Research status of ocular changes in beta-thalassemia major / 国际眼科杂志(Guoji Yanke Zazhi)

Beta-thalassemia major(β-TM)is an inherited disease caused by a defect in the synthesis of globin. The disease requires long-term blood transfusion and iron chelator treatment, which can cause various secondary changes in the body and eye tissues. Compared with normal peers, β-TM patients will show changes in the eye such as steeper corneal curvature, shallower anterior chamber, increased lens thickness, shorter axial length, and reduced tear secretion. At the same time, nutritional deficiencies and the use of iron chelator drugs will increase the risk of complicated cataract and retinal degeneration, thus affecting the quality of life of β-TM patients.This article combines relevant domestic and foreign literatures to explore and review the changes in the eye of β-TM patients, with a view to providing valuable insights for clinical practice.

Prevalence of hypogonadism in transfusion-dependent ß-thalassemia patients of Bangladesh: investigating the role of serum ferritin level as a diagnostic tool

ABSTRACT Introduction: Hypogonadism is one of the most frequent complications in transfusion-dependent thalassemia patients and early recognition and treatment is the core element in restoring impaired gonadal function. Despite the high burden of disease, relevant studies are scarcely addressing the gonadal function of such patients in Bangladesh. The pattern of gonadal function in transfusion-dependent thalassemia patients must be characterized before planning a generalized management plan. Moreover, since iron overload is a key reason behind hypogonadism in thalassemia patients, investigating the role of serum ferritin level as a diagnostic tool for hypongadism was also an aim of this study. Methods: This cross-sectional study was conducted at the Department of Transfusion Medicine of the Bangabandhu Sheikh Mujib Medical University. According to the inclusion and exclusion criteria, a total of 94 patients were enrolled in this study. A detailed history and thorough clinical examination were carried out in each patient and recorded using a pretested structured questionnaire. In addition, the laboratory assessment of serum ferritin, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol in serum were also performed. The data were analyzed using the STATA (v.16). Results: The mean age of the patients with transfusion-dependent thalassemia was 18.81 ± 4.65 (SD), with 53.3% of the patients being male. The overall prevalence of hypogonadism was 35.11%, 18.1% being normogonadotropic, 11.7% being hypogonadotropic and 5.3% being hypergonadotropic. The serum ferritin level was significantly higher (p < 0.001) in patients with hypogonadism (Eugonadal: 2,174.79 (± 749.12) ng/ml; Hypogonadal: 3,572.59 (± 1,199.49) ng/ml). The area under the receiver operating characteristic (ROC) curve of serum ferritin was high (0.83) and the p-value was highly significant (< 0.001). Conclusion: Therefore, the serum ferritin level and gonadal hormone analysis of transfusion-dependent thalassemia patients can be considered a screening tool for assessing gonadal function and early detection and prevention of hypogonadism.

Clinical study of unrelated mismatched hematopoietic stem cell transplantation for β-thalassemia major / 中华器官移植杂志

Objective:To explore the efficacy and safety of unrelated mismatched hematopoietic stem cell transplantation(HSCT)for thalassemia major.Methods:For this retrospective cohort study, 15 patients with β-thalassemia major underwent unrelated mismatched HSCT between January 2018 and April 2022. There were 8 males and 7 females with a median age of 7(3-12)years and a median ferritin level of 3 417.3(223-14 485)μg/L. The conditioning regimens on the basis of fludarabine(Flu), busulfan(Bu)and cyclophosphamide(CTX)and GVHD prophylaxis on the basis of cyclosporine(CsA), mycophenolate mofetil(MMF), anti-human thymocyte immunoglobulin(ATG)plus low-dose post-cyclophosphamide(PTCy)and mesenchymal stem cells were offered.Results:Up until April 1, 2022, 15 children were successfully implanted during a median follow-up period of 24.1(11-49)months and all of them achieved stable donor chimerism. The median time to neutrophil and platelet engraftment were 12(11-22)and 14(8-38)days respectively. Except for 2 deaths, 13 cases survived. The estimated 2-year probability of overall survival(OS)and thalassemia-free survival(TFS)were both 86.67%. There were 5 cases of acute graft versus host disease (aGVHD) below grade Ⅱ, 2 cases of grade Ⅲ to Ⅳ aGVHD, and 3 cases of localized chronic graft versus host disease (cGVHD) after transplantation. No gengralized cGVHD occurred. Both cytomegalovirus and Epstein-Barr virus were activated in five recipients.Conclusions:Unrelated mismatched donor HSCT is both safe and feasible for thalassemia major.

