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AbstractHemoglobin Tacoma is known to potentially interfere HbA1c assays. The variant is common in Finland with prevalence of up to 2% regionally and cases are also reported in areas that have attracted Finnish immigrants, especially in Sweden and North America. Here, we investigated the effect of Hb Tacoma on seven HbA1c methods. 20 non-variant and 20 Hb Tacoma samples were measured with Tina-quant Gen. 3 (immunoassay, considered as reference) and the following point of care instruments: Afinion 2, HbA1c 501 (both utilizing boronate affinity), QuikRead go, cobas b 101, DCA Atellica, and Standard F (all immunoassays). Repeatability was also assessed by measuring both non-variant and Hb Tacoma samples five times each at two different levels. For non-variant samples, the mean relative bias with all methods was < ±4%, whereas for Hb Tacoma samples Standard F had 38% mean relative bias. In absolute bias, the difference was 17 mmol/mol on average and constant through the measured range. For other methods the mean relative bias for Hb Tacoma samples was < ±6%. The repeatability with all methods was similar for non-variant and Hb Tacoma samples and at highest 4.1% (mean CV% of two levels). The observed interference by Standard F is likely due to two-antibody assay design as Hb Tacoma has been shown to result in conformational change. This interference is clinically significant and highlight the need for better controlling and better understanding hemoglobin variants in HbA1c testing. [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease (SCD) is the most common hemoglobinopathy worldwide, characterized by vaso-occlusive crises and ischemia that affects patients on a multi-system level. Despite being a genetically simple disease due to a single base mutation, SCD poses many therapeutic challenges. Additionally, its impact on patients' life remains significant. This narrative review aims to provide a snapshot of recent highlights of the significant progress in SCD therapy, and the impact of SCD on patients' life, including the complications, morbidity, and mortality factors of the disease. Methodology: Google Scholar and PubMed were searched for "sickle cell disease". Only full-text English language original research articles were included in this review. In total, 600 articles were screened, 300 from each database, which were published from 2020 to 2024-06-01. A total of 139 studies were included in this review, after screening for inclusion. Conclusions: The increasing global incidence of sickle cell disease underscores the urgency for healthcare interventions to address the health challenges of an aging population living with this chronic condition. While treatment options for sickle cell disease have broadened, their availability is still limited. Among these options, stem cell transplant stands out as the definitive treatment, with ongoing efforts to enhance the donor pool. The disease significantly affects patients' quality of life and overall health, with emerging neurological and psychiatric issues. Additionally, the impact of sickle cell disease on reproductive health in both men and women presents a pressing need for further research to meet reproductive challenges. [ABSTRACT FROM AUTHOR]

Introduction: Renal medullary carcinoma (RMC) is a rare form of renal cell carcinoma (RCC) that is typically associated with a loss of function in SMARCB1 and diagnosis of sickle cell or other hemoglobinopathy. In rare cases, this disease can be seen in patients without hemoglobinopathy and is classified as “SMARCB1-deficient RMC without hemoglobinopathy” or referred to as “RCC unclassified with medullary phenotype” in some of the literature. Platinum-based cytotoxic chemotherapy is currently the recommended first-line treatment for this rare disease. Case Presentation: Here we report a 53-year-old male who was diagnosed with metastatic SMARCB1-deficient RMC without hemoglobinopathy after presenting with left flank and abdominal pain. After initiating first-line pembrolizumab and lenvatinib systemic therapy, imaging showed regression at 6 weeks. To date, this patient continues to show a near complete response to this treatment regimen. Conclusion: To our knowledge, this is the first documented case of SMARCB1-deficient RMC without hemoglobinopathy to receive this treatment regimen and show such a response. [ABSTRACT FROM AUTHOR]

Introduction: Thalassemia is a blood disturbance occurred down during families (genetic) in which the body produces an abnormal shape hemoglobin. This disorder results in excessive destruction at red blood cells, and there is not effective therapy. Patients require lifelong blood transfusion, usually started within 6 to 12 months of birth of the patient, which on other hand has its own many complications. It is a chronic disease that manifests so early in life that it leads to psychological and social problems for parents. Objectives, (1) to identify economic burdens that affects the families of thalassemia Children in general Center for the treatment of Thalassemia at Misan City.(2)to Examine relationships between economic burdens that affects the families of Thalassemia and their perceived socio-demographic related data. Methodology: In this study was used convenient sampling; 53 Children collected representing to the parents of children thalassemia. a questionnaire is constructed by the researchers for the purpose of the study. It is comprised of two parts: First part of questionnaire: Demographic data. consisted of (12) items, Second part of questionnaire: specific information to sample research. That contains of (26) items. The data collected during period from 10 November 2020 and ended in 20 May 2021. Results, The results of study show that more of the children in age group to the study sample were within (6-10) years was (30.2%).The study also shows that the majority of participants were male (62.3%). that there was high significant relationship between the effect of economic burden toward parents children of thalassemia and their economic status at (P > 0.05).in regarding to the subjects number of family members, the results show that more half of them in age group to the study sample were within (6-10) years was (69.8%). Conclusion, The findings there was high significant relationship between the effect of economic burden toward parents children of thalassemia and their economic status. the results show that more half of them in age group to the study sample were within (6-10) years was, The findings also revealed The majority of the samples suffer from a low economic level. Recommendation, The disease is among the hereditary diseases that are transmitted from parents who carry the disease to their children. Therefore, we recommend blood tests before marriage to avoid infecting children and what complications happen to them that lead to their death. The necessity of early diagnosis of the disease for the purpose of using appropriate treatment methods to avoid serious complications in the future, such as removing some organs such as the liver, spleen or even the bone marrow. [ABSTRACT FROM AUTHOR]

Background: Isotretinoin is an effective treatment for acne but can cause side effects such as changes in blood lipids and liver enzymes. Laboratory monitoring is essential during treatment, but there is variation in monitoring practices. Aim: This study aims to investigate the relationship between isotretinoin therapy and its effects on complete blood count in Saudi Arabia to improve patient outcomes. Methods: The study was a retrospective cohort study conducted at King Khalid University Hospital in Riyadh, Saudi Arabia, between January 2016 and December 2020. Following the inclusion and exclusion criteria, 515 patients were randomly selected for the study. The data was analyzed using SPSS, and descriptive statistics and paired samples t-tests were employed to analyze the data. Results: In this study, 515 patients were enrolled. Of these participants, 76.7% (n=395) were females and 23.3% (n=120) were males. The mean age of the study participants was 23.98± 7.4 years and ranged between 16 and 65 years. The mean dose of Isotretinoin administered was 27.65± 9.6 mg/day, with a range of 10– 60 mg/day. The mean BMI of the study participants was 24.3± 4.1 kg/m2, ranging from 14.3 to 44.8 kg/m2. Regarding the effect of Isotretinoin on laboratory measures, significant statistical differences were found in hemoglobin measurements (t=− 3.379, p=0.001), platelets (t=− 3.169, p=0.002), neutrophils (%) (t=3.107, p=0.002), total cholesterol (t=− 13.017, p=0.000), AST (t=− 6.353, p=0.000), ALT (t=− 4.352, p=0.000), HDL (t=2.446, p=0.015), and LDL (t=− 12.943, p=0.000). However, there were no significant statistical differences in the measurements of WBC, neutrophils (count), or triglycerides. In the Chi-square analysis and Fisher's Exact test to identify the interaction between BMI, dose, and gender on abnormal lab results, significant interaction was found between participants' BMI and abnormal HDL measurements (p=0.006). Furthermore, there were significant interactions between Isotretinoin dose (either less than 30 mg/day or 30 mg/day or more) and abnormal neutrophil count (p=0.04), abnormal HDL measurements (p=0.010), and abnormal triglycerides measurements (p=0.020). Moreover, a statistically significant interaction was found between participants' gender and abnormal hemoglobin measurements (p=0.006), abnormal total cholesterol (p=0.016), abnormal AST measurements (p=0.001), abnormal ALT measurements (p=0.000), abnormal HDL measurements (p=0.000), and abnormal triglycerides measurements (p=0.007). Conclusion: In conclusion, the study found that isotretinoin therapy has significant effects on several laboratory measures, including hemoglobin, platelets, neutrophils, total cholesterol, AST, ALT, HDL, and LDL. The study also revealed significant interactions between BMI, dose, gender, and abnormal lab results. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) is a hereditary blood disorder characterized by abnormal hemoglobin, leading to the sickle shape of red blood cells. It has several vascular complications and the cerebrovascular ones are among the most frequent and severe both in children and in adults. This review summarizes the main neurovascular manifestations of SCD, including acute stroke, silent cerebral infarction, large-vessel diseases (moyamoya arteriopathy and aneurysms), and brain bleeding. Both epidemiology, pathophysiology, and treatment issues are addressed and prevention of cerebrovascular events, including silent cerebral infarctions, is particularly relevant in SCD patients, being associated to poor functional outcome and cognitive complaints. Transfusions and hydroxyurea are the main available therapy at the moment, but contraindications, availability, and complications might prevent their long term use, particularly in low-income countries. The role of transcranial Doppler in monitoring the patients (mainly children) is analyzed and a practical approach has been selected in order to give the main messages from the current literature for a better management of SCD patients. [ABSTRACT FROM AUTHOR]

