Beta-thalassemia Patients Research Articles

Bone and Joint Involvement in Beta Thalassemic Patients: A Cross-sectional Study

Bone and Joint Involvement in Beta Thalassemic Patients: A Cross-sectional Study

Plasma sphingomyelin levels were negatively correlated with ferritin levels in splenectomized thalassemia patients

Abstract Beta thalassemia results from decreased production of beta chains due to either mutations or deletions in the beta-globin gene, leading to impaired production of hemoglobin A. Thalassemia patients take frequent blood transfusions to compensate for hemolytic anemia and iron overload. Iron overload is monitored by serum ferritin levels in these patients. Extra-medullary hematopoiesis in beta thalassemia major leads to hypersplenism which often necessitates splenectomy to increase red cell life span and decrease transfusion need. Sphingomyelin is the second most abundant phospholipid in human plasma after phosphatidylcholine. In contrast to the well-defined roles of sphingolipids in cell membranes, their possible physiological role in lipoprotein metabolism has recently gained attention. Increased circulating levels of sphingomyelins and ceramides were observed in obesity, diabetes, and cardiovascular diseases. Although lipid abnormalities such as hypocholesterolemia and relatively increased triglycerides were reported in beta-thalassemia patients, there is no study investigating sphingolipid levels in thalassemia. Therefore, we investigate certain long chain and very long chain sphingomyelins and ceramides in beta-thalassemia patients who are under routine follow-up in our hospital. Thalassemia major patients who applied to the hospital for regular blood transfusion and gave consent were included in the study. Blood samples were obtained before transfusion. Plasma sphingomyelin (C16, C18 and C24) and ceramide (C16, C18, C20, C22, C24) species were measured by triple quadruple LC-ESI-MS/MS (Shimadzu, Japan). D-erythrosphingosine-D9 (Matreya) was used as an internal standard, all other lipid standards were from Avanti. Body iron stores of the patients were monitored by serum ferritin levels. A total of thirty patients were included in the study. All patients typically received regular erythrocyte suspension transfusions every three weeks and continuous oral iron chelation therapy. Twenty of the patients had a previous splenectomy. The mean age was 34.5 ±8.1 years in the splenectomy group and 32.8 ±8 years in the group without splenectomy. Mean ferritin levels were not different between the groups, being 1073.2±563.5 µg/L in splenectomy and 1709 ±1660.4 µg/L in non-splenectomy groups. All measured sphingolipid levels were similar between splenectomy and non-splenectomy groups. When correlation analysis was performed between measured sphingolipid and ferritin levels, significant negative correlations were found between sphingomyelin C16 (r= -0.591 p<0.006) and C18 (r= -0.594 p<0.006) with ferritin levels in the splenectomy group. However, this negative correlation was absent in the non-splenectomy group. In conclusion, we found that iron overload is associated with lower plasma sphingomyelin levels in splenectomized thalassemia patients. We have been working on the lipidomic analysis of the plasma and erythrocytes of thalassemia patients and other hemolytic anemias. The results may further help to get a better picture of lipid metabolism in thalassemia.

Transfusion burden and willingness to pay for temporary alleviation of anemia status in transfusion-dependent beta-thalassemia patients in China

BackgroundTransfusion-dependent β-thalassemia (TDT) is one of the global public health concerns highlighted by the World Health Organization. Patients with TDT require regular blood transfusion to survive. However, the availability of blood resources is extremely limited. The purpose of this study was to investigate transfusion burden and willingness to pay (WTP) for temporary remission of anemia status among patients with TDT and to explore the associated factors.MethodsAdult patients with TDT were recruited through cluster sampling across several high-incidence provinces in China. Consenting patients completed online questionnaires on demographic information, transfusion burden and WTP with real-time WeChat communication assistance from researchers. The guiding techniques of double-bounded dichotomous choices and open-ended questions in the contingent valuation method (CVM) were used to obtain participants’ WTP for 1 unit of leukocyte-depleted red blood cells. WTP calculations were performed using maximum likelihood estimation, with further insights gained through subgroup analysis based on gender, family monthly income level and convenience of blood transfusion.ResultsThe analysis included 149 TDT patients from five high-incidence provinces, with an average monthly income of $198.5. Patients received an average of 3.7 units per transfusion, 15.4 times annually, with an average WTP of $70.4 per unit (95% CI [62.0, 78.9]). Estimated WTP for temporary anemia alleviation per transfusion totaled $260.6, exceeding monthly income by 1.32 times. Higher WTP was observed among males, higher-income households, and those with at least junior education. Lower WTP was noted among patients with lower transfusion volumes and those needing to travel for transfusion or during hospitalization for blood transfusion.ConclusionHigh WTP indicated a strong desire for temporary anemia relief. Most TDT patients faced significant economic and transfusion burden. The evident gap in meeting clinical needed underscores the urgent demand for innovative treatments to reduce transfusion dependency, potentially transforming TDT care and improving socioeconomic well-being and clinical outcomes. These findings supported evidence-based decision-making for TDT pharmacoeconomics and efficient healthcare resource allocation in China.