Comparative metavirome analysis in polytransfused patients

Due to the high transfusion volume, polytransfused patients with sickle cell disease (SCD) and beta-thalassemia are constantly exposed to parenterally transmitted infections. Currently, we have little information about the virome of such patients and how the virological composition might be influenced by the hemotherapy procedures that these patients receive. The objective of this study was to compare the viral diversity between these two groups with respect to the viral abundance and how it might be affected by the specific conditions of these groups. We sequenced by next-generation sequencing (NGS) and compared the virome of 30 patients with beta-thalassemia major, 45 with SCD, and 16 blood donors from the Blood Center of Ribeirão Preto, Brazil. Predominantly, commensal viruses including Torque teno virus (TTV) genotypes and human pegiviris-1 (HPgV-1) were identified in each group. Strikingly, while HPgV-1 reads were dominant in the SCD group, thalassemic patients showed high TTV abundance, expressed both in viral reads and genotypes. We speculated that the commensal virome of polytransfused patients might be influenced by the transfusion frequency and disease characteristics and that commensal viruses might be used as important genetic biomarkers for these hematological disturbances. Nevertheless, more specific studies are necessary to confirm a relationship between blood virome and transfusion treatment.

P-Wave and QT Dispersion in Children With βeta-Thalassemia

Aim:This study aimed atassessingP-wave and QT interval dispersion in children with β-thalassemia and to correlate them with various laboratory and echocardiographic data. Methodology:Subjects comprised of 30 children with β-thalassemia major as the patient group. 30 healthy children matched for age and sex served as the control group. All patients were evaluated clinically as well as by echocardiography and 12 leads ECG. The type of study isprospective case control study.Results:There was a statistically significant increase ofInterventricular Septal end diastole(IVSd),Interventricular Septal end systole(IVSs),Left Ventricular Internal Diameter end diastole (LVIDd), Left Ventricular Internal Diameter end systole(LVIDs) andLeft Ventricular Posterior Wall end diastole(LVPWd) in patients as compared to controls (Mean ±SD = 0.950±0.166, 0.863±0.103, 3.983±0.456, 2.947±0.535and 0.797±0.165 respectively) (P < 0.05). Moreover, there were a significant increase of LV mass (Mean ±SD = 107.267±26.736, P= 0.002) and LV mass index of the studied patients (Mean ±SD = 106.900±22.651, P = 0.005)compared to the controls. There were significant decrease ofejection fraction(EF%)(Mean ±SD = 60.373 ± 8.088, P = 0.032)and fractional shortening(FS%) (Mean ±SD = 29.495 ± 4.171, P = 0.026) of the studied patients compared to control group. Both P wave dispersion (PWd) (Mean ±SD = 33.667 ± 13.767, P = 0.029) and QT dispersion (QTd) (Mean ±SD = 53.000 ± 18.411, P = 0.001) were significantly higher in patients compared to controls. There was a significant positive correlation between PWd and serum ferritin(r =0.551,P-value=0.002), LVIDd (r =0.406,P-value=0.026), LVPWd(r =0.461,P-value=0.010), LV mass (r =0.412,P-value=0.024), and LV mass index(r = 0.379,P-value=0.039). While, there were a significant positive correlations between QTd and serum ferritin (r =0.654,P-value <0.001), LVIDd (r = 0.388,P-value =0.034), LV mass (r = 0.454,P-value =0.012)and LV mass index (r = 0.456,P-value =0.011). Conclusion:P wave dispersion and QT dispersion were prolonged in children with β-thalassemia major denoting cardiac autonomic dysfunction with homogeneity disorders of atrial conduction and ventricular repolarization in these patients

