Inherited Hemoglobin Disorders Research Articles

Constructing a novel clinical indicator model to predict the occurrence of thalassemia in pregnancy through machine learning algorithm

Thalassemia is one of the inherited hemoglobin disorders worldwide, resulting in ineffective erythropoiesis, chronic hemolytic anemia, compensatory hemopoietic expansion, hypercoagulability, etc., and when a mother carries the thalassemia gene, the child is more likely to have severe thalassemia. Furthermore, the economic and time costs of genetic testing for thalassemia prevent many thalassemia patients from being diagnosed in time. To solve this problem, we performed least absolute shrinkage and selection operator (LASSO) regression to analyze the correlation between thalassemia and blood routine indicators containing mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red blood cell (RBC). We then built a nomogram to predict the occurrence of thalassemia, and receiver operating characteristic (ROC) curve was used to verify the prediction efficiency of this model. In total, we obtained 7,621 cases, including 847 thalassemia patients and 6,774 non-thalassemia. Among the 847 thalassemia patients, with a positivity rate of 67.2%, 569 cases were positive for α-thalassemia, and with a rate of 31.5%, 267 cases were positive for β-thalassemia. The remaining 11 cases were positive for both α- and β-thalassemia. Based on machine learning algorithm, we screened four optimal indicators, namely, MCV, MCH, RBC, and MCHC. The AUC value of MCV, MCH, RBC, and MCHC were 0.907, 0.906, 0.796, and 0.795, respectively. Moreover, the AUC value of the prediction model was 0.911. In summary, a novel and effective machine learning model was built to predict thalassemia, which functioned accurately, and may provide new insights for the early screening of thalassemia in the future.

Characterization of New Alpha Zero (α0) Thalassaemia Deletion (--GB) among Malays in Malaysian Population.

Malaysia is a multicultural and multiethnic country comprising numerous ethnic groups. From the total population of 32.7 million, Malays form the bulk of the Bumiputera in Malaysia comprise about 69.9%, followed by Chinese 22.8%, Indian 6.6%, and others 0.7%. The heterogeneous population and increasing numbers of non-citizens in this country affects the heterogeneity of genetic diseases, diversity, and heterogeneity of thalassaemia mutations. Alpha (α)-thalassaemia is an inherited haemoglobin disorder characterized by hypochromic microcytic anaemia caused by a quantitative reduction in the α-globin chain. A majority of the α-thalassaemia are caused by deletions in the α-globin gene cluster. Among Malays, the most common deletional alpha thalassaemia is -α3.7 deletion followed by --SEA deletion. We described the molecular characterization of a new --GB deletion in our population, involving both alpha genes in cis. Interestingly, we found that this mutation is unique among Malay ethnicities. It is important to diagnose this deletion because of the 25% risk of Hb Bart's with hydrops fetalis in the offspring when in combination with another α0- thalassaemia allele. MLPA is a suitable method to detect unknown and uncommon deletions and to characterize those cases which remain unresolved after a standard diagnostic approach.

Prevalence and Risk Factors of Stroke Among Children With Sickle Cell Disease: A Retrospective Study at a Tertiary Care Center.

Background Sickle cell disease (SCD) is a common autosomal recessive inherited hemoglobin disorder in many countries. Neurological complications are among the most disabling complications in SCD. Stroke and cerebral vasculopathy can lead to further neurological insult. Ischemic insults, stroke, and silent infarcts are preventable causes of morbidity and mortality in SCD patients. Understanding the epidemiology and characteristics of such patients will help to prevent complications. Methodology This is aretrospective studyconducted in a tertiary care center in Saudi Arabia. Cases of SCD admitted to the pediatric ward between the years 2019to 2023were included in the study.Demographic data, clinical diagnosis, and frequency of prior admissions were collected. Brain imaging results were reviewed and included. Furthermore, the study assessed common risk factors leading todeveloping astroke in SCD pediatric patients. Risk factors and clinical outcomes after stroke were also included. Results Eighty-one patients were enrolled. The mean age of stroke patients was 8.21±3.50 years while the mean age of non-stroke patients was 6.24±3.76 years. More than half of the patients were females in both the stroke (61.50%) and non-stroke groups (52.90%). ThirteenSCDpatients (16%) were diagnosed with stroke. Previous history of stroke, high mean corpuscular volume (MCV), and low red blood cells count (RBC) were statistically significant risk factors for stroke (p<0.0001), (p<0.0001), (p<0.03),respectively. Conclusion Stroke is one of the most devastating complications of SCD. The prevalence of stroke among SCD patients in our study was 16%. Transcranial Doppler ultrasound screening is the most important predictor of stroke.