IRON OVER LOAD AND ITS RELATION WITH HAEMOSTATIC PARAMETERS IN BETA-THALASSEMIA PATIENTS

Background: Patients with beta-thalassemia major have been observed to experience changes in their coagulation profile. These changes include an elongated prothrombin time and partial thromboplastin time as well as bring down levels of natural anticoagulants and coagulation factors. The mechanisms underlying the occurrence of thrombotic tendencies in some thalassemia patients remain unclear. This study aims to examine the alterations in the iron and coagulation profile among beta-thalassemia patients. Methods: After informed consent, 50 children having beta-thalassemia, and 50 healthy controls were included in this study. Blood samples were collected and serum ferritin, haematological and haemostatic parameters were measured. Data was analysed on SPSS-24. Results: The laboratory assessment revealed 43.5% of the patients had thrombocytopenia, 54% had prolonged prothrombin time (PT), and 56% of the patients had prolonged activated partial thromboplastin time (aPTT). All estimated coagulation factors exhibited lower activity levels in comparison to the control group. Serum ferritin exhibited a positive relationship with PT and aPTT and a substantial negative relationship with total platelet count. Conclusion: High serum ferritin levels are associated to abnormal haemostatic parameters in thalassemia patients. Regular monitoring of serum ferritin levels is essential to ensure that thalassemia patients receive appropriate treatment and support. Pak J Physiol 2024;20(3):71–3, DOI: https://doi.org/10.69656/pjp.v20i3.1742

Vitamin D Deficiency among Blood Transfusion-Dependent Beta Thalassemia Children Admitted to Tertiary Level Pediatric Hospital in Nepal: A Descriptive Cross-Sectional Study

Introduction: Children with beta thalassemia are on regular blood transfusions, which could result in iron deposition in the liver causing decreased synthesis of Vitamin D-25OH. There are limited publications on the association of Vitamin D deficiency with blood transfusion-dependent thalassemia in the Nepalese population. This study aims to determine the prevalence of Vitamin D deficiency among blood transfusion-dependent beta-thalassemia patients.Methods: This was a descriptive cross-sectional study conducted among beta-thalassemia major patients under 15 years of age, receiving regular blood transfusion, from July 17, 2022, to July 16, 2023, after ethical approval obtained from Ethical Review Committee, Kanti Children’s Hospital (reference number 155). Data were collected using convenience sampling, and descriptive analyses were performed using Microsoft Excel and Statistical Package for Social Sciences (SPSS) 2024.Results: A total of 127 blood transfusion-dependent beta-thalassemia major patients were included in the study, of whom 82 (64.56%) were male. Among these patients, 104 (81.88%) were aged between 5 and 14 year. Almost one-third 41 (32.28%) had Vitamin D insufficiency, and a quarter, 34 (26.77%), had Vitamin D deficiency. Ten percent of the children were underweight, and a quarter were stunted.Conclusions: Children with blood transfusion dependent beta thalassemia major are at a greater risk for Vitamin D deficiency and iron overload

Assessment of Serum Autophagy Related Protein Beclin-1 in Egyptian Adult Beta Thalassemia Patients

Assessment of Serum Autophagy Related Protein Beclin-1 in Egyptian Adult Beta Thalassemia Patients

