnT, full blood count, electrolyte, urea, and creatinine. Myocardial ischaemia was defined as cTnT level greater than 100ng/L which is the 99th percentile and abnormal ECG findings indicative of MI (wide Q wave, ST-segment elevation or prolonged QT interval corrected for heart rate with accompanying Q wave abnormalities). Statistical package for social sciences (SPSS) software version 20 was used for analysis, statistical association was declared significant if the p-value was <0.05. Results: The prevalence of MI using cTnT alone in children with SCA in VOC and steady state was 42.4% (53) and 23.2% (29) respectively while with ECG alone, the prevalence of MI in children with SCA in VOC and steady state was 40.8% (51) and 20.8% (26) respectively. The prevalence of MI using both cTnT and ECG in children with SCA in VOC and steady state was 38.4% and 20% respectively and this was statistically significant (p-valve 0.001). In relation to VOC, the mean age (10.0±4.1), mean WBC (20,131.2±7,268.0), mean platelet count (461,208.0±143,956.8) and pain score of children with MI was significantly higher compared to those without MI. Among the steady state children, higher mean age (11.6±3.5), lower mean PCV (22.3±3.7) and higher mean platelet count (446,240.0±140,841.0) was significant in children in steady state with MI compared to those without MI. Furthermore, on multivariate analysis, the mean age & mean platelet count; mean age & low PCV; were significantly associated with MI in children with VOC and steady state respectively. The older age group in both study participants had a higher prevalence of MI. Combining both cTnT and ECG in the diagnosis of MI gave similar prevalence compared to using either cTnT or ECG alone. Conclusion: Myocardial ischaemia (MI) is prevalent in children with SCA. Children with SCA should routinely be screened for MI during VOC and steady state especially adolescents with SCA for early intervention.

Iron deficiency in sepsis patients managed with divided doses of iron dextran: a prospective cohort study

Iron deficiency (ID) impairs hemoglobin (Hb) synthesis and immune function, both crucial for sepsis patients. We assessed the impact of iron dextran on reticulocyte (Ret) Hb equivalent (Ret-He) and Ret subpopulations in iron-deficient sepsis patients. In this prospective clinical study we enrolled patients with sepsis or septic shock with procalcitonin concentration > 0.5 ng/mL, diagnosed with ID based on Ret-He. Study subjects received divided doses of iron dextran until normalization of Ret-He. The study population included 35 subjects. The median Ret-He increase after 2 doses of iron dextran was 3.0 (IQR 1.9–6.1) pg (p < 0.01) with median time to normalization 4 (IQR 3–5) days. Although no change in Ret percentage [Me 1.5 (IQR 1.1–2.1) vs. Me 1.4 (IQR 1.1–2.4) %, p = 0.39] and number [Me 0.05 (IQR 0.04–0.07) vs. Me 0.05 (IQR 0.03–0.06) 106/µL, p = 0.88] was noted, Ret subpopulations changed significantly (p for all < 0.01). Divided doses of iron dextran relatively quickly normalize Ret-He in iron-deficient sepsis patients. Changes in Ret subpopulations suggest increased erythropoietic activity. Further research is needed to explore the role of intravenous iron in this clinical setting.

Productivity of pigs under the conditions of introduction of the additive of the mixed ligand complex of Cuprum

The intensification of the pig industry requires the breeding of highly productive young animals capable of providing high-growth energy under good conditions of maintenance and full feeding. Full feeding of suckling piglets in most farms of Ukraine is provided by pre-starter compound feeds of imported production, which leads to an increase in the cost price of pork. In addition, the traditional sources of trace elements in these compound feeds are mineral salts in the form of sulfate and chloride compounds, the bioavailability of which is 12–35 %, which leads to environmental pollution with heavy metals, and the crystallized water contained in sulfate molecules in the premixes destroys vitamins and other biologically active substances. The degree of assimilation of trace elements increases with the use of feed additives with trace elements of organic origin. Representatives of such feed additives are mixed ligand complexes of trace elements (chelates). Taking into account the fact that suckling piglets need Ferrum addition to mother's milk and a sufficient amount of Cuprum on the 4–5th day of life since Cuprum catalyzes the incorporation of Ferrum into the heme structure and is an indispensable activator of hemoglobin synthesis and a stimulator of erythrocyte maturation, the study of the action of this element in the composition of a mixed ligand of the complex in the pre-starter compound feed is relevant. In addition, the study of the economic and economic significance of the use of the mixed ligand complex of Cuprum in the feeding of suckling piglets, the establishment of optimal norms of this supplement taking into account the breed and parent age, has an important scientific and practical significance. The domestic and foreign experience of effective pig farming shows that the realization of the hereditary qualities of modern high-performance pig breeds and obtaining ecologically clean products is possible only under the condition of the development and implementation of perfect technologies for the production of pig farming products, which must be consistent with the biological needs of animals.