Types of Inherited Hemoglobin Disorders Among the Patients Attending Hematology Outdoor of a Tertiary Care Hospital in Bangladesh

Background: Inherited Haemoglobin (Hb) disorders are the most frequent genetic hereditary disorders with an increasing global health burden, especially in low- and middle-income countries. This disorder is mostly caused by a point mutation on a globin gene resulting mostly in single amino acid substitutions and consequently defective globin chain production or reduced production of normal haemoglobin. Despite the limited study of this country regarding this issue, the number of individuals suffering from inherited Hb disorders is not negligible. Thus, the study was designed to evaluate the types of inherited haemoglobin disorders among the patients attending the haematology outdoor of Dhaka Medical College Hospital (DMCH). Methods: This hospital-based cross-sectional study was conducted at the Department of Haematology in DMCH, for a period of 6 months (June 2022 to November 2022. People attending the Haematology outpatient department and diagnosed with a case of inherited Hb disorder were approached for inclusion. Written informed consent was taken from each subject. Ethical issues were ensured properly. For the study, a total of 100 patients were interviewed for less than 30 minutes of duration in each case. Relevant investigations such as, Hemoglobin (Hb), Red Cell Count (RCC), MCV, MCH, MCHC, RDW, Reticulocyte, Serum ferritin were done in the Haematology lab of DMCH, and data were collected in a semi-structured questionnaire. Collected Data were analyzed by SPSS 21. Results: Out of 100 inherited Hb disorder subjects, the majority (60 or 60%) were from the age group of 14 to 24 years. The mean age of patients was 38.78 ± 6.09 with range 15-51 years. The male-female ratio was 1:1. The majority (58%) came from rural areas and 42% came from urban areas. Mean value of Hb was 10.54; subsequently, MCV (63.25), MCH (22.18), S ferritin (140.43). The majority of patients had their onset of clinical presentation of illness for 5 years. Among total subjects, two-thirds of the patients (66 or 66%) had Hb E Disease followed by 14% Beta thalassaemia trait, 14% Hb E trait, and 6% b thalassaemia major. No association was noted between the type of thalassaemia with age &amp; sex of the subjects. Conclusion: Irrespective of age and sex variations, Hb E disease is the most frequent inherited haemoglobin disorder among the patient attending the haematology outdoor of a tertiary care hospital. J MEDICINE 2023; 24(2): 96-105

Anemia in an ethnic minority group in lower northern Thailand: A community-based study investigating the prevalence in relation to inherited hemoglobin disorders and iron deficiency.

Anemia is a globally well-known major public health problem. In Southeast Asia where there is ethnic diversity, both iron deficiency (ID) and inherited hemoglobin disorders (IHDs) are prevalent and are considered to be the major factors contributing to anemia. However, little is known about the anemia burden among the ethnic minorities. In this study, we determine the burden of anemia, in relation to ID and IHDs, among the Karen ethnic minorities living in the rural area of lower northern Thailand. A cross-sectional community-based study was conducted at Ban Rai district, Uthai Thani province. Study participants included 337 Karen people aged over 18 years. Socio-economic and health-related information were obtained through interviews and recorded by local health staff. Anemia, IHDs and ID were diagnosed according to standard laboratory methods. Multivariate logistic regression analysis was applied to identify risk factors of moderate-to-severe anemia. The prevalence of overall anemia was 27.9% (95% CI = 23.2-33.0). Mild and moderate anemia were detected in 18.7% (95% CI = 14.7-23.3) and 8.9% (95% CI = 6.1-12.5) respectively. Severe anemia was found in one case (0.3%). Various forms of IHDs were identified in 166 participants, constituting 49.3% (95% CI = 43.8-54.7). The most common form of IHDs was α+-thalassemia (32.9%), followed by β-thalassemia (12.2%), α0-thalassemia (4.2%), hemoglobin E (3.9%), and hemoglobin Constant Spring (0.9%). Among 308 participants who were investigated for ID, the prevalence was discovered to be 6.8% (95% CI = 4.3-10.2). Analysis of risk factors of moderate-to-severe anemia revealed that individuals with ID, β-thalassemia and age > 65 years were at high risk with adjusted odds ratio of 17 (95% CI = 3.8-75.2), 6.2 (95% CI = 1.4-27.8) and 8.1 (95% CI = 1.6-40.4) respectively. Anemia among the Karen is of public health significance; and IHDs are the major contributing factors. Because of the high risk of developing moderate-to-severe anemia, special attention should be paid to individuals affected with ID, β-thalassemia and the elderly. Public awareness of the health burden of severe thalassemia syndromes should also be campaigned.