Comparison of Efficacy and Safety of Thalidomide vs Hydroxyurea in Thalassemia Patients: A Single-Centre Pilot Study

Abstract: Background: Beta thalassemia is a genetic disorder causing defective beta globin chain formation, leading to ineffective erythro- poiesis and hemolysis. It has three types: thalassemia major, thalassemia intermedia, and thalassemia minor. Treatment options include blood transfusions, iron chelation therapy, and bone marrow transplantation, but new treatments like HbF inducers (e.g., hydroxyurea) and erythro- poiesis modulators are being developed. Thalidomide and hydroxyurea are also being used to manage thalassemia by increasing HbF synthesis and reducing transfusion frequency. Objective: To compare the efficacy and safety of thalidomide and hydroxyurea in beta-thalassemia patients for a period of six months. Materials and Methods: A Prospective interventional single-centre study was conducted the tertiary care hospital of southern Pakistan, from 1st September 2021 to 03rd March 2022. A total of 39 patients of beta thalassemia major and intermediate with age ranges of >10 and <30 years were enrolled in this study. 24 patients were fulfilling the study requirement. Thalidomide was started with a dose of 50 mg/day (in patients >10-13 years) while the adult dose was 100 mg /day (age >13 Years) every night. Hydroxyurea was given at 15 mg/kg /day. Pre and post-treat- ment tests were done. For assessing the safety of thalidomide and hydroxyurea biochemistry test was done along with LDH, Platelets counts, and WBCs count. The efficiency of both drugs was analyzed by hemoglobin, reticulocyte count, nucleated red blood cells, MCV, MCHC, white blood cells, and platelets. Result: Both groups showed a highly significant increment in Hb. Thalidomide treated group baseline was 6.8 ±1.3 and after 06 months 8 ±13; (p-value <0.001). Furthermore reticulocyte count was highly significantly augmented in HU treated group (p-value <0.001) Hydroxy- urea-treated group showed significant decline in NRBC with a difference of -2.3±1.1 (p-value 0.02). Moreover, the transfusion interval was more significantly increased in the thalidomide group. The hemolysis parameter, LDH significantly declined in both groups. The hydroxy- urea-treated group showed difference of -62.4±124.4 (p-value 0.03) while the thalidomide-treated group showed a difference of -64.36±32.9 (p-value 0.05). AST was only significantly decreased in thalidomide treated group. Conclusion: Among both groups, hemoglobin, RBCs and reticulocyte count levels raise in both groups while NRBCs significantly decrease in HU treated group. Moreover, transfusion interval was also significantly increased by thalidomide. It shows safety by significantly decreasing the TBIL and AST, whereas LDH was decreased in the HU-treated group. This clinical trial was registered as # NCT06239389.

Effectiveness of topical 25% silver nitrate solution followed by 5% fluoride varnish compared to 38% silver diamine fluoride in arresting and preventing dental caries among beta-thalassemia major patients: A randomized clinical trial

IntroductionThis is the first randomized non-inferiority clinical trial in the evidence literature to examine the effectiveness of topical 25% silver nitrate (SN) followed by 5% sodium fluoride (NaF) varnish is not much worse or acceptable to 38% silver diamine fluoride (SDF) in preventing and arresting dental caries among Beta-Thalassemia Major (BTM) patients. Method170 BTM participants aged 18 years and older with at least 1 or more active carious lesions were randomly allocated into 2 groups (1:1). 25% silver nitrate solution application followed by 5% NaF varnish was administered to Group I, and Group II received 38% SDF. The Nyvad criteria and DMFT index were used to assess caries arrest and prevention among both groups at 3- and 6-months interval. ResultsCaries arrest rate at 3 months was significantly higher in Group I (83.10%) when compared to Group II (76.16%) (p<0.05). While at 6 months, both the groups were comparable with arrest rate (76.16%) (p>0.05). The caries increment was comparable among both groups at 3 months, while at 6 months, caries increment was almost half in SN with NaF group compared to SDF group (p>0.05). Kaplan–Meir survival estimated the median survival time for caries increment was 17 and 39 weeks for Group I and 15 and 36 weeks for Group II at 3 and 6 months, respectively. ConclusionOne time application of 25% SN followed by 5% NaF is no worse than a 38% SDF in arresting and preventing dental caries among Thalassemia Major participants at 3 and 6 months. Clinical SignificanceThe study provides clinicians with a cost-effective, safer, readily available, non-invasive treatment option (25% SN followed by 5% NaF) for caries management.