Clinical haematobiochemical parameters during experimental lead poisoning in goats: effects of methanol extract of Tiger nuts

The effects of methanol extract of tiger nut on haematobiochemical parameters during experimental lead poisoning in Red Sokoto goats were investigated. The seeds of tiger nuts were extracted with 90% methanol. Phytochemical analyses were carried out using standard procedures. A total of twenty-four adult Red Sokoto goats of both sexes were separated randomly into four groups for acute and chronic studies. Three goats in both acute and chronic studies were housed per group. In the acute and chronic studies DW groups was administered an equivalent amount of distilled water (400 and 200 ml/kg). Group II was only administered lead acetate (400 and 200 mg/kg). Group III was administered with methanol extract of tiger nuts (400 and 200 mg/kg) combined with lead acetate (400 and 200 mg/kg) respectively. Group IV was administered with tiger nuts (400 and 200 mg/kg) only for a period of 2 and then 20 weeks for acute and chronic phases respectively. Haematobiochemical parameters were determined. The lead acetate and lead acetate combined with methanol extract of tiger nut in acute and chronic groups showed microcytic normocytic and microcytic hypochromic anaemia respectively with the latter suggestive that with chronicity, an enzymatic inhibition of haemoglobin synthesis led to iron deficiency. Alterations in serum biochemical enzymes and other parameters indicative of hepato-renal injury were observed and ameliorated by methanol extract from tiger nuts

Progress of CRISPR/Cas9 in the treatment of sickle cell disease

Sickle cell disease (SCD) is a hereditary monogenic disease, which is characterized by the substitution of glutamic acid at the sixth position of β-peptide chain by valine, resulting in insufficient hemoglobin synthesis and a serious threats to human health. SCD causes about 80% of mortality and morbidity worldwide. Patients with SCD who are homozygous usually die before the age of 30. Patients with SCD who are heterozygous usually have a better prognosis because of their low intraerythrocytic hemoglobin S. However, FDA-approved drugs such as hydroxyurea and L-glutamine can reduce the severity of the disease, and there is no definite cure for all patients with SCD. At this stage, many scholars use creation and correction methods to induce pluripotent stem cells (IPSCs) to treat sickle cell disease. Gene editing is currently considered to be one of the most potential methods for the treatment of SCD. Among them CRISPR/Cas9 gene editing engineering technology has already made an abyss contribution to the transformation of genome engineering and its application in clinical or medical experiments. This review systematically introduces the gene therapy of CRISPR/Cas9, and summarizes the challenges and prospects of this technique in the treatment of sickle cell anemia.

Prevalence Rate of Thalassemia Carriers among Individuals with Microcytosis or Hypochromia in Portugal.

Microcytosis and hypochromia result from deficient hemoglobin synthesis in red blood cells and are easily detected in a complete blood count test. These conditions are mainly due to iron nutritional deficiency, but may also result from some genetic diseases, such as thalassemia. The aim of this study was to determine the contribution of β- and α-thalassemia to these abnormal hematological phenotypes in a representative sample of adult individuals living in Portugal who participated in the first Portuguese National Health Examination Survey (INSEF). Among the 4808 INSEF participants, 204 had microcytosis, hypochromia or both. The corresponding 204 DNAs were screened for changes in the β-globin gene by next-generation sequencing and Sanger sequencing. In addition, α-thalassemia deletions within the α-globin cluster were investigated by Gap-PCR and multiplex ligation-dependent probe amplification. In this selected subgroup of INSEF participants, 54 had α-thalassemia (26%), predominantly caused by the -α3.7kb deletion, and 22 were β-thalassemia carriers (11%) mainly due to point mutations in the β-globin gene previously known in Portugal. Thalassemia trait is a frequent cause of microcytosis or hypochromia in Portugal since this genetic condition was found in 37% of the investigated cases.