Diagnosis of α-thalassaemia by colorimetric gap loop mediated isothermal amplification

α-Thalassaemia is an inherited haemoglobin disorder that results from the defective synthesis of α-globin protein. Couples whom both carry the α-thalassaemia 1 gene are at risk of having a foetus with the most severe thalassaemia, Hb Bart’s hydrops fetalis, with a risk of maternal mortality. However, haematological parameters alone cannot distinguish between a α-thalassaemia 1 carrier and a homozygous α-thalassaemia 2, in which one α-globin gene has been deleted on each chromosome. A rapid and accurate molecular detection assay is essential for prevention of the disease in populations where α-thalassaemia 1 is common. Multiplex Gap-PCR analysis is widely used for diagnosis of α-thalassaemia. However, the technique requires a thermocycler and post-amplification processing, which limits its application in primary care or in rural areas in developing countries. Loop mediated isothermal amplification (LAMP) amplifies target DNA at a constant temperature and does not require a thermocycler. This study developed a colorimetric Gap-LAMP using malachite green to allow naked eye visualization of two deletional α-thalassaemia 1 commonly found in Asian populations, the Southeast Asian type (--SEA) and the Thai type (--THAI) deletions. The Gap-LAMP was performed on DNA samples from 410 individuals carrying various α-thalassaemia gene defects with 100% concordance with conventional Gap-PCR analysis. This method eliminates post-amplification processing or the use of expensive sophisticated equipment and allows screening large populations for the prevention and control of α-thalassaemia.

DIAGNOSTIC ACCURACY OF RDWI TO DIFFERENTIATE IRON DEFICIENCY ANEMIA AND THALASSEMIA TRAIT IN BORDERLINE HBA2

Background: Thalassemia is an inherited hemoglobin disorders in which there is reduction or absence of α or β chains due to mutations in α or β genes. Microcytic hypochromic anemia is hallmark of beta thalassemia trait and the patient is usually asymptomatic. It is important to differentiate it from iron deficiency anemia (IDA) which also shows similar peripheral blood picture. The diagnosis is based on quantification of HbA2 and serum ferritin. If the level of HbA2 is more than 3. 5%, then diagnosis of beta thalassemia trait is made. The problem arises with borderline HbA2 i. e 3.1% - 3.4%. There is also diagnostic difficulty when concomitant iron deficiency anemia is present.&#x0D; Objectives: To determine the diagnostic accuracy of RDWI in borderline HbA2 to distinguish the beta thalassemia trait from IDA and to diagnose beta thalassemia trait when genetic analysis is not easily available.&#x0D; Methods: It was a cross sectional validation study. A total of 90 patients were included in this study, having HbA2 between 3.1-3.4%. Tests for serum ferritin, serum iron and total iron binding capacity (TIBC) were done on all samples. RBC morphology, RBC count, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC) and RDW of all samples were noted. RDWI of all samples was calculated. Mutational analysis by ARMS- PCR was done for confirmation of β thalassemia trait.&#x0D; Results: Out of 90 samples with borderline HbA2, 30 cases were diagnosed as β thalassemia trait. Out of these, 15(50 %) had concomitant IDA along with beta thalassemia trait and 15 were non iron deficient beta thalassemia carriers. 43 samples were not iron deficient and were also negative for β thalassemia trait, whereas 17 samples had only IDA without beta thalassemia trait. The sensitivity of RDWI was 76.6% and specificity was 56.6% in borderline HbA2.&#x0D; Conclusion: RDWI is a good indicator to differentiate between IDA and beta thalassemia trait (sensitivity 76.6% specificity 56.6%). But in all cases of borderline HbA2 genetic analysis should be done to see the mutation and to confirm the diagnosis.