Reproductive genetic carrier screening (RGCS) serves to screen couples for their risk of having children affected by monogenic conditions. The included conditions are mostly autosomal recessive or X-linked with infantile or early-childhood onset. Cystic fibrosis, spinal muscular atrophy, and hemoglobinopathies are now recommended by the American College of Obstetricians and Gynecologists (ACOG) for universal screening. Recommendations for further RGCS remain ethnicity based. The American College of Medical Genetics and Genomics and the National Society of Genetic Counselors in recent years have recommended universal expanded-panel RGCS and moving towards a more equitable approach. ACOG guidelines state that offering RGCS is an acceptable option, however it has not provided clear guidance on standard of care. Positive results on RGCS can significantly impact reproductive plans for couples, including pursuing in vitro fertilization with preimplantation genetic testing, prenatal genetic testing, specific fetal or neonatal treatment, or adoption. RGCS is a superior approach compared to ethnicity-based carrier screening and moves away from single race-based medical practice. We urge the obstetrics and gynecology societies to adopt the guidelines for RGCS put forward by multiple societies and help reduce systemic inequalities in medicine in our new genetic age. Having national societies such as ACOG and the Society for Maternal-Fetal Medicine officially recommend and endorse RGCS would bolster insurance coverage and financial support by employers for RGCS. The future of comprehensive reproductive care in the age of genomic medicine entails expanding access so patients and families can make the reproductive options that best fit their needs. [ABSTRACT FROM AUTHOR]

Introduction: Sickle cell disease is an inherited disorder characterized by hemoglobin S polymerization leading to vaso-occlusion and hemolytic anemia. These result in a variety of pathological events, causing both acute and chronic complications. Millions around the world are affected by sickle cell disease with predominance in sub-Saharan Africa. Hydroxyurea was the first drug approved for use in sickle cell disease to reduce the occurrence of painful crises and blood transfusions in patients with frequent, moderate to severe painful crises. Areas covered: With the development of new therapeutics, the role of hydroxyurea is evolving. This narrative review aims to provide clinical data, safety information, and supplementary evidence for the role of hydroxyurea in the current era of sickle cell disease. A comprehensive literature search of databases, including PubMed and Cochrane Library, was conducted from 1963 to 2024. Expert opinion: Even though new medications have been approved for sickle cell disease, hydroxyurea remains the gold standard. Hydroxyurea is not only a disease modifier but it has additional clinical benefits, it is affordable, and its longevity has prompted expanded research in areas such as underutilization and pharmacogenomics. As the treatment landscape evolves, hydroxyurea's long-standing record of efficacy and safety continues to support its role as a key agent in disease management. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to evaluate prothrombin time/international normalized ratio (PT) along with activated partial thromboplastin time (APTT) and its association with platelet and red blood cell (RBC) cell population data for initial assessment of thrombotic tendencies. Materials and Methods: Blood samples of 43 patients diagnosed with a beta-thalassemia major who were transfusion dependant were taken for assessment of mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) along with RBC distribution width and correlated with APTT. Results: Elevated APTT and PT were noted among patients with thalassemia along with elevated PCT and red cell distribution width-coefficient of variation (RDW-CV). Reduced PDW was noted. Elevated APTT was positively associated with RDW and MPV and negatively associated with PDW and PCT. Conclusion: In our study, elevated levels of PCT RDW CV, PT, and APTT were observed. Elevated levels of APTT were also noted to be positively correlated with MPV and RDW CV.

Abstract Background Sickle cell disease (SCD) is the most common hemoglobinopathy worldwide, characterized by vaso-occlusive crises and ischemia that affects patients on a multi-system level. Despite being a genetically simple disease due to a single base mutation, SCD poses many therapeutic challenges. Additionally, its impact on patients’ life remains significant. This narrative review aims to provide a snapshot of recent highlights of the significant progress in SCD therapy, and the impact of SCD on patients’ life, including the complications, morbidity, and mortality factors of the disease. Methodology Google Scholar and PubMed were searched for “sickle cell disease”. Only full-text English language original research articles were included in this review. In total, 600 articles were screened, 300 from each database, which were published from 2020 to 2024-06-01. A total of 139 studies were included in this review, after screening for inclusion. Conclusions The increasing global incidence of sickle cell disease underscores the urgency for healthcare interventions to address the health challenges of an aging population living with this chronic condition. While treatment options for sickle cell disease have broadened, their availability is still limited. Among these options, stem cell transplant stands out as the definitive treatment, with ongoing efforts to enhance the donor pool. The disease significantly affects patients' quality of life and overall health, with emerging neurological and psychiatric issues. Additionally, the impact of sickle cell disease on reproductive health in both men and women presents a pressing need for further research to meet reproductive challenges.

Human pythiosis is a rarely encountered yet potentially harmful infectious disease. It is mostly caused by Pythium insidiosum, an aquatic fungal‐like organism, and primarily manifests in tropical locales such as India and Thailand. Cutaneous/subcutaneous pythiosis accounts for a small proportion of all clinical forms. The relationship between cutaneous pythiosis and hemoglobinopathy remains uncertain, unlike the vascular form. The histopathology of the disease demonstrates eosinophilic granulomatous inflammation and dense eosinophilic material enveloping the organism, known as the Splendore–Hoeppli phenomenon. These histopathologic characteristics resemble those observed in entomophthoromycosis. Until now, the histopathology of human cutaneous pythiosis has been scarcely delineated in the literature. Herein, we report a case of cutaneous pythiosis in an adult thalassemic agricultural worker who presented with a 2‐month history of a progressive, painful, erythematous infiltrative plaque on the left leg. The definitive diagnosis was ascertained through histopathologic examination and the identification of anti‐P. insidiosum antibodies in the serum utilizing enzyme‐linked immunosorbent assay. This report demonstrates the exquisite histopathologic findings of a rare case of human cutaneous pythiosis. [ABSTRACT FROM AUTHOR]

Emmanuel Ifeanyi Obeagu,1 Getrude Uzoma Obeagu2 1Department of Medical Laboratory Science, Kampala International University, Ishaka, Uganda; 2School of Nursing Science, Kampala International University, Ishaka, UgandaCorrespondence: Emmanuel Ifeanyi Obeagu, Department of Medical Laboratory Science, Kampala International University, Uganda, Email emmanuelobeagu@yahoo.comAbstract: Sickle Cell Anemia (SCA) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin, leading to the formation of sickle-shaped red blood cells. While extensive research has unraveled many aspects of the genetic and molecular basis of SCA, the role of telomere dynamics in disease progression remains a relatively unexplored frontier. This review seeks to provide a comprehensive examination of telomere biology within the context of SCA, aiming to elucidate its potential impact on molecular aging and the progression of the disease. The impact of oxidative stress on telomere dynamics in SCA is explored, with a particular focus on how increased reactive oxygen species (ROS) may contribute to accelerated telomere shortening and genomic instability. Furthermore, the potential relationship between telomere dysfunction and cellular senescence in SCA is investigated, shedding light on how telomere dynamics may contribute to the premature aging of cells in this population. The review concludes by summarizing key findings and proposing potential therapeutic strategies targeting telomere dynamics to mitigate disease progression in SCA. It also identifies gaps in current understanding and suggests avenues for future research, emphasizing the importance of further investigating telomere biology to advance our understanding of molecular aging and disease progression in Sickle Cell Anemia. This comprehensive exploration of telomere dynamics in SCA offers insights into potential mechanisms of molecular aging and disease progression, paving the way for targeted therapeutic interventions and improved disease management.Keywords: sickle cell anemia, telomere, molecular aging, hemoglobinopathy, telomere shortening, oxidative stress