Clinical utility of targeted next-generation sequencing panel in routine diagnosis of hereditary hemolytic anemia: A national reference laboratory experience.

Hereditary hemolytic anemias (HHA) comprise a heterogeneous group of disorders resulting from defective red blood cell (RBC) cytoskeleton, RBC enzyme deficiencies, and hemoglobin (Hb) synthesis disorders such as thalassemia or sideroblastic anemia. Our hemolytic anemia diagnostic next-generation sequencing (NGS) panel includes 28 genes encoding RBC cytoskeletal proteins, membrane transporter, RBC enzymes, and certain bilirubin metabolism genes. The panel covers the complete coding region of these genes, splice junctions, and, wherever appropriate, deep intronic or regulatory regions are also included. Four hundred fifty-six patients with unexplained hemolytic anemia were evaluated using our NGS panel between 2015 and 2019. We identified pathogenic/likely pathogenic variants in 111/456 (24%) patients that were responsible for the disease phenotype (e.g., moderate to severe hemolytic anemia and hyperbilirubinemia). Approximately 40% of the mutations were novel. As expected, 45/456 (10%) patients were homozygous for the promoter polymorphism in the UGT1A1 gene, A(TA)7 TAA (UGT1A1*28). 8/45 homozygous UGT1A1*28 cases were associated with additional pathogenic mutations causing hemolytic anemia, likely exacerbating hyperbilirubinemia. The most common mutated genes were membrane cytoskeleton genes SPTA1, and SPTB, followed by PKLR. Complex interactions between SPTA1 low expression alleles, alpha-LELY and alpha-LEPRA alleles, and intragenic SPTA1 variants were associated with hereditary pyropoikilocytosis and autosomal recessive hereditary spherocytosis in 23/111 patients. Our results demonstrate that hemolytic anemia is underscored by complex molecular interactions of previously known and novel mutations in RBC cytoskeleton/enzyme genes, and therefore, NGS should be considered in all patients with clinically unexplained hemolytic anemia and in neonates with hyperbilirubinemia. Moreover, low expression alleles alpha-LELY and alpha-LEPRA should be included in all targeted HHA panels.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

HUBUNGAN TINGKAT KEPATUHAN KONSUMSI OBAT KELASI BESI DENGAN KADAR FERRITIN PADA PASIEN THALASSEMIA ANAK DI RSUD DR. MOEWARDI

Thalassemia is a hereditary hemolytic disease caused by mutations in the hemoglobin synthesis chain. Transfusion-dependent thalassemia patients require iron chelation therapy to prevent complications of iron overload. Adherence with regular iron chelation consumption is important for good survival, reducing morbidity and mortality in thalassemia patients. This research is an analysis of an observational study with a cross-sectional approach. This research was conducted at RSUD Dr. Moewardi. The subjects of this study were pediatric thalassemia patients who were taking deferiprone iron chelating drugs. The sample was taken using purposive sampling method, by analysing medical record data and the MMAS-8 questionnaire. Data were examined using the chi-square test with the SPSS application. Results: There were 56 subjects to be analyzed consisting of 23 males and 33 females. Based on the chi-square test, there was a significant relationship between consumption of iron chelating drugs and ferritin levels with p = 0.026. In addition, another study was conducted using the chi-square test regarding nutritional status and duration of thalassemia illness on ferritin levels. The results obtained were p value = 0.977 for the relationship between nutritional status and p value = 0.977 for the long duration of thalassemia illness. It can be concluded that both of them have no significant effect on ferritin levels. Adherence with taking iron chelating drugs has a significant relationship to ferritin levels in thalassemia patients.

