Adult Thalassemia Patients Research Articles

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

Alterations of Plasma Metabolomics Profile in Thalassemia Patients with Low Bone Mineral Density

Background: Osteoporosis is commonly found in thalassemia patients; however, its pathogenesis is not thoroughly understood. Metabolomics is the study of metabolites in biofluids, which help to elucidate the underlying mechanism of several metabolic diseases. Nevertheless, plasma metabolomics profiling has not been carefully investigated in thalassemia patients with low bone mineral density (BMD). Objective: To investigate the alterations of plasma targeted metabolomics in adult thalassemia patients with low BMD. Methods: We conducted a cross-sectional study from February 2022 to January 2023 at Outpatient Hematology Clinic, Chiang Mai University. Thalassemia patients, confirmed by HPLC hemoglobin typing, who aged 19-50 years (male) or more than 19 years (premenopausal female) were eligible. Exclusion criteria were (1) current use or history of any bone modifying agent use within 1 year, (2) severe hepatic or renal impairment, (3) active malignancy or infection. Age- and sex-matched with normal body mass index were also recruited as controls. Two-point BMD, plasma targeted metabolomics by using liquid chromatography coupled with mass spectrometry (LC/MS), and serum bone turnover markers, including bone resorption using CTX, and bone formation using P1NP, were assessed. Interested metabolomes included 19 amino acids, 7 free fatty acids, 20 acylcarnitine intermediates of branched-chain amino acids and fatty acids, 37 phospholipid derivatives, and 4 Krebs' cycle metabolomes. Low BMD was defined as a Z-score of less than -2.0 at any site. Outcomes were the alterations of plasma levels of metabolomes among control, thalassemia with normal BMD, and thalassemia with low BMD. Results: There were a total of 80 thalassemia patients and 40 controls recruited. The mean age of patients was 34.8 years (SD 8.7). Twenty-six patients (32.5%) were male. Forty-seven patients (58.8%) were transfusion-dependent thalassemia. Low BMD was detected in 37 patients (47.5%). We found several plasma metabolomes that were significantly changed between controls and thalassemia and further altered when compared between thalassemia with normal BMD and low BMD (Figure 1). Considering plasma amino acids, glutamate level was significantly increased while glutamine level was decreased. Regarding fatty acid-related metabolomes, arachidonic acid level was increased in thalassemia with low BMD. In addition, several fatty acid-derived medium- and long-chain acylcarnitine levels were higher in plasma of thalassemia with low BMD, particularly C14:0 carnitine. Among plasma phospholipid derivatives, phosphatidylinositol (PI) and lysoPI levels were significantly increased in thalassemia with low BMD. Four plasma Krebs' cycle metabolites were not different among groups. Surprisingly, two serum bone turnover markers (CTX and P1NP) were not sensitive for detecting low bone mineral density in thalassemia (Control vs Thalassemia with normal BMD vs Thalassemia with low BMD: CTX 0.27±0.17 vs 0.36±0.20 vs 0.34±0.19 ng/mL, p=0.079 and P1NP 57.2±25.0 vs 57.2±34.0 vs 53.7±26.4 ng/mL, p=0.824). Conclusion: There were several changes in plasma metabolome levels among thalassemia with low BMD, including altered glutamate-glutamine metabolism, impaired fatty acid oxidation, and increased plasma phosphatidylinositol. Interestingly, these changes were found in patients with normal BMD and further increased in patients with low BMD. Our findings suggest the role of plasma metabolomics as non-invasive biomarkers for osteoporotic condition in thalassemia patients.

Cutaneous Manifestations in Adult Thalassemia Patients

Background: A wide range of cutaneous manifestations have been described in thalassemia patients. No studies have been conducted in Southeast Asia where there is a high prevalence of hemoglobin E (Hb E) thalassemia. Objective: The primary objectives of the present study were to determine the prevalence of cutaneous manifestations among adult thalassemia patients and assess how cutaneous findings differ between patients with and without β-thalassemia (β-thal)/Hb E. Secondary objectives were to determine any associations between cutaneous manifestations and clinical or laboratory findings and to evaluate quality of life (QoL). Materials and Methods: The present study was a cross-sectional descriptive study conducted between April 2021 and December 2022 in Thailand. Adults aged 18 years and older with any type of thalassemia were eligible. The authors collected relevant demographic data, cutaneous and laboratory findings, as well as responses to a validated Thai version of the Dermatology Life Quality Index (DLQI). Results: One hundred patients (37% male) were included, with a median age of 33 (IQR of 24, 41) years. Of these, 76% had β-thal/Hb E. Xerosis was the most common cutaneous manifestation at 69%. Hyperpigmentation was more common in patients with β-thal/Hb E than those without at 41% versus 17% (p=0.031). Extramedullary erythropoiesis, xerosis, and serum ferritin were significantly associated with hyperpigmentation. The overall median DLQI score was 0 (IQR 0, 2). Conclusion: Xerosis was the most common cutaneous findings in adult thalassemia patients, and hyperpigmentation was more common in patients with β-thal/Hb E. However, cutaneous changes had low impact on patients’ QoL. Keywords: Thalassemia; Cutaneous manifestations; Hemoglobin E thalassemia