In medical diagnostics, variations in hemoglobin levels can reveal a variety of prevalent health conditions. Abnormal hemoglobin is known to be connected with diseases like anemia, diabetes, hematemesis, hematuria, and hemoglobinuria. Consequently, there is a significant demand for advanced detection technologies and precise methodologies to accurately track and assess hemoglobin levels. This study demonstrates the potential of a novel molecularly imprinted nanoparticle‐based sensor system to rapidly analyze hemoglobin levels without the need for a laboratory environment. Hemoglobin imprinted‐poly(acrylamide‐co‐vinyl imidazole) [Hb‐imp‐p(AAm‐co‐VIM)] nanoparticles with high affinity and selectivity for hemoglobin were synthesized and loaded onto the surface of a screen‐printed carbon electrode (SPCE) with a nafion nanofilm. Nafion has selective ion exchange properties and allows for the enhancement of the electrochemical signal. An increase in signal was observed in the presence of 0.5% Nafion. The Hb‐imp‐p(AAm‐co‐VIM)/Nafion‐SPCE system was employed as the sensor surface for the detection of hemoglobin levels in blood. The Hb‐imp‐p(AAm‐co‐VIM)/Nafion‐SPCE system was characterized by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) measurements. The linear working range for hemoglobin was observed to be 0.73–15.54 μM (R2: 0.9934), with a calculated limit of detection (LoD) value of 0.24 μM (3.3 S/N). The sensor system exhibited high efficiency at the biological pH value of 7.4. Furthermore, percent recovery values for hemoglobin in blood samples were observed to be between 90.34% and 103.68%. To determine the selectivity of the Hb‐imp‐p(AAm‐co‐VIM)/Nafion‐SPCE electrode system, the current values of the system were investigated in the presence of ascorbic acid, cysteine, glucose, and IgG. The system exhibited high selectivity. Based on the data obtained, it is evident that the Hb‐imp‐p(AAm‐co‐VIM)/Nafion‐SPCE system can detect hemoglobin in biological environments and has the potential for use in disease monitoring systems. [ABSTRACT FROM AUTHOR]

Hemoglobin Shaare Zedek (Hb SZ) is a rare structural α-Hb variant. Characterizing its genotype–phenotype relationship and genetic origin enhances diagnostic and clinical management insights. We studied a proband and six family members using high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), PCR, and sequencing to analyze α- and β-globin genes and α-globin haplotypes. Pathogenicity predictions and a rapid diagnostic method were developed. The proband, his father, grandfather, and aunt had Hb migrating to the HbH-zone on CE and elevated fetal hemoglobin (HbF) on HPLC. Direct sequencing identified an A to G mutation at codon 56 of the α2-globin gene, characteristic of Hb SZ. Additionally, the proband carried a β-globin gene mutation [HBB.52A>T]. Mild thalassemia-like changes were observed in the proband, whereas individuals with only the Hb SZ variant did not exhibit these changes. Pathogenicity predictions indicated that Hb SZ is benign. The variant can be identified using restriction fragment length polymorphism (RFLP) and allele-specific PCR. The Thai variant of Hb SZ is associated with the haplotype [- - M - - - -]. Hb SZ is a non-pathological variant that minimally affects red blood cell parameters, even when it coexists with β0-thalassemia. HPLC and CE systems cannot distinguish it from other Hbs, necessitating DNA analysis for accurate diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the synergistic interaction effect between hyperuricemia and hypertension towards chronic kidney disease in patients with type 2 diabetes. Methods: This research originates from a cross-sectional study performed in Zhejiang Province, Eastern China, between March and November 2018. The correlation between serum uric acid levels and the risk of chronic kidney disease was assessed using a restricted cubic spline model. An unconditional multivariable logistic regression model, along with an interaction table, was utilized to explore the potential interaction effect of hyperuricemia and hypertension towards chronic kidney disease. Results: 1,756 patients with type 2 diabetes were included in this study, the prevalence of chronic kidney disease (CKD) was 27.62% in this population. A Ushaped non-linear pattern emerged correlating serum uric acid (SUA) levels and CKD risk, indicating that both low and high SUA levels were linked to an increased CKD risk. This risk achieved its lowest point (nadir) at SUA approximately equals to 285mmol/L (p for trend <0.05). Once adjustments for age, gender, education level, abnormal fasting plasma glucose (FPG), abnormal hemoglobin A1c (HbA1c), abnormal total cholesterol (TC), abnormal high-density lipoprotein cholesterol (HDL-C), alcohol consumption and duration of diabetes were factored in, it was found that patients with both hyperuricemia and hypertension demonstrated a 5.42-fold (95% CI: 3.72--7.90) increased CKD risk compared to the reference group. The additive interaction between hyperuricemia and hypertension was statistically significant, as manifested by the following values: a relative excess risk due to interaction (RERI) of 2.57 (95% CI: 0.71--4.71), an attributable proportion due to interaction (AP) of 0.47 (95% CI: 0.14--0.64), and a synergy index (SI) of 2.39 (95% CI: 1.24--4.58). In contrast, there was no significant interaction effect in multiplicative scale. Conclusion: Hyperuricemia and hypertension may contribute additively to CKD, beyond their isolated impacts. Evaluating the risk of CKD in type 2 diabetes patients necessitates considering this potential interaction. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of clinico-hematological features and JAK 2 status of young adults presenting with Polycythemia Vera at the department of hematology. Study Design: Cross-sectional study. Setting: Department of Hematology, RMI Hospital, Peshawar. Period: 25th November 2023 to 25th May 2024. Methods: A total of 190 patients aging between 18-45 years and presented as suffering from Polycythemia Vera as per diagnosis of consultant hematopathologists, were included in this study. Samples with clear evidence of hemolysis, coagulation, or clots were excluded. Patient's demographics, details of physical appearance, clinical findings and history of adverse events were recorded. Hematological and pathological investigations were done and analysis of JAK2 V617F mutation was conducted using polymerase chain reaction from the diagnostic lab of the institute. The primary outcome of the study was to determine the frequency of clinicohematological features and JAK 2 status. Results: The Mean±SD of age in our study was 36.81±6.11 years with an age range of 21-45 years. Out of total patients, 49 (25.79%) patients were asymptomatic. The major symptoms affecting the daily life activities were headache 65 (34.21), abdominal discomfort 41 (21.58%), blurred vision 27 (14.21%) and fatigue 27 (14.21%). These patients had plethoric face 61 (32.11%), splenomegaly 64 (33.68%) and budd-chiari syndrome 8 (4.21%). The results of hematopathological findings showed abnormal hemoglobin (17±3.92 gm/dL), hematocrit (52.94±4.8 g %), platelet (579.63±227.68 103/μL) and leukocyte (10.32±2.6, 10³/μL) levels while 177 (93.16 %) patients had mutated JAK2 levels. Conclusion: Plethoric face and splenomegaly are the commonly found clinical findings in patients with Polycythemia Vera while these patients also have abnormal levels of hemoglobin, hematocrit, platelet and leukocyte. JAK 2 status serves conclusive role in the diagnosis of Polycythemia Vera. [ABSTRACT FROM AUTHOR]