Current Evidence and Rationale to Guide Perioperative Management, Including Transfusion Decisions, in Patients With Sickle Cell Disease.

Sickle cell disease (SCD) is a collection of inherited hemoglobin disorders that results in chronic hemolytic anemia, vaso-occlusion, pain, and end organ damage. Surgery in the SCD population requires careful planning, as perioperative stressors can lead to increased sickling and risk of inducing or further exacerbating vaso-occlusive episodes (VOEs). Additionally, the underlying hypercoagulability and immunocompromised state due to SCD places patients at increased risk of both venous thromboembolism and infection. Judicious fluid administration, temperature regulation, thorough preoperative and postoperative analgesic planning, and preoperative transfusion are all crucial components of decreasing risks of surgery in patients with SCD.

Spectrum of Thalassemia and Hemoglobinopathy Using Capillary Zone Electrophoresis: A Facility-Based Single Centred Study at icddr,b in Bangladesh

Background: Although the global thalassemia zone covers Bangladesh, there are very limited studies conducted in this region. Therefore, the focus of our study is to understand the prevalence and burden of thalassemia and hemoglobinopathy in Bangladesh. Methods: The analysis was based on a retrospective evaluation of laboratory diagnoses between 2007 January and 2021 October. A total of 8503 specimens were sampled and analyzed which were either referred by corresponding physicians or self-referred. This was neither any epidemiological nationwide survey nor was the study population chosen randomly. Hematological data were obtained through capillary zone electrophoresis and corresponding complete blood count. Results: 1971 samples (~23.18% of the total) were found with at least one inherited hemoglobin disorder. The most common hemoglobin disorder observed was the hemoglobin E (Hb E) trait (10.67%), followed by the β-thalassemia trait (8.4%), homozygotic Hb E (1.59%), and Hb E/β-thalassemia (1.58%). Other variants found in this study with minimal percentages were Hb N-Seattle, Hb S, Hb D-Punjab, Hb Lepore, Hb C, Hb Hope, Hb H, and hereditary persistence of fetal hemoglobin. Discussion: The pattern of thalassemia and hemoglobinopathy in our study is diverse and heterogeneous. A broad and detailed spectrum of such inherited hemoglobin disorders will ultimately be helpful in implementing nationwide thalassemia management and strategy policy in Bangladesh.

Effect of Bone Pain Vaso-occlusive Crises on Red Blood Cell Parameters of Sickle Cell Anaemia Patients