The association of growth differentiation factor-15 levels and osteoporosis in patients with thalassemia

BackgroundIneffective erythropoiesis (IE) is a significant risk factor for osteoporosis in individuals with thalassemia. Growth differentiation factor-15 (GDF15), a biomarker of IE, was found to be elevated in thalassemia patients. This study aimed to examine the association between GDF15 levels and osteoporosis in patients with thalassemia. MethodsA cross-sectional study was conducted in 130 adult patients with thalassemia in Thailand. Bone mineral density (BMD) at the lumbar spine was evaluated by dual-energy X-ray absorptiometry (DXA), and with a Z-score of less than -2.0 SD was defined as osteoporosis. GDF-15 was measured using the enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to examine the associated factors with the development of osteoporosis. Receiver operator characteristic (ROC) curve analysis was used to estimate the threshold of GDF15 in predicting osteoporosis. ResultsOsteoporosis was detected in 55.4% (72/130) of the patients. Advanced age and high GDF15 levels were positively associated with osteoporosis, while an increased hemoglobin level was negatively associated with osteoporosis in patients with thalassemia. In this study, the GDF15 level's ROC demonstrated a good performance in predicting osteoporosis (AUC=0.77). ConclusionsThe prevalence of osteoporosis is high among adult thalassemia patients. Age and high GDF15 levels were significantly associated with osteoporosis in this study. A higher hemoglobin level is associated with a lower risk of osteoporosis. This study suggest that GDF15 could be used as a predictive biomarker for osteoporosis in patients with thalassemia. Adequate red blood cell transfusions and suppression of GDF15 function may be beneficial in preventing osteoporosis.

Evaluation of Thrombin Activatable Fibrinolysis Inhibitor (TAFI) in Patients with β-Thalassemia

Background: Thalassemia is an inherited disorder of hemoglobin (Hb) synthesis that results in reduced or absent production of globin chain. Hypercoagulable state in thalassemia is a well-recognized event. Thrombin activatable fibrinolysis inhibitor (TAFI) is an enzyme considered to play an important role in the regulation of fibrinolysis by the coagulation system. With this background, the present study was conducted to know the role of TAFI as a contributing factor in hemostatic alteration state in adults with β-thalassemia. Aim: The aim of this article is to evaluate the level of TAFI and hematological parameters in splenectomized and non-splenectomized β-thalassemia patients and to compare their levels with normal subjects. Materials and Methods: This case–control study was conducted in 56 adult thalassemic patients. The plasma TAFI level was evaluated by the ELISA technique. Results: There was a significant reduction in TAFI levels in all thalassemic patients when compared with thalassemia minor patients and controls (P < 0.0001). The TAFI level was significantly lower in the splenectomized group when compared with the non-splenectomized group (P < 0.0001), and the TAFI level was significantly lower in the thalassemia major group when compared with the thalassemia intermediate group (P < 0.0001). There was a significantly higher prothrombin time and activated partial thromboplastin time level in thalassemic major and intermediate patients when compared with thalassemia minor patients and controls (P < 0.001). Conclusion: The TAFI enzyme level could be an important predictor for hemostatic alteration. Its level can be considered as a helpful marker for monitoring and follow-up of thalassemic patients for early and proper intervention to minimize complications.

Correlation of Transferrin Saturation and Serum Ferritin with Bone Mass Density in Adult Transfusion Dependent Beta-Thalassemia Patients.