СРАВНИТЕЛЬНЫЙ АНАЛИЗ СЕКРЕЦИИ ИНТЕРЛЕЙКИНА-6, ИНТЕРЛЕЙКИНА-1БЕТА, ИНТЕРЛЕЙКИНА-10, ФАКТОРА НЕКРОЗА ОПУХОЛИ-АЛЬФА, ИНТЕРФЕРОНА-ГАММА ПРИ РАЗЛИЧНЫХ ТИПАХ АНЕМИИ У ПАЦИЕНТОВ С ВИЧ-ИНФЕКЦИЕЙ

Aim. To compare the secretion of interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1-beta, tumor necrosis factor-alpha (TNF-α), interferon-gamma (INF-γ) in patients with HIV infection with anemia of chronic disease (ACD), iron deficiency anemia (IDA), as well as their combination. To assess the effect of the studied cytokines on erythropoiesis in each of the studied types of anemia in this category of patients. Material and methods. 125 patients with HIV infection were examined: 101 with anemia (55 men, 46 women, 39.4±9.6 years), 24 patients with HIV infection without anemia (13 men, 11 women, mean age 37.6± 7.37 years). In accordance with the Van Santen and Worwood criteria, by determining the transferrin saturation index (TSI), ferritin concentrations, C-reactive protein (CRP), patients with anemia were divided into 3 groups: group 1 – 36 patients with ACD (19 men, 17 women, mean age 41.7±11.8 years), group 2 – 30 patients with a combination of ACD/IDA (18 men, 12 women, mean age 41.2±10 years), group 3 – 35 patients with IDA (18 men, 17 women, mean age 35.4±7.1 years). In all patients, the number of erythrocytes, the concentration of hemoglobin, ferritin, CRP, CNT, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-1beta (IL-1β), interferon-gamma (INF-γ). For quantitative indicators, the arithmetic mean, standard error of the mean, and interquartile range (IQR) were calculated. Significance of differences between several unrelated groups was determined using the Kruskal-Wallis’s test. To assess the relationship between variables, the Spearman correlation coefficient I was calculated. Results. In the ACD group, the maximum concentration of IL-6 (36.6 [IQR, 11.5-51.1]) and IL-10 (21.6 [IQR, 11.4-28.8]) compared with the ACD/IDA group (IL-6 (9.1 [IQR, 5.1-11.4]), IL-10 (15.5 [IQR, (7.1-21.6)]), and IDA (IL- 6 (6.2 [IQR, 1.6–7.2]), IL-10 (8.6 [IQR, 3.9–9.3]) (p&lt;0.05). In the groups of patients with ACD and ACD/IDA, the maximum and almost equal concentrations of TNF-α (15.2 [IQR,6.1-24.1] in the ACD group and 17.3[IQR,7.9-17.3] in the ACD/IDA group), IL-1β (16.7[IQR,4.7-28.9] in the ACD group and 19.2 [IQR,3.9-28.8] in the ACD/IDA group), INF-γ ( 62.6[IQR,4.6-85.3] in the ACD group and 58.3[IQR,8.5-37.5] in the ACD/IDA group), which were statistically significantly higher than the concentrations of these cytokines in patients with IDA and the control group. There were no significant differences in the concentrations of TNF-α, IL-1β, IL-10 and IFN-γ between patients with IDA and the control group. Significant moderate and strong negative correlations were found in the groups of patients with ACD and ACD/IDA between all studied cytokines, erythrocytes and hemoglobin. In the IDA group, the correlation coefficients between cytokines, erythrocytes, and hemoglobin are low or absent. Conclusions. In patients with HIV infection, a wide prevalence of ACD has been shown, especially in patients with immunodeficiency and in the late stages of the disease. ACD, unlike IDA, has a complex multicomponent pathogenesis. This study shows the importance of pro-inflammatory and inflammatory cytokines in the development of ACD in HIV patients, including due to their negative effect on erythropoiesis and hemoglobin synthesis. A working version of the classification of ACD (with a predominant iron deficiency, with impaired regulatory mechanisms of erythropoiesis, with insufficient production of erythropoietin) has been proposed. It is necessary to further study the pathogenesis of ACD in this category of patients to improve treatment.