Background: Sickle Cell Anaemia (SCA) is an inherited haemoglobin disorder characterized by shortened red cell life span and altered red blood cell parameters due to the red cell sickling, vaso-occlusion and chronic haemolysis occasioned by the disease. The occurrence of bone pain vaso-occlusive crises may further alter these parameters; an occurrence that highlights on the pathophysiology of SCA and worth noting in the management of affected patients. Aims and Objectives: This study was performed to determine the effect of bone pain vaso-occlusive crises on red blood cell parameters of SCA patients. Study Design: A longitudinal study. Settings: Fifty SCA patients receiving care at a tertiary hospital in Sokoto, Nigeria were consecutively enrolled while in their steady clinical state and followed up till when they re-presented during the bone pain vaso-occlusive crises state. Materials and Methods: Structured proforma was used for clinical data capturing while red blood cell parameters (red blood cell count (RBC), haemoglobin (Hb) concentration, haematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and red cell distribution width (RDW) were determined via automation using Nortek 3-part haematology analyser. Leishmann stained peripheral blood smears were examined to cross-check morphological details of the red blood cells. Statistics: Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 21.0 (IBM Corp, Armonk, NY, USA) and further summarized as means ± standard deviations. Comparison of means was performed using paired sample t-test and Anova as appropriate while Pearson’s test was used for correlation analysis. Results were presented in tables while statistical significance was set at p&lt;0.05. Results: Fifty SCA patients were enrolled for the study and consisted of 26 (52%) females and 24 (48%) males. The overall mean age of the study participants was 22.82 ± 6.55 years with the minimum and maximum ages of 18 and 42 respectively. During the bone pain vaso-occlusive crises, 14 (28%), 21 (42%) and 15 (30%) of the patients had mild, moderate and severe bone pains respectively. The red blood cell parameters during the steady and bone pain crises states were RBC count (2.87±0.69 vs. 2.93±0.83; p=0.675); HCT (24.33±5.01 vs. .37±5.61; p=0.373); Hb concentration (8.34±1.53 vs. 7.99±1.54; p=0.228); MCV (87.87±9.13 vs. 82.59±14.64; p=0.021); MCH (29.76±5.61 vs. 30.48±13.54; p =0.729); MCHC (32.89±4.76 vs. 32.10±3.75; p=0.394) and RDW-CV (19.30±6.58 vs. 19.59±5.27; p=0.829) respectively. During bone pain vaso-occlusive crises, the red blood cell parameters based on mild, moderate and severe pains were RBC count (2.82±0.88 vs. 2.78±0.57 and 3.06±0.65; p=0.472); HCT (24.29±6.37 vs. 24.11±5.12 and 24.68±3.53; p=0.947); Hb concentration (8.46±2.01 vs. 8.33±1.57 and 8.24±0.92; p=0.927); MCV (87.60±7.46 vs. 91.03±9.21 and 83.69±9.22, p=0.055); MCH (31.28±7.77 vs. 30.27±4.27 and 27.61±4.51; p=0.185); MCHC (33.05±7.54 vs. 33.07±3.39 and 32.48±3.13; p=0.928) and RDW-CV (19.61±9.65 vs. 19.96±5.61 and 18.10±4.23; p=0.700) respectively. Conclusions: Of all the studied red cell parameters, only MCV significantly differ between the steady and bone pain crises states of SCA. A drop in MCV was recorded during the bone pain crises; probably reflecting depletion of the large reticulocytes and neocytes during the accentuated red cell sickling and vaso-occlusive events characteristic of this clinical state.

Single-cell profiling of ineffective erythropoiesis in a mouse model of β-thalassaemia intermedia.

Beta-thalassaemia is an inherited haemoglobin disorder characterised by ineffective erythropoiesis (IE). The detailed pathogenesis of IE remains unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to examine IE in Th3/+ β-thalassaemic mice. The results showed that the erythroid group was remarkably expanded, and genes involved in biological processes such as iron metabolism, haeme synthesis, protein folding, and response to heat were significantly upregulated from erythroid progenitors to reticulocytes in β-thalassaemic mice. In particular, we identified a unique cell population close to reticulocytes, named ThReticulocytes, characterised by a high level of heat shock protein 70 (Hsp70) expression and dysregulation of iron metabolism and haeme synthesis signalling. Treatment of β-thalassaemic mice with the haeme oxygenase inhibitor tin-mesoporphyrin effectively improved the iron disorder and IE, and the ThReticulocyte population and Hsp70 expression were significantly suppressed. This study revealed in detail the progression of IE at the single-cell level and possibly provided clues to find therapeutic targets in thalassaemia.

Outcomes of Pregnancy in Sickle Cell Disease Patients: Results from the Prospective ESCORT-HU Cohort Study.