Sickle Cell Anemia (SCA), is an inherited hemoglobinopathy characterized by the presence of an abnormal hemoglobin (HbS), being the most prevalent sickle cell disease (SCD). SCA is characterized by vascular endothelial dysfunction, which contributes significantly to various clinical conditions, including but not limited to pulmonary hypertension, priapism, cutaneous leg ulceration, and stroke. The pathophysiology of endothelial dysfunction (ED) in SCA is a multifaceted process involving a chronic inflammatory and hypercoagulable state. Key factors include hemolysis-associated elements like reduced arginine and nitric oxide (NO) availability, elevated levels of vascular adhesion molecules, the uncoupling effect of NO synthase, heightened arginase activity, an environment characterized by oxidative stress with the production of reactive oxygen and nitrogen species, and occurrences of ischemia-reperfusion injury, along with apolipoprotein A-1 depletion. The urgency for novel interventions addressing ED is evident. Presently, there is a focus on investigating small molecules that disrupt the arginine-nitric oxide pathway, exhibiting anti-inflammatory and antioxidant properties while diminishing levels of cellular and vascular adhesion molecules. In this mini-review article, we delve into the progress made in strategies for treating ED in SCD with the aim of cultivating insights for drug design. [Display omitted] • ED is a vasculopathy found in SCD patients responsible for pulmonary arterial hypertension, priapism, and leg ulcers. • Low NO bioavailability, activated endothelial cells, and high levels of ROS are the main characteristics in ED. • NO-donors, sGC stimulators and activators, antioxidants, supplementation of vitamins and arginine are the focus of this review. • FDA approved drugs such as HU and l-glutamine also play an important role in ED, ameliorating the oxidant profile. [ABSTRACT FROM AUTHOR]

Little is known about diabetes risk in adolescents and young adults with Fontan palliation. We sought to understand the prevalence of abnormal hemoglobin A1c (HbA1c) in the adolescent and young adult population with Fontan palliation. Between 2015 and 2021, 78 Fontan patients > 10 years of age were seen in our single ventricle clinic; 66 underwent screening with HbA1c. 50% of the study cohort (n = 33) had HbA1c ≥ 5.7%; 2% (n = 1) had HbA1c ≥ 6.5%. There was no correlation between BMI and HbA1c, with no difference in the prevalence of overweight or obesity (BMI ≥ 85th percentile) between those with and without abnormal HbA1c (31% versus 27%, p = 0.69). While 20% of the cohort had a family history of diabetes, there was no difference in family history between those with and without abnormal HbA1c (21% versus 19%, p = 0.85). There were no differences in other risk factors and characteristics (race, glomerular filtration rate, liver function, liver elastography, hematocrit, and years from Fontan surgery) between those with and without abnormal HbA1c. Our results highlight the importance of recognizing that abnormal HbA1c is highly prevalent in the Fontan population. Whether abnormal HbA1c in this population correlates with atherosclerotic cardiovascular disease in adulthood is not known. The mechanism for an abnormal HbA1c in the adolescent and young adult Fontan population remains unclear and further studies are needed. [ABSTRACT FROM AUTHOR]

The process of screening aims to reduce the burden of disease. In pregnancy this is relevant to both the mother and her baby. There are national screening programmes for infectious disease, haemoglobinopathy and fetal anomalies, all of which have the potential to reduce the life-long burden of disease in the newborn. But screening extends beyond these programmes and when risk factors are identified, interventions might be instigated to reduce the impact of disease on pregnancy outcomes. This article reviews screening in its broadest sense. It describes the various screening opportunities and considers the actions that can be taken to optimize the health of the mother and her baby. The process of screening continues throughout pregnancy, in the same way that risks evolve as pregnancy progresses. [ABSTRACT FROM AUTHOR]

Hemoglobin (Hb) H disease presents a wide range of clinical phenotypes, from asymptomatic to severe forms, depending on significant genetic heterogeneity. This is the first report of clinical and hematological features of the nondeletional HbH disease caused by --CR/αCSα. A baby was born to a father and a mother with --CR and αCSα carriers, respectively. She had severe symptomatic hypochromic microcytic anemia at 2 months of age with Hb 7.8 g/dL, packed cell volume (PCV) 0.27 L/L, mean corpuscular volume (MCV) 64.3 fL, and mean corpuscular Hb (MCH) 18.3 pg. The Hb analysis using capillary electrophoresis (CE) showed Hb Bart's, HbH, and Hb CS peaks at 17.1%, 2.2%, and 1.6%, respectively. A better understanding of a patient's clinical and hematological features with --CR/αCSα is useful for hemoglobinopathy counseling for the national thalassemia controlling program. [ABSTRACT FROM AUTHOR]

We report the discovery of a novel β-globin gene variant, Hb Odder, characterized by a single nucleotide substitution; HBB:c.316C > G; CD105 (Leu > Val). This variant emerged incidentally during routine HbA1c measurements for diabetes monitoring. The patient exhibited no clinical or biochemical evidence of anemia or hemolysis. Our data on this variant suggest that Hb Odder is benign, regrettably limitations in our data make formal evaluations of stability and oxygen affinity impossible; additionally this emphasizes the importance of considering hemoglobin variants in the differential diagnosis of abnormal Hb A1c levels and suggest that laboratories should use alternative methods for the correct measurement of Hb A1c when hemoglobin variants interfere with diabetes monitoring. Notably, three other mutations have been described at codon 105 of the β globin chains and correspond to three Hb variants with different characteristics: Hb South Milwaukee, Hb Bellevue IV and Hb St. George. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) comprises inherited red blood cell disorders due to a mutation in the β-globin gene (c20A > T, pGlu6Val) and is characterized by the presence of abnormal hemoglobin, hemoglobin S, hemolysis, and vaso-occlusion. This mutation, either in a homozygous configuration or in compound states with other β-globin mutations, leads to polymerization of hemoglobin S in deoxygenated conditions, causing modifications in red blood cell shape, particularly sickling. Vaso-occlusive crisis (VOC) is the hallmark of the disease, but other severe complications may arise from repeated bouts of VOCs. SCD is considered a global health problem, and its incidence has increased in some areas of the world, particularly the Americas and Africa. Management of the disease varies according to the region of the world, mainly due to local resources and socioeconomic status. This review aimed to describe more recent data on SCD regarding available treatment options, especially in Brazil. New treatment options are expected to be available to all patients, particularly crizanlizumab, which is already approved in the country. [ABSTRACT FROM AUTHOR]

Hemoglobin diseases like sickle cell disease (SCD) and β-thalassemia (BT) present fertility challenges for affected patients. SCD and BT result from abnormal hemoglobin production or structure and pose numerous health concerns. Despite medical advancements improving the quality of life or even providing cures, SCD and BT pose unique fertility concerns for women. Young women with these disorders already contend with reduced ovarian reserve and a narrower fertile window, a situation that is compounded by the gonadotoxic effects of treatments like medications, transfusions, stem cell transplants, and gene therapy. While crucial for disease control, these interventions may lead to reproductive health issues, increasing infertility and early menopause risks. Ovarian tissue cryopreservation (OTC) offers potential for future motherhood to women with hemoglobin disorders facing infertility related to curative treatments. OTC involves surgically removing, preparing, and freezing ovarian tissue containing primordial follicles capable of producing mature oocytes, offering advantages over oocyte cryopreservation alone. However, the application of OTC for patients with hemoglobin disorders presents unique challenges, including special health risks, financial barriers, and access to care. This comprehensive literature review delves into the current state of ovarian tissue cryopreservation for fertility preservation in patients with hemoglobin disorders. Empowering patients with informed reproductive choices in the context of their hemoglobin disorders stands as the ultimate goal. [ABSTRACT FROM AUTHOR]