Assessment of the vitamin D level and demographic characteristics of children suffering from β-thalassemia in Thi-Qar province

Beta thalassemia is a genetic disorder inherited by autosomal recessive inheritance, is present all over the world . Lifelong transfusions are necessary for people with beta-thalassemia, which can result in an iron buildup in the skin, liver, and kidneys that reduces the production of vitamin D. This study aims to evaluate vitamin D levels, blood groups, and demographic characteristics in beta-thalassemia patients. The current study was conducted at the thalassemia center and hereditary blood disease in Thi-Qar Province with eighty-eight blood samples collected from individuals. It was divided into three groups according to age range, the first group (2-6), the second group (7- 11), and the third group (12- 15). In the current study, there was a significant decrease in Vit-D3 levels among thalassemia patients compared to the control group (p ≤ 0.05) . As for age between the patients group and the control group, the highest proportion of patients in the third age group. As for gender, the results of the study found a non-significant difference at the (P ≤ 0.05 ) level between the patients group and the control group. The most common blood group in thalassemia was O followed by blood groups A, B, and AB. It also shows that the majority of the population was positive Rh.

Clinico-Laboratory Profile of Hypertriglyceridemia Thalassemia Syndrome: A Case Series in a Paediatric Tertiary Care Centre.

Increased hemolysis and repeated blood transfusion trigger oxidative stress resulting in numerous adverse effects in beta-thalassemia patients. Extreme elevation of triglyceride level is a rare clinical entity seen in these patients. It is presumed to be caused due to an increase in oxidative stress and is termed Hypertriglyceridemia Thalassemia Syndrome. To assess the clinical and laboratory characteristics of beta-thalassemia patients presenting with hypertriglyceridemia and its correlation with the pre-transfusion hemoglobin level. Methods: This hospital record-based retrospective study was conducted at the Dr B C Roy Post Graduate Institute of Paediatric Sciences, Kolkata, India. The study comprised 12 pediatric beta-thalassemia patients whose plasma appeared milky or chylous during a complete hemogram. Clinical examination and laboratory investigations were done to describe their clinico-laboratory features. A whole exome sequencing was carried out to assess their genetic background. Blood hemoglobin and serum triglyceride estimation was carried out initially and at follow-up to determine any correlation between the two. Results: Out of 1482 patients, 12 (0.80 %) were diagnosed with Hypertriglyceridemia Thalassemia Syndrome. The median age of presentation was 12.5 months (Q1:10 months, Q3:14 months)., and the pretransfusion hemoglobin was 4.82 ± 1.16 g/dL. The lipid profile showed a triglyceride level of 858.3 ± 198.4 mg/dl and a total cholesterol level of 117.4± 16.15 mg/dl. Analysis revealed that the triglyceride levels were negatively correlated with the pretransfusion hemoglobin level (repeated measures correlation (rmcorr) = -0.65, 95% CI[-0.794, -0.425], p < 0.001). A genetic study highlighted c.92+5G>C as the commonest mutation. Hypertriglyceridemia was a rare presentation in transfusion-dependent beta-thalassemia patients. The serum triglyceride level significantly reduced when blood transfusion at regular intervals restored the patient's hemoglobin level.

An Investigation of Group-Based Mobile Learning on Stress, Anxiety, Depression, and Pain Among Beta-Thalassemia Major Patients: A Randomized Control Trial.