Sickle cell disease (SCD) refers to a group of inherited hemoglobin disorders in which sickle red blood cells display altered deformability, leading to a significant burden of acute and chronic complications, such as vaso-occlusive pain crises (VOCs). Hydroxyurea is a major therapeutic agent in adult and pediatric sickle cell patients. This treatment is an alternative to transfusion in some complications. Indeed, it increases hemoglobin F and has an action on the endothelial adhesion of red blood cells, leukocytes, and platelets. Although the safety profile of hydroxyurea (HU) in patients with sickle cell disease has been well established, the existing literature on HU exposure during pregnancy is limited and incomplete. Pregnancy in women with SCD has been identified as a high risk for the mother and fetus due to the increased incidence of maternal and non-fetal complications in various studies and reports. For women on hydroxyurea at the time of pregnancy, transfusion therapy should probably be initiated after pregnancy. In addition, there is still a significant lack of knowledge about the incidence of pregnancy, fetal and maternal outcomes, and management of pregnant women with SCD, making it difficult to advise women or clinicians on outcomes and best practices. Therefore, the objective of this study was to describe pregnancy outcomes (n = 128) reported in the noninterventional European Sickle Cell Disease COhoRT-HydroxyUrea (ES-CORT-HU) study. We believe that our results are important and relevant enough to be shared with the scientific community.

No difference in myocardial iron concentration and serum ferritin with deferasirox and deferiprone in pediatric patients with hemoglobinopathies: A systematic review and meta-analysis.

Iron overload is a common complication experienced by transfusion-dependent children with hemoglobin disorders. Chelators such as deferasirox (DFX) and deferiprone (DFP) are effective in overcoming this problem. We conducted this systematic review and meta-analysis to evaluate the effectiveness of DFX compared to DFP in treating iron overload amongst pediatric patients with hemoglobin disorders. PubMed and Cochrane Central were searched from their inception until Dec 21 2021, for randomized clinical trials (RCTs) and observational studies, which assessed the efficacy of DFX compared to DFP in the treatment of inherited hemoglobin disorders. The outcomes of interest included myocardial iron concentration (MRI T2*) at the end of the trial and change in mean serum ferritin (SF) levels at the 6 and 12months mark. Weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were calculated for continuous outcomes using random effects model. A total of 5 studies comprising 607 children were included. The results of our analysis revealed no significant difference between DFX and DFP in MRI T2* at the end of treatment (WMD: -0.92; 95% CI [-3.35, 1.52]; p=0.46; I2=0). Moreover, there has been no significant difference noted in SF levels at both 6months (WMD: 97.31; 95% CI [-236.16, 430.77]; p=0.57; I2=0) and 12months (WMD: 46.99; 95% CI [-191.42, 285.40]; p=0.70; I2=0) respectively. Our analysis shows no significant difference between the efficacy of DFX and DFP in the management of iron overload in children with inherited blood disorders. Future large-scale clinical trials are required to further validate our results.

Foetal haemoglobin inducers for reducing blood transfusion in non-transfusion-dependent beta-thalassaemias.

Foetal haemoglobin inducers for reducing blood transfusion in non-transfusion-dependent beta-thalassaemias.

Systematic Review of Metabolic and Endocrinological Complications in Beta-Thalassemia Major: Insights from 2021 to 2023

Beta-thalassemia major (BTM) is a recessively inherited hemoglobin disorder characterized by inadequate synthesis of the -globin chain, resulting in severe anemia necessitating frequent blood transfusions. Advances in transfusion and chelation therapies have substantially extended the life expectancy of BTM patients, enabling them to reach their fourth and fifth decades. This systematic review focuses on assessing the incidence of metabolic and endocrinologic complications among individuals with BTM in Saudi Arabia. The review covers studies published between 2021 and 2023, gathered from Google Scholar, Web of Science, Cochrane, and PubMed databases, utilizing keywords such as \&amp;quot;Metabolic,\&amp;quot; \&amp;quot;Endocrinologic,\&amp;quot; \&amp;quot;complications,\&amp;quot; \&amp;quot;beta-thalassemia,\&amp;quot; \&amp;quot;major,\&amp;quot; and \&amp;quot;Saudi Arabia\&amp;quot; in various combinations. Only original research discussing metabolic and endocrinologic complications in BTM was included, yielding nine eligible articles out of a total of 100. Among these, three were cross-sectional, two were descriptive, one was a case report, one was retrospective, and two were prospective analytical studies. The collective study population comprised 891 male and female BTM patients ranging in age from 2 to 35 years. This review reveals a notable prevalence of endocrine complications in BTM patients, with prominent occurrences of short stature, thyroid dysfunctions, growth hormone deficiency, and Diabetes mellitus. Additionally, other reported complications encompassed elevated serum ferritin levels, vitamin D deficiency, delayed puberty, microcytic hypochromic anemia, splenectomy, and heart failure. Remarkably, elevated serum ferritin levels exhibited a strong correlation with increased endocrine disorders, including serum TSH, fasting and postprandial blood glucose levels, and insulin levels in BTM patients.