Background: Thalassemia is a genetic blood disorder in children that results in the production of abnormal hemoglobin, leading to severe anemia and the need for frequent blood transfusions. Without proper management, these transfusions can cause iron overload in the body, which can damage vital organs such as the heart and liver. Therapy with oral iron chelators is crucial for these children, as it helps to remove the excess iron and prevent potential complications. The aim of this study was to assess and compare the effectiveness and safety of oral iron chelators, both when administered alone and in combination, in children with thalassemia who receive several blood transfusions. Materials and Methods: The study was carried out in the Department of Pediatrics, Sri Balaji Medical College and Hospital, over a period of ¬¬¬¬24 months. The study included 75 children with thalassemia who had undergone several transfusions and were receiving daily treatment with iron chelation. Results: The current study included 75 children with thalassemia who had received multiple blood transfusions. For duration of 12 months, they received daily iron chelation therapy with either deferiprone alone (Group 1), deferasirox alone (Group 2), or a combination of the two (Group 3). The serum ferritin levels were found to be reduced in all 3 groups, however the difference was not significant. The hepatic T2- MRI values had increased from baseline to folloup, however the difference was significant only in Group 3. The reduction of cardiac T2* MRI value was significantly reduced in Group 3 from baseline to follow-up. Conclusion: This study concluded that deferiprone and deferasirox were effective and safe when administered alone in children with thalassemia who had received several transfusions. [ABSTRACT FROM AUTHOR]

Background and aim: Hemoglobinopathies pose to be a major risk factor for pregnancy leading to potentially fatal maternal and neonatal complications. The aim of our study was to compare maternal and neonatal outcomes of pregnancy in women with a hemoglobinopathy and without a hemoglobinopathy. Materials and methods: The present study is a comparative retrospective analysis of 153 pregnant women with hemoglobinopathies and 153 pregnant women without hemoglobinopathies who were treated between June 2020 and May 2023, in Dhiraj Hospital,Vadodara. We analyzed various data regarding maternal as well as neonatal outcomes and complications in hemoglobinopathies. Results: Among the maternal outcomes, the rate of previous miscarriage, intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and anemia were significantly increased in women with hemoglobinopathies. Among the neonatal outcomes, the rate of anemia and low birth weight were significantly increased in all type of hemoglobinopathic pregnancies. Hepatic encephalopathy, septicemia, jaundice, perinatal death, and fetal acidosis were also increased in sickle cell disease (SCD) pregnancies. Conclusion: It is pivotal to supervise pregnancies with hemoglobinopathies for minimal morbidity and mortality in mother as well as fetus. Timely multispecialty intervention can help in improving the fetomaternal outcomes. [ABSTRACT FROM AUTHOR]

Background: Hemoglobinopathy is considered a common monogenetic genetic disorder worldwide. Splenectomy is considered a therapeutic strategy in patients with hemoglobinopathy. The aim of current study was to provide a survey on the splenectomy and 5 years follow-up in different clinical forms of β-thalassemia (intermedia, Major) and Sickle cell Anemia (SCA) patients who referred to Hereditary Blood Disease Center in the Karbala Teaching Hospital for Children in Karbala, Iraq. Materials and Methods: In this retrospective study we tried to evaluate 126 hemoglobinopathy and thalassemia patients from Karbala City, Iraq. All cases of splenectomy due to hemoglobinopathy and thalassemia during 2010-2023 who referred to the Hereditary Blood Disease Center in the Karbala Teaching Hospital for Children in Karbala, Iraq were included. Patient data was collected at three-time points. The first was after the splenectomy, the second during 1-5 years, and the third step after 5 years. Clinical and laboratory data were retrieved from the patient's file. Results: The mean age of splenectomy of included patients was 14.1±7.5 years. From 126 cases, 103 (81.74%) were β-Thalassemia, 13 (10.32%) were SCA, and 10 (7.94%) were Sickle cell beta-thalassemia. The mean age in SCA was significantly less than two other groups (mean age in β-Thalassemia, SCA and Sickle cell beta thalassemia were 18.2±8.7, 24.2±12.7 and 25.2±9.5, respectively) (p=0.008). Platelet and WBC count represents a significant increase during 1-5 years after splenectomy in comparison with 1 year after splenectomy (for Platelet and WBC p=0.03 and 0.001, respectively). Conclusion: splenectomy is considered the last therapeutic option in hemoglobinopathy patients. All Hemoglobinopathy patients represented significant improvement after splenectomy. Because there was no suitable treatment in the past, splenectomy was considered a therapeutic solution. It should be said that periodic follow-up of splenectomy patients in hemoglobinopathy plays an important role in improving the management of these diseases. [ABSTRACT FROM AUTHOR]

Introduction: The NPRL3 gene is a critical component of the GATOR1 complex, which negatively regulates the mTORC1 pathway, essential for neurogenesis and brain development. Located on chromosome 16p13.3, NPRL3 is situated near the α-globin gene cluster. Haploinsufficiency of NPRL3, either by deletion or a pathogenic variant, is associated with a variable phenotype of focal epilepsy, with or without malformations of cortical development, with known decreased penetrance. Case Description: This work details the diagnostic odyssey of a neurotypical 10-year-old boy who presented at age 2 with unusual nocturnal episodes and a history of microcytic anemia, as well as a review of the existing literature on NPRL3-related epilepsy, with an emphasis on individuals with deletions who also present with α-thalassemia trait. The proband's episodes were mistaken for gastroesophageal reflux disease for several years. He had molecular testing for his α-thalassemia trait and was noted to carry a deletion encompassing the regulatory region of the α-thalassemia gene cluster. Following the onset of overt focal motor seizures, genetic testing revealed a heterozygous loss of NPRL3, within a 106 kb microdeletion on chromosome 16p13.3, inherited from his mother. This deletion encompassed the entire NPRL3 gene, which overlaps the regulatory region of the α-globin gene cluster, giving him the dual diagnosis of NPRL3-related epilepsy and α-thalassemia trait. Brain imaging postprocessing showed left hippocampal sclerosis and mid-posterior para-hippocampal focal cortical dysplasia, leading to the consideration of epilepsy surgery. Conclusions: This case underscores the necessity of early and comprehensive genetic assessments in children with epilepsy accompanied by systemic features, even in the absence of a family history of epilepsy or a developmental delay. Recognizing phenotypic overlaps is crucial to avoid diagnostic delays. Our findings also highlight the impact of disruptions in regulatory regions in genetic disorders: any individual with full gene deletion of NPRL3 would have, at a minimum, α-thalassemia trait, due to the presence of the major regulatory element of α-globin genes overlapping the gene's introns. [ABSTRACT FROM AUTHOR]

Introduction: Despite over 100 years of neglect and insufficient funding, sickle cell disease has risen to the top of the discussions due to the recent approval of two new genetic therapies. Prior to these approvals, there were only four prior approved medications for sickle cell disease in spite of being the most common inherited blood disorder. The advent and expense of these new genetic therapies have finally brought the trials and tribulations associated with SCD including the suffering and early mortality of affected individuals to the much-needed limelight. Presently, questions about how these therapies will be used and what that means for ongoing pharmaceutical development remain. Areas covered: Here, we wish to highlight the current medications and treatments for SCD using already published literature as well as scrutinize the tedious process of implementation for these newly approved commercial genetic therapies. Expert opinion: In our expert opinion, despite the progress we have made, significant challenges remain and the most important requirement for any of these treatments is ensuring all affected individuals have access to a sickle cell specialist who can provide comprehensive care. [ABSTRACT FROM AUTHOR]