Beta-thalassemia major (B-TM) is an inherited hematological disease that affects nearly 300 million people worldwide. This study aimed to evaluate the effects of group-based mobile learning on stress, anxiety, depression, and pain among beta-thalassemia major patients. This randomized clinical study was conducted on 48 patients with beta-thalassemia major in Jahrom, Iran. Participants were randomly assigned to the control and intervention groups. Their partners in the intervention group were trained in self-care through mobile learning. The 21-item Depression, Anxiety, and Stress Scale and a visual analog scale for pain assessment were used to collect the data. Data were analyzed using the Statistical package for the Social Sciences version 23.0. Although there was no significant difference between the control and intervention groups in the mean pre-test scores of depression (P = .21), anxiety (P = .05), stress (P = .48), and pain (P = .46), the mean post-test scores of depression, anxiety, and stress in the intervention group were significantly lower than the control group (P = .0001). The mean scores of depression (P = .33), anxiety (P = .74), stress (P = .83), and pain (P = .6) did not change significantly in the control group, while all these mean scores decreased significantly in the intervention group for DASS (P = .001) and pain (P = .002). Group-based mobile learning is effective in reducing depression, anxiety, stress, and pain in B-TM.

Effectiveness of an Educational Program on Improving Nursing Care for Thalassemia Patients Undergoing Blood Transfusion

Background: Thalassemia is a genetic disorder that disrupts hemoglobin production, leading to severe anemia. Beta-thalassemia major patients often require lifelong blood transfusions. Nurses play a crucial role in managing these transfusions, but gaps in knowledge and practice can lead to complications. This study assessed the impact of an educational program on nurses' knowledge and skills regarding thalassemia and blood transfusion protocols. Methods: A quasi-experimental study was conducted at the Jin Pediatric Hematology-Oncology Center in Duhok City, Iraqi Kurdistan. The sample included 20 nurses. The program consisted of four sessions (two theoretical and two practical). Data collection instruments included a socio-demographic sheet, a knowledge questionnaire, and a skills checklist. Pre- and post-intervention knowledge and practice scores were analyzed using paired t-tests and chi-square tests. Results: The educational program significantly improved nurses' knowledge of thalassemia (P &lt; 0.00) and transfusion protocols, with the mean knowledge score increasing from 5.2 ± 2.09 to 8.05 ± 1.82. Practice scores also showed statistically significant improvements (P &lt; 0.002). Correlations between total knowledge and practice scores, as well as with nurses' experience and educational level, were statistically significant. Conclusion: The study demonstrated that an educational program can enhance nurses' knowledge and practices in managing thalassemia patients undergoing blood transfusions. Continued education and targeted interventions are essential to improving the quality of care for these patients.

Mandibular analysis of Beta thalassemia patients from hematological institutes of Karachi Pakistan.

Objective: To study the mandibular changes in the β-thalassemia major patient. Study Design: Cross sectional study. Setting: Husaini Blood Bank and Institute of Hematological Diseases Karachi, Department of Oral and Maxillofacial Surgery, and Department of Orthodontics, Baqai Dental College Baqai Medical University, Karachi. Period: January 2023-December 2023. Methods: 50 Orthopanthogram (OPG) radiographs of beta-thalassemia major patient were taken, analyzed and compared to check any variation from normal. Fifty diagnosed β-thalassemia major patients were voluntarily selected through convenience sampling. The study was carried out in collaboration of Husaini Institute of Blood Diseases Karachi, National institute of Oral Diseases Karachi Pakistan and, Department of Oral and Maxillofacial Surgery and department of orthodontics Baqai Dental College Baqai Medical University. Results: 18 (36%) patient’s alteration of trabecular pattern are present and in 32 (64%) patient alteration of trabecular pattern absent. Similarly, in 16 (32%) patients have short spiky roots are present and 34 (68%) patients short spiky roots absent. Conclusion: Effect of anemia is not so profound in mandible of thalassemia patients from population of Karachi.

Mutation Analysis of Exon 1 in the Hemoglobin Subunit Beta (HBB) Gene in Beta-Thalassemia.