The Effects of Vitamin D on Myocardial Function Demonstrated by Speckle-Tracking Echocardiography in Children with Beta Thalassemia.

Beta thalassemia major is an inherited hemoglobin disorder resulting in chronic hemolytic anemia. Cardiac involvement is the main cause of death in patients. Speckle-tracking echocardiography is a feasible method for the evaluation of cardiac function via an assessment of the longitudinal deformation of the myocardium through the cardiac cycle. The aim of our study is to evaluate the association between vitamin D deficiency and deformation of the left ventricular myocardium measured by speckle-tracking echocardiography in children with thalassemia major. In this prospective study, 33 thalassemic patients with vitamin D deficiency were enrolled. Cardiac magnetic resonance T2* value, conventional echocardiography, and speckle tracking, and also left ventricular longitudinal and circumferential strain values were measured. Myocardial functions of the patients with vitamin D deficiency or insufficiency were evaluated by speckle-tracking echocardiography before and after vitamin D replacement. The mean age of the patients was 15.4 ± 3.09 years. Vitamin D level was deficient in 30 (90%) and insufficient in 3 (10%) of them. Speckle-tracking analysis showed a significantly decreased absolute value of the left ventricular global longitudinal strain before vitamin D replacement. A significant improvement in the global longitudinal strain was detected after vitamin D replacement (P < 0.05). A statistically significant increase was observed in parameters showing left ventricular systolic and diastolic functions after vitamin D replacement. Vitamin D deficiency is frequently observed and causes decreased contractility in thalassemic patients. In our study, we observed that our patients' cardiac functions had improved after vitamin D replacement therapy.

Non-Invasive Optical Characterization of Tissue Hemodynamics in Sickle Cell Patients Undergoing Treatment with Isoquercetin

Sickle Cell Disease (SCD) is an inherited hemoglobin disorder which causes a mutation in the β subunit of hemoglobin (HbA), thus producing hemoglobin S (HbS) (Williams and Thein, 2018). When HbS is deoxygenated, red blood cells (RBC) can polymerize, which promotes increased rigidity and microvascular occlusions. The presence of mutated HbS increases the likelihood of recurrent venous thromboembolism (VTE). There is an unmet need for real-time, non-invasive methods of assessing microvascular hemodynamics and endothelial dysfunction. Near-Infrared Spectroscopy (NIRS), is a non-invasive, optical technique which measures tissue absorption and scattering between 650-1100 nm in subcutaneous tissue. NIRS has the capability to quantitatively measure the concentration of oxy- and deoxy- hemoglobin as well as blood flow. To determine the sensitivity of NIRS to changes in hemodynamics in SCD patients, we evaluated a cohort of SCD patients undergoing treatment with Isoquercetin (IQ), a flavonoid antithrombotic agent, and correlated the findings with D-dimer, a marker for blood clot degradation. We recruited a sub-cohort of 17 of 46 patients participating in a randomized, double-blind, placebo-controlled trial of IQ and performed an optical hemodynamic assessment at baseline and 4 weeks post-treatment. We used the commercial, multi-modal NIRS device (MetaOx, ISS Inc) which combines frequency-domain NIRS (FD-NIRS) and diffuse correlation spectroscopy (DCS) to acquire optical markers of tissue composition and blood flow, respectively. NIRS testing included resting baseline measurements and a brachial cuff occlusion. As seen in Figure 1A, a blood pressure cuff was wrapped around the bicep and the NIRS probe was placed on the ipsilateral forearm muscle. The challenge consisted of a 3-minute baseline, 3-minute cuff occlusion at 200 mmHg, and a 3-minute recovery. The decay constant τc of the intensity autocorrelation function g2(τ), which is an indicator of the bulk displacement of scattering particles (i.e. RBCs) in the forearm, was fitted from the DCS data. We compared the mean τc during the last 30s of the occlusion to D-dimer levels for all 17 patients at baseline and at 4 weeks follow up. Following a data quality review, 8 patients had NIRS data for baseline and follow up visits. D-dimer levels were 1.875 mcg/mL ± 0.869 mcg/mL at baseline and 1.449 mcg/mL ± 0.874 mcg/mL at 4 weeks follow up. Among the 8 patients with good quality data, 5/8 showed an average decrease in τc by 0.424 ms at 4 weeks follow up and an average decrease in D-dimer levels by 0.768 mcg/mL. The patient in Figure 1B showed 42.0% decrease in τc and 46.6% decrease in D-dimer levels from baseline to 4 weeks follow up. 2/8 patients showed an increase in τc by an average of 0.139 ms and an average increase in D-dimer levels by 0.320 mcg/mL. 1/8 patient showed a decrease in the τc with no change in D-dimer levels. We found that 7/8 patients with baseline and follow up visits had matching trends between D-dimer levels and τc. As demonstrated, a larger τc signified less movement of scattering particles, such as RBCs, due to increased blood coagulation. The remaining 9/17 patients had data from one visit of acceptable quality and were excluded from this analysis. The results of this initial analysis demonstrate autocorrelation decay time could be a promising metric that is reflective of blood coagulation and rheology. While this analysis focused on the changes observed in optical blood flow markers, further work will be performed to both expand upon this analysis and to integrate the compositional data acquired from the FD-NIRS portion of the measurements. NIRS can potentially complement traditional blood biomarkers when assessing anti-thrombotic effects of SCD treatments, such as Isoquercetin. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical Presentation of Hemoglobin C in Albania: Case Series