BackgroundThe use of regular blood transfusions and iron chelation therapy to treat thalassemia has improved survival and increased the incidence of osteoporosis. Moreover, iron toxicity is one of the contributing factors that reduce bone mass density in adult transfusion-dependent beta-thalassemia patients. Therefore, this study aims to determine the proportion of low bone mass density in adult thalassemia patients and transferrin saturation, as well as serum ferritin, which correlates to the skeletal condition.MethodsThis is a cross-sectional study conducted in Thalassemia and Hematology Medical Oncology Clinics of Cipto Mangunkusumo Hospital in March 2016. The anthropometric data and hemoglobin levels were obtained before transfusion. Subsequently, the average ferritin levels, bone mineral density, and radiographic results were obtained.ResultsThe percentage of adult thalassemia major and intermedia patients with low bone mass density was 68%. Also, there was a weak inverse correlation between bone mass density and transferrin saturation (r = −0.329, p = 0.01), while no correlation was shown between bone mass density and ferritin (r = −0.088, p = 0.504). The transferrin saturation cutoff point value used to distinguish the incidence of low and normal bone density in patients with transfusion-dependent beta-thalassemia was 89.5%. In addition, there was weak correlation between Singh index and bone mass density (r = 0.273, p = 0.038).ConclusionAmong the transfusion-dependent beta-thalassemia patients, 68% had low bone mass density, which inversely correlated to transferrin saturation. Furthermore, the cutoff value of transferrin saturation to differentiate the incidence of low and normal bone density in thalassemia major compared to thalassemia intermedia was 89.5%. Singh Index correlates weakly with bone mass density and might be used to detect low bone mass density in remote healthcare facilities.

Cardiorenal Syndrome in Thalassemia Patients

Background: Cardiorenal syndrome (CRS) is a serious condition with high morbidity and mortality. Secondary CRS (type 5 CRS) is characterized by the coexistence of cardiac abnormality and renal dysfunction occurring secondarily to a systemic condition. In thalassemia, a common hematologic disease in Thailand, there is limited information about the prevalence of secondary CRS. Therefore, this study aimed to investigate the prevalence and associated risk factors of secondary CRS in thalassemia patients.Method: In this cross-sectional cohort study, 53 adult thalassemia patients in out-patient clinic of Chiang Mai University Hospital since October 2016 to June 2017 were included. A criterion for diagnosis of secondary CRS is based on a system proposed by Ronco and McCullough. Cardiac abnormalities, assessed by clinical presentation of heart failure, chest X-ray, electrocardiogram, and echocardiogram, included acute or chronic heart failure by using definition from 2016 ESC guideline or structural cardiac abnormalities defined by LV remodeling and dysfunction, diastolic dysfunction, chronic abnormalities in cardiac function or cardiomyopathy. Renal dysfunction is defined by acute kidney injury or chronic kidney according to 2012 KDIGO guidelines. Clinical and laboratory (serum NT-proBNP, spot urine protein, spot urine albumin, spot urine electrolytes, 24-hours urine protein, and 24-hour urine electrolytes) data for 2 consecutive visits, at least three months apart, were assessed. We analyzed correlation between patients with and without cardiorenal syndrome by Chi-square for categorical data, T-test and non-parametric test of 2 independent samples for continuous data. We used binary logistic regression model for multivariate analysis.Result: Of 53 thalassemia patients [42 (79.2%) transfusion dependent thalassemia and 11 (20.8%) non-transfusion dependent thalassemia], 16 (30.2%) has secondary CRS. Cardiac abnormalities was detected in 23 patients (43.4%), included acute or chronic heart failure (N=4, 7.5%), or structural cardiac abnormalities (N=23, 43.4%). Thirty-one patients (58.5%) had renal abnormalities. Compared with the non-CRS group, the CRS group had a significant increase in serum NT-proBNP level [median (range) = 101.4 (79.2-545.1) VS. 64.8 (16.7-281.2) ng/ml, p=0.05], 24-hours urine magnesium level [mean (95%CI) = 5.98 (3.91-8.04) VS. 4.42 (3.01-5.83) mEq/24 hr., p=0.042], 24-hours urine protein level [median (range) = 249 (132-1610) VS. 161 (77-324) mg/24 hr., p=0.003], and 24-hours urine albumin level [median (range) = 45 (3-1303) VS. 5 (2-184) mg/24 hr., p=0.006], but significance lower in mean arterial pressure (MAP) [mean (95%CI) = 72.7(67.5-77.8) VS. 79.5(69.8-89.2) mmHg, p=0.041]. In univariate analysis, CRS was associated with pulmonary hypertension (OR 2.33, p=0.019), presence of extramedullary hematopoiesis (EMH) (OR 3.79, p=0.03). Multivariate analysis confirmed the association of cardiorenal syndrome with presence of EMH (OR 6.55, p=0.04), lower MAP (OR 0.869, p=0.012), elevated serum NT-proBNP (OR =1.013, p=0.012), and elevated 24-hour urine magnesium (OR 2.17, p=0.004). There was no correlation of CRS with type of thalassemia, serum ferritin, liver iron concentration, cardiac T2* and type of iron chelating agents.Conclusion: This study has demonstrated that CRS is common in thalassemia patients. Patients with the presence of EMH, low MAP, increased 24-hour urine magnesium level or an elevated serum NT-proBNP level are at high risk for developing CRS. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