Introduction Thalassemia is a widely prevalent monogenic hematological disorder found worldwide. It exists in two forms: alpha- and beta-thalassemia. Alterations in the hemoglobin subunit beta (HBB) gene cause beta-thalassemia, with missense and point mutations affecting beta-globin synthesis. Consequently, genetic screening for beta-thalassemia is essential for genetic counseling, carrier screening, and prenatal diagnosis. Aim and objective This study aims to examine and identify mutations in the exon 1 region of the HBB gene in beta-thalassemia patients from the Vijayapura region. Methods This study involved 47 clinically diagnosed children with beta-thalassemia from a hospital in Vijayapura, India. Detailed clinical histories of all patients were recorded. Genomic DNA was extracted from the blood samples of these patients and subjected to polymerase chain reaction (PCR) using exon-specific primers for the HBB gene. The PCR products were then sequenced using the capillary-based Sanger sequencing method to identify mutations in the HBB gene. Results A total of 47 clinically diagnosed beta-thalassemia patients were included in the study, comprising 30 males and 17 females, aged between one and 20 years. Sequencing analysis of exon 1 in the beta-globin gene identified 17 beta-thalassemia variants. The most common mutation observed was T>G, G>C, C>A, and C>T in the exon 1 region of the HBB gene. Conclusion This study identifies the pattern of beta-thalassemia mutations, aiding in the prevention of the disorder through prenatal diagnosis and genetic counseling. Mutations can alter codon sequences, affecting protein production. Research highlights the importance of a primary prevention program to analyze mutations and sequence variations at the molecular level, thereby helping to address numerous genetic disorders.

Correlation between plasma biochemical parameters and cardio-hepatic iron deposition in thalassemia major patients

Introduction Major Thalassemia patients suffer from iron overload and organ damage, especially heart and liver damage. Early diagnosis and treatment with a chelator can reduce the complications and mortality of iron overload. Therefore, we aimed to investigate the biochemical and hematological predictors as an alternative and indirect indicator of iron deposition in heart and liver cells in comparison with the MRI T2* method as the gold standard. Material and method MRI T2* was evaluated in the heart and liver tissues of 62 major beta-thalassemia patients undergoing regular transfusion and chelator therapy. Biochemical and hematological factors were also measured, including serum ferritin, serum electrolytes, liver enzymes, hemoglobin, blood glucose, and serum magnesium. The correlation between these factors was assessed using statistical evaluations. Result Serum ferritin had a positive and significant correlation with liver siderosis based on MRI T2* (p-value = .015), and no significant association was observed with cardiac siderosis (p-value = .79). However, there was a significant positive correlation between cardiac iron deposition and fasting blood sugar level (p-value = −.049), and plasma level of liver enzymes (alanine aminotransferase (ALT) (p-value = .001), aspartate aminotransferase (AST ((p-value = .01)). Moreover, there was a significant negative correlation between cardiac iron overload and plasma magnesium level (p-value = .014). According to MRI T2*, there was no significant correlation between cardiac and hepatic iron overload (p value = .36). Conclusion An increase in blood sugar or liver enzymes and a decrease in serum magnesium was associated with an increase in cardiac iron overload based on MRI T2*. Liver iron overload based on MRI T2* had a significant correlation with serum ferritin.

An unusual co existence of Hematological malignancy and Avascular Necrosis in previously diagnosed young HB E beta Thalassemia patient

An unusual co existence of Hematological malignancy and Avascular Necrosis in previously diagnosed young HB E beta Thalassemia patient

Splenectomy in Thalassemia: The Role of Surgery as an Adjunct to Medical Management.

Introduction Beta thalassemia is a hemoglobinopathy characterized by defective production of the beta chain of hemoglobin, leading to irreversible destruction of RBCs, splenomegaly, pancytopenia, and a requirement for multiple transfusions. This condition necessitates iron chelation therapy, and splenectomy is often performed to manage hypersplenism. Methods This report includes a series of seven diagnosed cases of beta thalassemia with hypersplenism, all of whom underwent open splenectomy. Preoperative transfusions were administered to achieve target hemoglobin and platelet counts of 9 g/dL and 50,000/µL, respectively. Results The study included seven patients diagnosed with beta thalassemia, all of whom underwent open splenectomy. Among these, three patients also had concomitant cholecystectomy due to the presence of gallstones. The primary indication for performing splenectomy was hypersplenism. Preoperative transfusions were administered to ensure target hemoglobin levels of 9 g/dL and platelet counts of 50,000/µL. All patients were successfully discharged with minimal morbidity and no reported mortality. The longest follow-up period observed in this series was 10 months post-splenectomy, which limited the assessment of long-term effects. Conclusion Open splenectomy for hypersplenism in patients with beta thalassemia appears to be a safe and effective procedure with minimal short-term morbidity and no mortality observed in this series. However, due to the limited follow-up duration, the long-term effects of splenectomy in these patients could not be evaluated. Further studies with longer follow-up are needed to assess the long-term outcomes of splenectomy in beta thalassemia patients.