Background: Glycated hemoglobin is a well-known marker for evaluating long-term glycemic control. However, the accuracy of glycated hemoglobin measurement can be affected by the presence of hemoglobin variants, which makes the determination and interpretation of glycated hemoglobin values in terms of glycemic control not only difficult but also misleading. Here we present the first ever case of a patient with type 2 diabetes with hemoglobin E from Nepal, diagnosed incidentally because of spurious glycated hemoglobin levels. Case presentation: A 45-year-old Hindu Mongolian female with a history of type 2 diabetes for around 9 years but not very compliant with follow-ups was referred to our facility for plasma fasting and postprandial blood glucose levels and glycated hemoglobin. Fasting and postprandial blood sugars were found to be high. A consistent very low glycated hemoglobin by two different high-performance liquid chromatography (HPLC) methods compelled us to call the patient for a detailed clinical history and for the records of investigations done in the past. The patient has been a known case of type 2 diabetes for around 9 years and presented irregularly for follow-up visits. Around 4 years ago, she presented to a healthcare facility with fatigue, severe headaches, pain in the abdomen, discomfort, and dizziness for a couple of months, where she was shown to have high blood glucose. She was referred to a tertiary-level hospital in Kathmandu, where she was prescribed metformin 500 mg once daily (OD). Due to her abnormal hemoglobin A1c reports, she was then sent to the National Public Health Laboratory for repeat investigations. Her blood and urine investigations were sent. Complete blood count findings revealed high red blood cell and white blood cell counts, a low mean corpuscular volume, and a high red cell distribution width-coefficient of variation. Other parameters, including serum electrolytes, renal function tests, liver function tests, and urine routine examinations, were within normal limits. A peripheral blood smear revealed microcytic hypochromic red cells with some target cells. Hemoglobin electrophoresis showed a very high percentage of hemoglobin E, a very low percentage of hemoglobin A2, and normal proportions of hemoglobin A and hemoglobin F. A diagnosis of homozygous hemoglobin E was made, and family screening was advised. Conclusions: Clinicians should be aware of the limitations of glycated hemoglobin estimation by ion exchange high-performance liquid chromatography in patients with hemoglobin E and other hemoglobin variants. If the clinical impression and glycated hemoglobin test results do not match, glycated hemoglobin values should be determined with a second method based on a different principle, and glycemic status should be confirmed through alternative investigations, preferably those that are not influenced by the presence of hemoglobin variants (for example, boronate affinity chromatography, fructosamine test, glycated albumin test, the oral glucose tolerance test, continuous glucose monitoring, etc.). Consistent or even doubtful results should also raise the suspicion of a hemoglobin variant, which should be confirmed through further evaluation and investigations. [ABSTRACT FROM AUTHOR]

Background: Modern treatments for transfusion-dependent β-thalassemia (TDβT) have allowed patients to reach high life expectancy with no iron overload. Despite survival improvement, atrial fibrillation (AF) has emerged as a relevant issue. AF pathophysiology and characteristics in TDβT are different than in the general population. Epicardial adipose tissue (EAT) may play a role but its relationship with AF in patients with TDβT has not been explored. Methods: A monocentric, cross-sectional study, enrolling consecutive patients with TDβT. Epicardial adipose tissue (EAT) was evaluated at magnetic resonance. Characteristics of patients with and without history of AF were investigated. Factors independently associated with AF prevalence were analyzed. Results: A total of 116 patients were enrolled. All patients were treated with regular chelation therapy. The prevalence of AF was 29.3% (34/116). Cardiac T2* and liver iron concentration were no different between patients with and without AF. EAT thickness was significantly higher in patients with AF at left atrium, right atrium and right ventricle (5.0 vs. 4.0 mm, p < 0.01, 4.4 vs. 4.0, p = 0.02 and 5.0 vs. 4.3, p = 0.04). Patients with AF presented with older age, (53 vs. 49 years, p < 0.01), more hypothyroidism (44.1 vs. 20.7%, p = 0.01), pulmonary hypertension (23.5 vs. 2.4% p < 0.01), splenectomy (88.2 vs. 64.6%, p = 0.01), higher right and left atrial volume (61 vs. 40 and 74 vs. 43 mL, both p < 0.01). At multivariable analysis, hypothyroidism, left atrial volume and left atrial EAT were independently associated with AF (odds ratio 9.95, 1.09 and 1.91, respectively). Conclusions: In a contemporary cohort of patients with TDβT, treated with regular chelation therapy, prevalence of AF was unrelated to iron overload. EAT was independently associated with AF. [ABSTRACT FROM AUTHOR]

The blood counts of α thalassemia carriers (α-thal) are similar to those of β thalassemia carriers, except for Hemoglobin A2 (Hb A2), which is not elevated. The objective of this study was to determine whether mathematical formulas are effective for detecting suspected α-thal. The data were obtained from the database of the prevention program for detecting couples at risk for having a child with hemoglobinopathy. Red Blood Cells (RBC) indices were analyzed using mathematical formulas, and the sensitivity and negative predictive value (NPV) were calculated. Among 1334 blood counts suspected of α-thal analyzed, only the Shine and Lal and the Support Vector Machine formulas revealed high sensitivity and NPV. Sensitivity was 85.54 and 99.33%, and NPV was 98.93 and 99.93%, respectively. Molecular defects were found in 291, and 81 had normal α genes. Molecular analysis was not performed in 962 of the samples. Based on these results, mathematical formulas incorporating one of these reliable formulas for detecting suspected α or β thalassemia carriers in the program of the automatic analyzers can flag these results, increase the awareness of the primary physicians about the carrier risk, and send an alert with a recommendation for further testing. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China. Patients and Methods: Routine blood evaluation, capillary electrophoresis of hemoglobin, and mutation of α - and β - thalassemia genes were evaluated in 19,976 individuals for thalassemia screening in Guizhou. Sanger sequencing of HBA1, HBA2 and HBB genes was performed in samples with abnormal bands or unexplained increases of normal bands. The types of abnormal hemoglobin were obtained by sequence analysis. Results: Abnormal hemoglobin was detected in 84 individuals (detection rate, 0.42%). Ten types each of α and β globin chain variants were detected, including most commonly Hb E, Hb New York and Hb Port Phillip. In this study, the abnormal Hb Mizuho was identified for the first time in a Chinese population, and a novel abnormal hemoglobin Hb Guiyang (HBA2: c.151C > A) was detected for the first time. Except for Hb Mizuho, other abnormal hemoglobin heterozygotes without thalassemia or iron deficiency had no significant hematological changes. Conclusion: This study enriched the molecular epidemiological data of abnormal hemoglobin in Guizhou, China and provided reference data for genetic counseling and prenatal diagnosis of abnormal hemoglobin. [ABSTRACT FROM AUTHOR]

The hemoglobin (Hb) variants are qualitative abnormalities due to production of structurally abnormal globin proteins. They are categorized based on the type of mutation present in the α1, α2, β, Gγ, Aγ and δ globin genes. So far, more than 1550 Hb variants are reported in the database. They could lead to Hb polymerization, Hb instability, altered oxygen affinity and decreased oxygen‐carrying capacity of Hb or have no clinical manifestations. In India, ethnic diversity, consanguinity, regional variations and migration result in the presence of different Hb variants. We have compiled all the variants of α, β and δ globin chains in heterozygous, homozygous and in compound heterozygous forms reported from India in the last 52 years. Of the 63 rare and novel hemoglobin variants reported from India, 22 were α‐globin chain variants, 37 were β‐globin chain variants and 4 were δ‐globin chain variants. Twelve novel Hb variants (Hb J Rajappan, Hb Koya Dora, Hb Rampa, Hb Godavari, Hb Chandigarh, Hb D Agri, Hb Lucknow, Hb Vellore, Hb Midnapore, Hb Bijnor, Hb A2Tianhe and Hb A2Saurashtra) were identified among persons of Indian origin. Majority of them were picked up on HPLC. Some of the variants like Hb Titusville, Hb Shimonoseki, Hb Chandigarh, Hb D Agri, Hb Yaizu and Hb Vellore eluted in the HbS window whereas variants like HbD Iran, Hb St. Louis, Hb G Coushata, HbM Saskatoon, Hb Lucknow, Hb Grange‐Blanche and Hb Tianshui showed falsely elevated HbA2. Hence, careful and systematic investigations are required to identify them. [ABSTRACT FROM AUTHOR]

Sickle cell disease (SCD) occurs in 2.8 % of our Jamaican antenatal population with homozygous HbSS being most associated with adverse maternal and perinatal outcomes. A retrospective comparative analysis of HbSS, HbSC and HbSβThal pregnancy outcomes at the University Hospital of the West Indies (UHWI) between January 2012 and December 2022 was conducted. Of 120 patients (138 pregnancies), obesity occurred in 36 % (20/56) of the 'non-HbSS' group, i.e. HbSβThal (55 %, 5/9) and HbSC (32 %, 15/47) combined vs. 9.7 % of the HbSS (8/82). HbSS patients had more crises requiring transfusions, acute chest syndrome (ACS), maternal 'near-misses' (OR=10.7, 95 % 3.5–32.3; p<0.001), hospitalizations (OR 7.6, 95 % CI 3.4–16.9; p<0.001), low birth weight (LBW) neonates (OR 3.1, 1.1–8.9; p=0.037) and preterm birth (OR=2.6, 1.2–5.8; p=0.018) compared to HbSC and HbSβThal. Low dose aspirin was prescribed in 43 %. Logistic regression showed those NOT on aspirin (n=76) had more miscarriages (22 v. 2 %), were LESS likely to have a live birth (75 v. 95 % (0.2, 0.04–0.57, p=0.005)), but surprisingly had fewer painful crises (28 v. 46 % (0.5, 0.03–0.9, p=0.03)). HbSS women had a 10-fold excess of maternal near-misses. Additional research may further clarify the effects of aspirin on pregnancy outcomes as related to SCD genotypes. [ABSTRACT FROM AUTHOR]