An urgent need for improving thalassemia care due to the wide gap in current real-life practice and clinical practice guidelines

Based on Thalassemia International Federation clinical practice guidelines (CPG) for non-transfusion dependent and transfusion dependent thalassemia, several measures should be routinely implemented such as monitoring and surveillance of thalassemia related complications for early detection and proper clinical management. To evaluate the prevalence and the performance of routine surveillance for thalassemia related complications during 2 periods; before and after published CPGs (2012–2014 vs 2015–2017), data from 524 adult thalassemia patients attended at Siriraj hospital were compared among different treating physician groups; thalassemia, private hematology, and internal medicine clinics. Three most common complications were osteopenia/osteoporosis (69.8%), gallstones (67.6%) and abnormal vitamin D level (67.6%). Iron overload has been widely evaluated (93.1%) followed by liver function test (82.3%). However, the rate of evaluation for other complications were significantly reduced and < 25% of patients were evaluated in several complications. Comparing among clinics, the surveillance rate has increased significantly for several endocrine complications only in patients treated at thalassemia clinic but not in others. This study was the first study that evaluated real-world practical management of thalassemia patient in terms of complication surveillance. This different clinical practice has called for an immediate policy change to improve and standardize a care for thalassemia patients in Thailand.

Iron Overload in Transfusion-Dependent Indonesian Thalassemic Patients.

Thalassemia is a genetic disease caused by disruption of globin chain synthesis leading to severe anemia and thus regular blood transfusion is necessary. However, there have been known transfusions-related consequences, including iron overload and multi-organ damage. The aims of this study were to evaluate liver and cardiac function in youth and adult transfusion-dependent Indonesian thalassemic patients and to assess its correlation with serum ferritin levels, as well as T2∗magnetic resonance imaging (MRI). Transfusion-dependent thalassemic (TDT) outpatients (n = 66; mean age, 21.5 ± 7.2 years) were carried out for the complete assessment consisting of blood test including liver enzyme and serum ferritin, followed by electrocardiography (ECG) and echocardiography. Subjects were also divided by serum ferritin levels into three groups: < 2500 ng/mL, 2500–5000 ng/mL, and >5000 ng/mL. Additionally, subgroup analysis in patients with T2∗ MRI assessment was conducted. In terms of age of first blood transfusion, subjects with ferritin >5000 ng/mL were the youngest among others. The alanine aminotransferase (ALT) levels in group with serum ferritin >5000 ng/mL were significantly higher than those of the group with serum ferritin <2500 ng/mL. Additionally, youth and adult TDT patients whose serum ferritin >5000 ng/mL had significantly lower tricuspid annular plane systolic excursion (TAPSE) when compared with those who had serum ferritin <2500 ng/mL. Similarly, TAPSE in patients with moderate cardiac siderosis based on cardiac T2∗ MRI was significantly lower than those without cardiac siderosis. There was significant, but only moderate correlation between serum ferritin and cardiac T2∗ MRI. Based on these findings, it is important to routinely monitor iron accumulation-related complications, including liver and cardiac damage in youth and adult TDT patients.

COGNITIVE IMPAIRMENT DETECTION IN ADULT THALASSEMIA PATIENT USING MOCA-INA

Background: Cognitive impairment in thalassemia patients are prevalent, therefore early detection of cognitive impairment in adult thalassemia patients is crucial for prevention. Montreal Cognitive Assessment (MoCA) is a public domain cognition screening tools that covers all cognitive domains in detecting mild cognitive impairments. Objective: To compare cognitive function between adult thalassemia patients and healty control by using Indonesia version of MoCA test (MoCA-Ina) Methods: This prospective observational analytic with case control study, compared the total scores and scores of each domain of cognition between adult thalassemia patients and healthy subjects at the Medical Hematology Oncology Clinic of Dr. Hasan Sadikin General Hospital, Bandung, Indonesia using MoCA-Ina from August to October 2018. Results: A total of 32 thalassemia subjects and 50 healthy subjects were conducted. A total of 16(50%) subjects in the case group had a value of MoCA-Ina &lt;26, while only 1(2%) healthy control had a value of MoCA-Ina &lt;26. The median total MoCA-Ina score in case and control groups were 25.5 and 27.50 (p &lt;0.001). The median score of memory domains, executive functions and visuospatial of the case and control groups were 3 versus 4 (p &lt;0.001), 3 versus 3.5 (p &lt;0.001) and 3.53 ± 0.671 versus 3.88 ± 0.385 (p &lt;0.003), respectively. Conclusion: Adults thalassemia patients have lower score in total MoCA-Ina, domains of memory, executive function and visuospatial score compared to healthy control.