The presence of HbC is a rare event in Europe and Mediterranean region where thalassemia and HbS are more frequently encountered. The rarely diagnosed cases are linked with the migration from West-Central Africa. Albania is one of the Mediterranean countries where inherited haemoglobin disorders are considerably widespread. Studies have shown the presence of thalassemia, sickle cell disease and sporadic cases of Hb O-Arab, Hb Lepore especially in the areas where malaria has been endemic. In 2006 we identified the first case with HbSC disease and until 2020 we have found 15 cases with HbC variant.&#x0D; In this study we have collected and analyzed the laboratory and clinical data of HbC cases. Our data support reports that HbC combinations with HbS and beta thalassemia are clinically important. Our data confirm the presence of the HbC variant in ex-malaric areas where thalassemia and HbS are quite widespread.

Three Haemoglobin Variants for Congenital Erythrocytosis and Sickle Cell Disease HbSC

The inherited haemoglobin disorders and the clinical laboratory is essential in the diagnosis. Phlebotomy is the therapeutic procedure indicated to reduce blood viscosity and decreasing the risk of thrombotic events in the haemoglobin variants with high affinity for O2 or vaso-occlusive crises in Sickle Cell Disease (SCD) with double heterozygosity HbSC. We describe how therapeutic bleeding remains the treatment in two variant haemoglobinopathies, Haemoglobin Regina and the Haemoglobin Trollhattan, reported for the first time in the Italian population and a double heterozygosity HbSC. In patients with high haematocrit level when other secondary conditions of polyglobulia are excluded, a High-Performance Liquid Chromatography (HPLC) analysis for haemoglobin study should be suggested. Also in children with erythrocytosis frequently, such as the finding of Haemoglobin Okazaky.

Non-traumatic head swellings in a child with a sickle cell disease presented to a tertiary hospital North of Tanzania: A case report

Abstract&#x0D; Sickle cell is the commonest inherited haemoglobin disorder in Sub-Saharan Africa. Often patients present with painful crises in the extremities. But rarely non-traumatic Sub-galeal hematoma whose pathogenesis is not clearly defined, presenting with scalp swellings can occur. We present a case, nine years old male, with this uncommon complication which is also known as Acute Soft Head Syndrome and was managed conventionally at a tertiary hospital in Tanzania with hydration, analgesics, blood transfusion and antibiotics with marked improvement within a week.&#x0D; &#x0D;