There is a rare subset of patients with a genetically abnormal hemoglobin structure initially discovered in the Volga region of Europe known as Volga anemia. Key features of this condition include compromised delivery of oxygen to peripheral tissues and altered red blood cells that have a higher likelihood of being broken down or hemolyzed, which can lead to significant hemolytic anemia. Methylene blue is a dye that acts as a reducing agent of oxygen and is commonly used in toxic states that lead to methemoglobin build‑up. This paper explores the pathophysiology of this genetic condition and documents three cases across two patients—a father and son—when methylene blue was used during an anemic crisis. [ABSTRACT FROM AUTHOR]

Hemoglobinopathies, including thalassemia and hemoglobin (Hb) variants, are common hematological disorders in tropical countries. Accurate and precise separation of hemoglobin types and reliable quantitation are necessary for differential diagnosis of these disorders. We have evaluated the analytical performances of premier resolution-high-performance liquid chromatography (PR-HPLC; Trinity Biotech, Co. Wicklow, Ireland) to assist in the presumptive diagnosis of thalassemia and Hb variants commonly found in Southeast Asian countries. HbA0, HbA2, HbE, and HbF levels were separated and quantified in 120 blood samples from unrelated adult subjects and compared with those analyzed by capillary zone electrophoresis (CZE; CAPILLARYS™ 2, Sebia, Norcross, GA, US). The Hb analysis patterns of Hb variants obtained from the PR-HPLC system were also compared to those obtained from HPLC (VARIANT II, β-thalassemia Short Program, Bio-Rad, Laboratories, Hercules, CA, US) and CZE systems. The PR-HPLC had excellent precision with a coefficient of variation (CV) for HbA2 quantitation of 3.8 % within-run and 5.2 % between-run. The levels of HbA2/E quantified by the PR-HPLC system correlated well with those of the CZE system (r=0.997). In addition, thalassemia interpretation results obtained from the PR-HPLC and the CZE showed 100 % agreement. Moreover, chromatograms of the PR-HPLC were also comparable to those of VII-HPLC and CAP2-CZE electropherograms. The PR-HPLC system would be applicable to diagnose common forms of thalassemia and Hb variants in Southeast Asia. [ABSTRACT FROM AUTHOR]

Anemia is a condition in which the number of red blood cells or the hemoglobin concentration within them is lower than normal. Thalassemia is a Mutation of the globin gene that can cause changes in the globin chain, e.g. structural hemoglobinopathy or changes in the rate of synthesis or the production ability of certain globin chains. Epidemiological research in Indonesia found that the frequency of the beta thalassemia gene ranges from 3-10%. Case report of patient Mrs. T, 27 years old, HPHT: 01-10-2023, routine ANC examination every month, ANC examination results in 18- 19 weeks no complaints, and laboratory examination results in Hb 4.7. Patients with thalassemia beta major and intermediate need to be given regular transfusions and keep their hemoglobin levels above 10 mg/dl. All patients with homozygous thalassemia should receive folic acid supplements. [ABSTRACT FROM AUTHOR]

Introduction: HbC is a common structural hemoglobinopathy especially in West Africa. Prevalence and regional distribution of HbC in Saudi Arabia are widely undocumented. Patients with homozygous HbC disease may have mild hemolytic anemia whereas combination with hemoglobin S (HbS) leads to a clinically severe phenotype. Aim: The current epidemiological study, considered the largest from Saudi Arabia, aimed to evaluate the regional prevalence of the HbC variant among the couples participating in the premarital screening program from 2011 to 2018. Methods: Data from the PMSGC program were obtained for premarital screening and genetic counseling. The collected data were then entered into the SEHA platform, a centralized electronic repository for the 13 designated regions in Saudi Arabia. Hemoglobin electrophoresis samples are analyzed using either HPLC, capillary electrophoresis, or a combination of both methods to confirm the presence of abnormal hemoglobin bands. Results: This study included 1,871,184 individuals from 2011 to 2018. Of those, 49.8% were males and 50.2% were females. 112,618 (6.0%) had an abnormal test. Total number of Hb C cases were 778 (0.04%). HbC trait (HbAC) was detected in 764 participants while homozygous HbC (HbCC) and combined heterozygous (HbSC) were found in 9 and 5 cases, respectively. The regions near the Red Sea have higher rates than the central and eastern regions. Conclusion: HbC is a rare variant in Saudi Arabia with varying regional frequencies. HbC variant is more common in Mecca and Madina regions. The geographic area of HbC distribution differs from the areas with high prevalence of HbS, which explains why HbSC disease cases are overwhelmingly rare. [ABSTRACT FROM AUTHOR]

Background: Hemoglobin (Hb) SD-Punjab is a rare Hb disorder which may present at any age ranging from infancy to adulthood with variable clinical severity. There are very few reports of HbSD-Punjab with stroke, leading to moyamoya syndrome. We report two siblings with HbSD-Punjab, their diagnosis, genotype–phenotype correlation, and management. Clinical Description: Two siblings, ages 6 and 4 years, presented together to the emergency for the first time with different manifestations. The elder child had fever and acute onset right-sided weakness with anemia and splenomegaly, whereas the younger sister presented with fever and decreased appetite with anemia and splenomegaly. Management and Outcome: Both siblings showed severe anemia with the second sibling showing low platelet counts also. Magnetic resonance imaging of the brain of the elder sister showed chronic infarcts in the left frontal region in addition to acute infarction in the left cerebral hemisphere with angiography suggestive of moyamoya disease. Both siblings had blood pictures suggestive of hemolytic anemia and Hb electrophoresis showed co-inheritance of HbSD-Punjab. Both siblings responded to supportive treatment and blood transfusions and were started on oral hydroxyurea. At the genotype level, a combination of factors was noted with normal α-gene copies known to increase severity and heterozygosity for Xmn1 polymorphism explaining the higher HbF levels which decrease severity. Conclusion: Knowledge of the varied clinical presentation of hemolytic disorders and early detection is key to prevent more severe sequelae in such disorders.

Abstract Background Screening for sickle cell traits before marriage or producing children is one of the outstanding preventive measures for sickle cell disease (SCD).The disease is a collection of inherited blood disorders that impact millions globally, with a predominant 75% occurrence in the sub-Saharan region. With increasing burden of SCD on the continent amidst a cost effective prevention method, no study has systematically reviewed or presented meta-analytic uptake or practice of premarital sickle cell trait screening. Methods This review systematically explored the uptake or practice of premarital genotype screening in Africa. We searched PubMed and Scopus databases for African studies on premarital screening for sickle cell traits. Results Our results indicate that the pooled uptake of premarital sickle cell trait screening in Africa is 47.82% (95% CI: [46.53–49.11]; I2: 98.95% [98.74–99.13]). Our review observed, a significant relationship between the awareness of sickle cell disease and the uptake of genotype screening; F(1, 13) = 12.04, p = 0.004). The model explained approximately 48.08% of the variation in genotype screening (R² = 0.4808) and predicted a 0.729 increase in the likelihood of genotype screening uptake for every unit rise in sickle cell disease awareness (β = 0.729, p = 0.004). Additionally, Pearson correlation (r = 0.6934) indicated a moderately strong positive correlation between the two variables. Conclusion With over 75% of the global burden of sickle cell disease domiciled in Africa, the continent cannot overlook the cost of hemoglobinopathies. The uptake of sickle cell traits screening is suboptimal across the continent. To achieve the mandate of sustainable development goal number (3); to end preventable deaths of newborns and children under 5 years of age by 2030, there is need to intensify campaigns on premarital genetic screening through education and other health promotion tools.