Prevalence of Hepatitis B, Hepatitis C, Significant Liver Fibrosis and Its Predictors in Adult Thalassemia Patients who Receive Blood Transfusion

Background: Thalassemia is a common hereditary hematologic disease requiring frequent blood transfusion that increases patient vulnerability to viral hepatitis B and C. Objective: To investigate the prevalence of hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and clinically significant liver fibrosis in adult thalassemia patients who have been receiving blood transfusion, and to identify factors associated with liver fibrosis. Materials and Methods: Patients with thalassemia major and thalassemia intermedia were included. HBV and HCV markers were tested, and patients who were anti-HCV-positive were tested for HCV viral load and HCV genotype. All patients underwent liver transient elastography (TE), and the result was classified as significant fibrosis (&gt;7.1 kPa) or cirrhosis (&gt;12.5 kPa). Results: One hundred and fifty-eight patients (36% male, mean age 38 years) were included. All patients had a history of blood transfusion with a mean life-time transfusion of packed red blood cells of 215 units. Prevalence of HBV and HCV was 1.3% and 5.6%, respectively. The mean TE was 7.9 kPa (range 2.4 to 69.1). Fifty-six patients (34%) had significant liver fibrosis, and 18 (11.4%) had cirrhosis. Factors that correlated with significant liver fibrosis were male gender (odds ratio [OR] 3.4, 95% confidence interval [CI] 1.6 to 7.3), serum ferritin &gt;1,000 ng/mL (OR 3.4, 95% CI 1.5 to 7.6), and abnormal aspartate aminotransferase (AST) (OR 2.9, 95% CI 1.3 to 6.4). Presence of HBV or HCV was not significantly associated with significant fibrosis. Conclusion: Prevalence of HBV in thalassemia patients who receive blood transfusion was comparable to general population, but the prevalence of HCV was higher. About half of the patients had significant fibrosis. Factors associated with significant fibrosis were male gender, serum ferritin &gt;1,000 ng/mL, and abnormal AST. Keywords: Blood transfusion, Prevalence, Hepatitis B, Hepatitis C, Liver fibrosis, Thalassemia

Epidemiology of Thalassemia in Gulf Cooperation Council Countries: A Systematic Review.

Background Thalassemia has a burden on the healthcare systems of many countries. About 56000 conceptions result in thalassemia, globally. Objective To assess the epidemiological profile of thalassemia in the Gulf Cooperation Council (GCC) countries. Methods A systematic search was conducted in MEDLINE/PubMed (National Library of Medicine), CINAHL, and Embase. Relevant observational studies reporting the epidemiology of thalassemia among the GCC population were selected. Data on the prevalence, frequency, and complications of thalassemia were extracted. The quality of the retrieved studies was assessed according to the Newcastle–Ottawa Quality Assessment Scale. Results Eighteen studies (14 cross-sectional studies, two retrospective observational studies, and two retrospective analysis) with a total of 3343042 participants were included in this systematic review. Of the 18 studies, 11 studies were conducted in Saudi Arabia, two in the Kingdom of Bahrain, one in Kuwait, three in the United Arab Emirates (UAE), and one in Qatar. The prevalence of thalassemia among children below five years of age ranged from 0.25% to 33%, while it was 0.9% in children above five years and from 0.035% to 43.3% among adult thalassemia patients. The most-reported risk factors were consanguineous marriage and high-risk marriage. There was a lack of data regarding mortality rates in thalassemia. Conclusions Despite the premarital screening and genetic counseling (PMSGC) program for thalassemia, the incidence of high-risk couple marriages in GCC countries cannot be effectively diminished. This study suggested that the PMSGC program should adopt more attention for the high-risk areas, to enhance the level of consciousness about the hemoglobinopathy diseases and the consequences of consanguinity among the at-risk couple.

Alloimmunization and autoimmunization in adult transfusion-dependent thalassemia patients: a report from a comprehensive center in Israel.