Study of Ocular Manifestations among Beta Thalassemia Major Patients

Person with thalassemia major may have severe symptoms and may need regular blood transfusions. Iron overload is due to repeated blood transfusions and enhanced iron absorption by gastrointestinal tract and also creates negative impact on the organs function. We aimed to study the ocular changes in beta thalassemia major at a tertiary care hospital. Methods: In this prospective observational study, 234 patients diagnosed with beta thalassemia major, receiving multiple blood transfusions as a part of treatment were included. Patient brief history was taken, along with family history. Complete eye examination done. Ocular examination done by measuring visual acuity, refractive error assessment with autorefractometer, slit lamp examination, fundoscopy, perimetry, tonometry, color vision testing and tear break up time (TBUT) test. Results: A total of 234 beta thalassemia major patients of both sexes were evaluated, among them 132 (56.4%) were males and 102 (43.5%)were females. The mean age of thalassemic study population was 25.6±6.3. Most commonly observed were pinguecula (44%), visual field defects (40.5%), vascular tortuosity (39.3%), dry eye (33.3%), Refractive error (20.5%), Anterior segment involvement (18.8%), Cataract (13.2%), color vision defect (5.1%), normalization of optical vessels (4%). Conclusion: Regular Opthalmological examination helps to detect early changes due to disease and chelating agents. Issue of iron overload among thalassemic patients can be reduced by decreasing the need or the frequency of blood transfusions.

Demographic and Socioeconomic Profile of Transfusion Dependent Beta-Thalassemia Major Patients in Sabah

@# Thalassemia prevalence in Malaysia is highest in Sabah. This study was conducted to characterize the demographic and socioeconomic profile of transfusion-dependent β-thalassemia major patients in Sabah, to explore their parents’ background, and to identify factors associated with having more than one thalassemia major children in the family. Methods: This was a cross-sectional study conducted in Hospital Wanita dan Kanak-Kanak Sabah and Hospital Kota Belud Sabah between February 2018 and Jun 2019. A total of 108 patients attending Thalassemia Treatment Clinic at both centers were selected randomly for interview. Results: β-thalassemia major patients in this study were majority from the indigenous ethnic groups (Kadazan, Dusun, Murut, Rungus, Sungai). Parents of the thalassemia patients mostly had low education level and socioeconomic status. Thirty-seven percent of parents have more than one children with thalassemia major and a high proportion (41.7%) have intermarriages. Parents with a higher number of children in the family are associated with having more than one thalassemia major children (OR: 2.1, 95% CI: 1.5, 2.9, P-value = 1.3 x 10-5). Conclusions: A considerably high proportion of parents have more than one children with thalassemia major in this study. Knowledge and counselling are important to parents with low educational level and socioeconomic status to ensure their understanding of thalassemia risk and prevention

Ocular abnormalities in multi‑transfused beta‑thalassemia patients.

Aims: The aim of this study was to assess ocular changes in thalassemia patients who have received multiple transfusions and chelate binding therapy in order to avoid iron accumulation. Settings and Design: A cross‑sectional study. Subjects and Methods: A total of 54 thalassemia major patients were selected as case group, and 54 age‑ and sex‑matched healthy subjects were regarded as a control group. Ocular examination included visual acuity, refraction testing, slit lamp examination, funduscopy, tonometry, perimetry, tear break‑up time test, and color vision testing were performed for all the participants. We computed the frequency and duration of blood transfusion, the mean serum ferritin level, pretransfusion hemoglobin concentration, and type, duration, and daily dose of chelation therapy for thalassemia patients based on their records. Statistical Analysis Used: All data analysis was performed using SPSS, version 19. Results: All the thalassemic patients were asymptomatic, but abnormal ocular findings (dry eye (33.3%), cataract (10.2%), retinal pigment epithelium degeneration (16.7%), color vision deficiency (3.7%), and visual field defects (33.7%)) were seen in 68.5% of thalassemic group. The prevalence of ocular abnormalities in normal group was 19.4%, which was significantly lower than that in thalassemia patients (P = 0.000). No significant correlation was found between ocular abnormalities and mean serum ferritin level (P = 0.627) and mean hemoglobin concentration (P = 0.143). Correlation of number of blood transfusion with the presence of ocular abnormalities was found to be statistically significant (P = 0.005). Conclusions: As life expectancy for beta‑thalassemia patients extends, regular ophthalmological evaluation to detect early changes in their ocular system is recommended.