The search for pyruvate kinase-R activators; from a HTS screening hit via an impurity to the discovery of a lead series

Pyruvate kinase (PK) is an essential component of cellular metabolism, converting ADP and phosphoenolpyruvate (PEP) to pyruvate in the final step of glycolysis. Of the four unique isoforms of pyruvate kinase, R (PKR) is expressed exclusively in red blood cells and is a tetrameric enzyme that depends on fructose-1,6-bisphosphate (FBP) for activation. PKR deficiency leads to hemolysis of red blood cells resulting in anemia. Activation of PKR in both sickle cell disease and beta-thalassemia patients could lead to improved red blood cell fitness and survival.The discovery of a novel series of substituted urea PKR activators, via the serendipitous identification and diligent characterization of a minor impurity in an High Throughput Screening (HTS) hit will be discussed.

Importance of CD71+ Erythrocyte Cell Levels in Prognosis in Patients With β-Thalassemia.

CD71+ erythroid cells (CECs) are immature red blood cells (proerythroblasts, erythroblasts, and reticulocytes). CECs play an important role in the development of sepsis and cancer by causing immunosuppression. We examined the CEC levels in the peripheral blood of beta thalassemia (βThal) patients and investigated the relationship between CECs and the clinical status of the patients, especially splenectomy. Sixty-eight patients with βThal (46 splenectomized and 22 nonsplenectomized) and 15 healthy controls were included in this study. The hemogram parameters, ferritin, and CECs (flow cytometry method) were measured. It was observed that the CEC level in the patient group was significantly higher than the control group (p < 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy (p < 0.05). CEC levels were higher in patients with nontransfusion-dependent βT (NTD-βThal) than in patients with transfusion-dependent βT (TD-βThal) (p < 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy in both TD-βThal and NTD-βThal groups (p < 0.05). There was a moderate-negative correlation was detected between CECs and Hb levels (r = -0.467; p < 0.05). High CEC levels in βThal patients develop as a result of ineffective erythropoiesis. We think that keeping CEC levels under control is important for prognosis, especially in patients with splenectomy.

Brain perfusion changes in beta-thalassemia

BackgroundBrain injury in hereditary hemoglobinopathies is commonly attributed to anemia-related relative hypoperfusion in terms of impaired oxygen blood supply. Supratentorial and infratentorial vascular watershed regions seem to be especially vulnerable, but data are very scarce.AimsWe investigated a large beta-thalassemia sample with arterial spin labeling in order to characterize regional perfusion changes and their correlation with phenotype and anemia severity.MethodsWe performed a multicenter single-scanner cross-sectional 3T-MRI study analyzing non-invasively the brain perfusion in 54 transfusion-dependent thalassemia (TDT), 23 non-transfusion-dependent thalassemia (NTDT) patients and 56 Healthy Controls (HC). Age, hemoglobin levels, and cognitive functioning were recorded.ResultsBoth TDT and NTDT patients showed globally increased brain perfusion values compared to healthy controls, while no difference was found between patient subgroups. Using age and sex as covariates and scaling the perfusion maps for the global cerebral blood flow, beta-thalassemia patients showed relative hyperperfusion in supratentorial/infratentorial watershed regions. Perfusion changes correlated with hemoglobin levels (p = 0.013) and were not observed in the less severely anemic patients (hemoglobin level > 9.5 g/dL). In the hyperperfused regions, white matter density was significantly decreased (p = 0.0003) in both patient subgroups vs. HC. In NTDT, white matter density changes correlated inversely with full-scale Intelligence Quotient (p = 0.007) while in TDT no correlation was found.ConclusionRelative hyperperfusion of watershed territories represents a hemodynamic hallmark of beta-thalassemia anemia challenging previous hypotheses of brain injury in hereditary anemias. A careful management of anemia severity might be crucial for preventing structural white matter changes and subsequent long-term cognitive impairment.