Patients with beta thalassemia major (TM) are transfusion-dependent (TD) since early childhood and for life. Development of alloantibodies and autoantibodies against red blood cell (RBC) antigens is increasingly recognized as a significant transfusion hazard, especially among heavily transfused patients. The aim of this study is to assess RBC alloimmunization and autoimmunization rates in TD TM patients treated in our Comprehensive Center of Adult Thalassemia, Hemoglobinopathies and Rare Anemias. TD TM patients, regularly transfused every 2-3 weeks, were included in the study. Clinical and RBC transfusion records, including RBC antibodies, since diagnosis in early childhood, were retrieved from patients' files and from the blood bank database. Forty TD TM patients, > 18 years of age, were included in the study. Alloimmunization was demonstrated in 17 (42.5%) patients. Thirty-four alloantibodies were detected, with the most frequent being RH related (12 of 34, 35.3%) followed by those of the Kell system (8 of 34, 23.5%). Age at first transfusion was positively related to the probability of developing alloantibodies (p = 0.02). Splenectomy was found to be correlated with developing alloantibodies (p = 0.016). Logistic regression analysis of the lifelong probability of developing alloantibodies on the age at first transfusion and splenectomy demonstrates a strong positive relationship (p = 0.002). A substantially high rate of alloimmunization was found among adult TD TM patients. Early initiation of RBC transfusions, avoidance of splenectomy and extended Rh and K antigen matching, can reduce the incidence of alloimmunization in TD TM patients.

High Tissue Factor Microparticle Level in Major Thalassemic Patients with Pulmonary Hypertension

Objective: To analyze the correlation between tissue factor microparticles (TF-MP) levels and pulmonary hypertension (PH) in adult thalassemic patients. Methods: This study was conducted from September to October 2018, using secondary and primary data. The secondary data consisted of the PH parameter, which was retrieved from a 2017 previous study entitled ‘Clinical Characteristic and Complication due to Iron Overload in Thalassaemic Patients‘in 2017 while the primary data were the TF-MP, which were obtained from the analysis of frozen serum of the same population using ELISA method. The mean pulmonary arterial pressure (mPAP) values were obtained from echocardiography results and PH was defined as mPAP &gt;25 mmHg. Results: Seven (16.7%) major thalassemic patients experienced PH. The median values of TF-MP levels were higher among major thalassemic patients with PH when compared to the non-PH patients (1569 vs 11.5 pg/dL; p=0.023). No significant difference was observed in the median TF-MP levels between subjects with splenectomy and subjects without splenectomy (11.6 vs 12.3 pg/dL; p=0.44). There was also no difference in mPAP values between subjects with splenectomy and subjects without splenectomy (18.0 vs 17.0 mmHg; p=0.663). When the median TF-MP levels among major thalassemic patients were analyzed in terms of correlation with transfusion level, no statistically significant difference was seen between subjects who received sufficient transfusions (≥180 mL/kgbb/year) and those who received insufficient transfusions (&lt;180 mL/kgbb/year) (r= 0.138; p=0.390). Conclusions: There is a positive correlation between the TF-MP levels and PH in adult major thalassemic subjects.

PB2409 QUALITY OF LIFE (QOL) IN TRANSFUSION DEPENDENT (TD) THALASSEMIA ADULTS ON IRON CHELATING THERAPY: AN EGYPTIAN SINGLE CENTER EXPERIENCE