Iron chelation therapy in beta-thalassemia major: a systematic review with meta-analysis / 中国药学杂志

OBJECTIVE: The efficacy and safety of deferrioxamine (deferoxamine, DFO) and deferiprone(DFP) has been widely reported and researched so far, some scholars have reported the efficacy of the combination of the two drugs, but it is still lack of adequate research to prove the efficacy between combination therapy and single administration. This study is evaluate the efficacy of deferrioxamine, deferiprone and combination therapy in beta-thalassemia major patients. METHODS: The randomized controlled trials (RCT) were collected from the Cochrane library, PubMed, EMBASE, CBM, CNKI and VIP, etc. Serum ferritin(SF), liver iron concentration (LIC), urinary iron excretion(UIE), ejection fraction (EF) and myocardial iron concentration (MIC) were chosen as evaluation index to evaluate the efficacy. Studies were screened, data were extracted, and the methodological quality was assessed by two reviewers independently. Meta-analyses were conducted by using RevMan 5.0 software. RESULTS: Nine randomized controlled studies involving 654 patients were included. The results showed that compared with the group of single administration of either deferiprone or deferoxamine, the experimental group of deferiprone combined with deferoxamine was superior in the following aspects with significant differences: Serum ferritin levels [WMD = - 215.37, 95% CI (- 395.35, - 35.39), P = 0.02], liver iron concentration [SMD = - 1.06, 95%CI(- 1.54, - 0.58), P < 0.0001], urinary iron excretion [SMD = 1.04, 95% CI(0.61, 1.47), P < 0.00001], ejection fraction[WMD = 3.37, 95% CI (0.79, 5.95), P = 0.01]. But no statistically significant variation in myocardial iron concentration between deferoxamine combined with deferiprone and monotherapy [WMD = 1.70, 95%CI(- 2.78, 6.18), P = 0.46]. There was no statistically significant variation in serum ferritin[WMD = 133.45, 95% CI (- 48.92, 315.82), P = 0.15], ejection fraction [WMD = 0.96, 95%CI(- 2.74, 4.66), P = 0.40], myocardial iron concentration [WMD = 1.50, 95%CI(- 1.70, 4.70), P = 0.36] during deferoxamine versus deferiprone treatment. CONCLUSION: According to the domestic evidence, deferoxamine combined with deferiprone for treating beta-thalassemia major is superior to deferoxamine or deferiprone monotherapy. It provides a new and prospective therapeutic method for beta-thalassemia major. However, for the quality restrictions of the included studies, this conclusion has to be further verified by high quality, large scale and double blinded randomized controlled trials.

Attenuation of Serum Ferritin and Iron Burden by Intake of Antioxidants in Beta Thalassemia Major.

It has been anticipated that iron and ferritin burden in patients with beta thalassemia major is associated with enhanced free radical formation and blemished antioxidant defense system. The goal of study was to scrutinize impact of serum iron, total iron binding capacity (TIBC), ferritin and erythrocyte catalase in patients with beta thalassemia major. 140 beta thalassemia major patients were studied before and after supplementation of antioxidants for one month, and status was compared with 140 age and sex matched healthy controls. A significant elevation was found in the levels of serum iron and ferritin (P<0.001) with concomitant decrease in erythrocyte catalase (P<0.001) in patients when compared with controls. After one month supplementation of antioxidants, catalase was elevated significantly (P<0.001) and marginal rise in serum TIBC concentration increased marginally while iron and ferritin were decreased marginally (P>0.05) when compared with controls and baselines values. Beta thalassemia major children receive multiple blood transfusions, and are at risk of secondary iron overload induced oxidative stress. These effects may be help to minimize with supplementation of antioxidants.