Roszymah Hamzah,1 Ahmad Sabry Mohamad,2 Norafiza Mohd Yasin,3 Ezalia Esa,3 Guo Chen,4 Veena Selvaratnam1 1Hematology Department, Ampang Hospital, Ampang, Selangor, Malaysia; 2Medical Engineering, Universiti Kuala Lumpur-British Malaysian Institute, Gombak, Selangor, Malaysia; 3Institute for Medical Research, Ministry of Health, Shah Alam, Selangor, Malaysia; 4Beam Therapeutics Inc., Cambridge, MA, USACorrespondence: Ahmad Sabry Mohamad, Medical Engineering, Universiti Kuala Lumpur-British Malaysian Institute, Bt.8, Jln Sg. Pusu, Gombak, Selangor, 53100, Malaysia, Email sabry@unikl.edu.myBackground: Human hemoglobin of G-Makassar and hemoglobin E (Hb E) are hemoglobin variants that affect Beta (β) globin. Hb G-Makassar is a very rare variant while Hb E is estimated to affect at least one million people worldwide. Both Hb G-Makassar and Hb E can be inherited in the heterozygous, homozygous or compound heterozygous state. This case series describes the characteristics of four individuals with compound heterozygosity for Hb G-Makassar/Hb E cases in Malaysia. To the best of our knowledge, these are the only four individuals with this genotype reported in the literature.Case Series: We present four cases of compound heterozygosity for Hb G-Makassar/Hb E identified from October 2014 to January 2021. All the cases were incidental findings whereby the screening Hb analysis showed the presence of peaks in both Hb S and Hb E zones on capillary electrophoresis (CE) and cation-exchange high-performance liquid chromatography (HPLC). Molecular analysis confirmed the findings of compound heterozygous Hb G-Makassar/Hb E. Two cases had a history of anemia secondary to unrelated conditions that resolved with treatment of the underlying cause. The other two cases were asymptomatic individuals who were detected through Malaysia’s National Thalassemia Screening program. On the last follow-up, all the individuals were well, non-transfusion dependent, and had no reported history of chronic anemia, bleeding, hemolysis or thromboembolism complications.Conclusion: The cases reported here highlight the possibilities for rare compound heterozygous states in multi-ethnicity populations such as Malaysia. Compound heterozygous Hb G-Makassar/Hb E individuals are clinically silent with laboratory values suggesting microcytic and hypochromic red blood cells. Further local epidemiology or population studies with genotyping tests are required for a better understanding of the diversity of its clinical phenotype.Keywords: beta-thalassemia, compound heterozygous, Hb E, Hb G-Makassar, hemoglobinopathy

Purpose:This study aimed to determine the atypical localizations of extramedullary hematopoiesis (EMH) in patients with hemolytic anemia, most of whom were diagnosed with hemoglobinopathy and are followed in our region. Materials and Methods: The files and imaging examinations of hemolytic anemia patients in the Pediatric Hematology Clinic of our hospital between 01.07.2020-28.02.2022 were retrospectively scannedPatients who were imaged for complaints or for other reasons were evaluated for lesions. Some of the patients were over the age of 18 and the cases were mostly detected at this age. Results: A total of 247 patients were scanned in the study, and EMH was detected in atypical localization in 5 patients as a result of imaging studies, firstly with lung films and then with more advanced methods (such as chest computed tomography, magnetic resonance imaging) when necessary. Unilateral or bilateral thoracic paraspinal EMH was detected in the patients. One patient had an additional right kidney EMH focus. Conclusion: Clinical and radiological evaluation of the probability of a mass lesion detected in patients with hemolytic anemia to be EMH at atypical localization will protect the patient from unnecessary diagnostic and interventional procedures. During the regular follow-up and treatment of the patients, the presence of these lesions should also be predicted.

Thalassemia is the most common monogenic disease in Asia, including Indonesia that causes burdens for the government, patients, and families. As the sixth most non-communicable disease, thalassemia utilized IDR 600 billion in 2022 for more than 300 thousand cases. With, 3.8% of Indonesians carrying a mutation of thalassemia on their globin gene, this economic burden is projected will increase if no actions are taken. On the other hand, child marriage is reported to increase every year, including among orphans. Without proper knowledge and genetic testing on thalassemia, child marriage might contribute to the increasing of thalassemia patients. Thus, increasing knowledge on thalassemia among orphan adolescents is important. This community development uses several methods, including seminar, discussion, book, and poster, targeting the orphan adolescents (n= 40) in Mojokerta, East Java. A questionnaire on thalassemia was used to measure the knowledge, before and after the activity. The results show that the respondents have a moderate knowledge about thalassemia (median= 4 (0-9)), and increase to median=9 (3-10)) after the activities (p< 0.001). Even though overall knowledge is increased, several information including thalassemia is a genetic disease, not similar to blood cancer, not the only type of anemia (Q6), and how to diagnose thalassemia (Q9) still need to be emphasized. Taken together, direct and indirect approaches, such as seminar, discussion, book, and poster are effective in increasing thalassemia knowledge among orphan adolescents. These activities are more effective in targeting late adolescents, compared to early and middle adolescents. However, more effective methods are necessary to target Generation Z who are more familiar with the internet.

Background Inherited hemoglobin disorders are common in clinical practice. While qualitative (i.e. sickle cell disease) and quantitative (thalassemia) hemoglobinopathies are usually diagnosed clinically and confirmed through simple laboratory assessments, hemoglobin variants with altered oxygen affinity often go undetected due to their typically silent clinical presentation. Hemoglobin (Hb) J-Auckland, a low oxygen affinity hemoglobin variant first described in 1987 in Auckland, New Zealand, is one such silent disorder.Case presentation We report for the first time a clinically evident case of previously undiagnosed Hb J-Auckland in an 8-year-old girl who presented with unexplained hypoxemia at high altitude. Her oxygen level was corrected with supplemental oxygen and when assessed at low altitude. A brief discussion of the diagnostic approach and clinical implications is provided.Conclusion Standard hemoglobin analysis is essential for the evaluation of suspected altered affinity hemoglobinopathy, and genetic testing is often required for definitive diagnosis. Early recognition and diagnosis of these variants can prevent mismanagement and improve patient outcomes.

Background: Screening for sickle cell traits before marriage or producing children is one of the outstanding preventive measures for sickle cell disease (SCD).The disease is a collection of inherited blood disorders that impact millions globally, with a predominant 75% occurrence in the sub-Saharan region. With increasing burden of SCD on the continent amidst a cost effective prevention method, no study has systematically reviewed or presented meta-analytic uptake or practice of premarital sickle cell trait screening. Methods: This review systematically explored the uptake or practice of premarital genotype screening in Africa. We searched PubMed and Scopus databases for African studies on premarital screening for sickle cell traits. Results: Our results indicate that the pooled uptake of premarital sickle cell trait screening in Africa is 47.82% (95% CI: [46.53–49.11]; I2: 98.95% [98.74–99.13]). Our review observed, a significant relationship between the awareness of sickle cell disease and the uptake of genotype screening; F(1, 13) = 12.04, p = 0.004). The model explained approximately 48.08% of the variation in genotype screening (R² = 0.4808) and predicted a 0.729 increase in the likelihood of genotype screening uptake for every unit rise in sickle cell disease awareness (β = 0.729, p = 0.004). Additionally, Pearson correlation (r = 0.6934) indicated a moderately strong positive correlation between the two variables. Conclusion: With over 75% of the global burden of sickle cell disease domiciled in Africa, the continent cannot overlook the cost of hemoglobinopathies. The uptake of sickle cell traits screening is suboptimal across the continent. To achieve the mandate of sustainable development goal number (3); to end preventable deaths of newborns and children under 5 years of age by 2030, there is need to intensify campaigns on premarital genetic screening through education and other health promotion tools. [ABSTRACT FROM AUTHOR]