Background:Thalassemia is the commonest type of chronic hemolytic anemia in Egypt. Despite recent advances in the management of thalassemia, people do not receive satisfactory treatment. For such chronic conditions, not only is patients’ survival important but their quality of life (QOL) is also important, which is primarily driven by psychological and social constraints.Aims:This study explores various factors that affect QOL in transfusion‐dependent adult thalassemia patients hence the authorities who provide services to patients, be aware of related mental and social consequences in addition to the burden of the disease to prepare a better living environment for those patients.Methods:We investigated 85 Egyptian adults with transfusion Dependent thalassemia, quality of life (QOL) was assessed using the following questionnaires: short form 36‐item questionnaire (SF‐36), EuroQol Study (EQ‐5D‐3L) questionnaire, visual analogue scale (VAS) questionnaire along with through complete history taking and physical examination with special emphasis on socio‐demographic characters, management details including frequency of transfusion, iron chelation therapy and adequacy, Hepatitis status and does patient had splenectomy or not. This study was conducted at clinical hematology outpatient clinic of internal medicine department, Kasr Alainy school of medicine.Results:we recruited 85 TD adult thalassemia patients (Female were 54%) with median age of 24 years (IQR 20‐28), 20% of them had HCV infection, 90.6% were compliant on iron chelating therapy; 23.4% were on deferoxamine (DFO), 35.1% were on deferasirox (DFX) and 41.6% were on deferiprone (DFP). SF‐36 shows intermediate median score of 52.8 (IQR 43.4‐61.7), better scores in males than females were observed (P value. 037), all aspects of QOL were impaired in our studied patients not only physical problems but also emotional problems with significance decrease in their energy level (IQR 30‐45) and general health (IQR 37.5‐54.1). It was affected by serum ferritin level with lower physical functions with higher serum ferritin level (P value 0.043) was observed. EQ‐5D‐3L questionnaire assessment showed markedly affected mental health domains (anxiety and depression mainly) more than physical health domains, it was observed that type of iron chelators affect healthy utility subscales as mobility domain which was better in patients receiving deferiprone in comparison to other chelators, mobility domain was affected by the age with better scores in older patients (P value 0.002), also VAS questionnaire showed intermediate median score of 50 (IQR 40‐60) among our studied patients and was affected by patients hemoglobin level (P value 0.039) and serum ferritin (P value 0.005)Summary/Conclusion:QOL in our studied TD thalassemia patients was markedly compromised and was affected by gender, age, anemia severity, serum ferritin as well as iron chelator therapies, QOL of assessment should implemented in thalassemia patients care and regularly evaluated, finally our patients and their families require all health utility supports.

PB2412 ADULT THALASSEMIA PATIENTS OF PEDIATRIC HEMATOLOGY CLINIC: A SINGLE CENTER EXPERENCE IN TURKEY

Background:Advances in understanding and treatments in transfusion dependent thalassemia (TDT) improved the clinical outcomes. Disease‐related complications seem to be the challenging problem in aging patients with thalassemia who now survive longer than in the past.Aims:Here we aimed to describe clinical features of adult thalassemia patients followed on the pediatric hematology clinic.Methods:All the patients with TDT and older than 25‐years were reviewed retrospectively. Demogrophical, cilinical features, status of iron overload and treatment and disease related complications were recorded.Results:A total of 69 patients were evaluated. Thirty three were female and 36 were male. Mean age was 32.9 years (range 25‐53 years). Mean duration of follow‐up and iron chelation therapy were 31,2 years (range 14‐50 years), and 25 years (range 7‐ 31 years), respectively.Fortyfour patients had splenectomy. Mean ferritin levels was found to be 1645 ng/ml (range between 361‐8600 ng/ml). Cardiac iron status were evaluated in 44 patients and cardiac T2∗was normal (&gt;20 msec) in 40 patients, moderate and severe iron overload was shown in 1 and 3 patients, respectively. 1 patients had moderate. Liver iron status was normal (&lt;2 mg) in 16 out of 53 patients with liver T2∗ MRI. Liver iron overload was found to be mild (2‐5 mg) in 11 patients, moderate (5‐10 mg) in 10 patients and severe (&gt;10 mg) in 16 patients. A strong positive correleation was found between serum ferritin levels and liver iron overload (p &lt; 0.001). There was no significant association between cardiac iron overload and serum ferritin levels. Also a slight association was shown cardiac and liver iron overload (p = 0.03).Summary/Conclusion:In our country the adult TDT patients are still on follow‐up in pediatric hematology clinics based on the experience of the pediatric hematologists on those patients. Although these older patients were constituted a new cohort, in this study the clinical features and status of iron overload in older TDT patients were found to be acceptable and similar to younger TDT's regarding despite long period of regular transfusion and histroical features of the treatment.

Correlation between Pancreatic MRI T2* and Iron Overload in Adult Transfusion Dependent Beta Thalassemia Patients with Growth Retardation: A Single Centre Study in Indonesia

Correlation Between Pancreatic MRI T2* And Iron Overload in Adult Transfusion Dependent Beta Thalassemia Patients With Growth Retardation: A Single Centre Study in IndonesiaFaizal Drissa Hasibuan, MD1,2, Tb. Djumhana Atmakusuma, MD, PhD3,41Department of Internal Medicine, 2Faculty of Medicine Yarsi University Jakarta, Indonesia, 3Medical Hematology - Oncology Division of Internal Medicine Department Cipto Mangunkusumo Hospital, 4Faculty of Medicine Universitas Indonesia, Jakarta, IndonesiaThe prevalence of thalassemia in Indonesia is one of the highest in the world. It is estimated that the prevalence of beta thalassemia carrier is around 3-10%. In 2016, thalassemia center in Cipto Mangunkusumo Hospital (RSCM) Jakarta recorded 9031 patients suffering from major thalassemia in Indonesia. 441 are adult thalassemia patients (age 18 and above) recorded in Kiara thalassemia and hematology-oncology clinics in RSCM. Based on a survey from TIF, endocrine aspect of the thalassemia patients is often ignored by the clinicians. Growth retarded patients are commonly found in the thalassemia clinic in RSCM. Publication regarding the pancreas and its correlation with iron overload in adult beta TDT patients is currently not available in Indonesia. Therefore, the aim of this study was to describe iron overload condition based on the pancreatic MRI T2* and its correlation with beta TDT adult patients who suffer from growth retardation.A cross sectional study was conducted to determine the prevalence of endocrine disorders in adult TDT beta patients, followed by looking for correlation of excess iron load with endocrine function in adult TDT beta patients with growth retardation in adult Thalassemia clinic RSCM Jakarta on December 2017. Patients with HBsAg or Anti HCV positive were excluded. Excess iron is defined as Transferin Saturation (ST) greater than 50% regardless of serum ferritin or serum ferritin (FS) levels greater than 1000 ng/mL regardless of ST or both.The growth retardation is defined as the standing height of the research subject which is lower than the Mid Parental Height (MPH) value of both parents. Pancreatic MRI T2* used magneto avanto Siemens 1,5T with CMR software.We found from 58 patients who followed the study, 32 patients underwent the pancreatic MRI T2* examination with 13 female (40,6%) and 19 male (59,4%). Patients with homozygous beta thalassemia are 16 people (50%) and beta/HbE thalassemia 16 people (50%). The Proportion of low pancreatic MRI T2* values was found to be 87.5%, with moderate hemosiderosis in 13 patients (40.63%) and severe hemosiderosis not found (Table 2). The age range of the study subjects was relatively young with a median age of 21 years. Although the median body weight of study subjects was 42 kg, the median BMI still included in normal range. Excess iron content in this study was assessed with serum ferritin, obtained median 4982.5 ng/mL and transferin saturation with a median of 100%, indicates the subject of research are in a state of excess iron load. This is due to the possibility of inflammation, inadequate use of chelation, hemolysis in thalassemia, hypertransfusion to achieve the target of 12 g/dL for women and 13 g/dL for men. There was no significant correlation between serum ferritin and pancreatic MRI T2* value, nor did a significant correlation between transferrin saturation with pancreatic MRI T2* value (Table 3). In this study, there was a high proportion of subjects with low pancreatic MRI T2* value of 28 subjects (87,5%), divided into 15 mild hemosiderosis (46,87%), 13 moderate hemosiderosis (40,62%) and none of severe hemosiderosis. Our study is the first study which look for the correlation of the excess iron load (serum ferritin and transferrin saturation) with endocrine function in adult TDT beta patients with retardation of growth in Indonesia. This research has limitations. First, it was a cross sectional study so it is not known exactly the beginning of endocrine disorders in the subject . The second limitation, analysis of iron chelation therapy did not do in this study.Finally, we concluded that there was no correlation between pancreatic MRI T2* and iron overload based on serum ferritin and transferrin saturation. Further longitudinal studies in adult TDT patients with thalassemia who have not and have retarded growth were needed. DisclosuresNo relevant conflicts of interest to declare.

Low-dose Synachten test with measurement of salivary cortisol in adult patients with \u03b2-thalassemia major

PurposeBeta-thalassemia major is a severe, congenital hematological disorder and, if untreated, leads to early mortality. Progress in therapeutical strategies improved clinical outcomes and life expectancy; however, increased survival led to the development of new disorders, including endocrinopathies. Little is known on the possible impairment of adrenocortical function, a potentially life-threatening condition, in long-term thalassaemic survivors. We therefore decided to assess adrenal reserve and the value of salivary cortisol during ACTH stimulation in the diagnosis of adrenocortical insufficiency in adult patients with β-thalassemia major.MethodsCross-sectional study including 72 adults with β-thalassemia major. Patients were tested with 1 µg ACTH for serum and salivary cortisol.ResultsSubnormal serum cortisol responses to ACTH stimulation (i.e., <500 nmol/l) were registered in 15 out of 72 patients. Salivary cortisol increased in parallel with serum cortisol and a clear-cut positive correlation was detected at each timepoint. Moreover, peak salivary cortisol values after ACTH stimulation were significantly lower in patients with impaired adrenal reserve (513.6 ± 52.33 vs. 914.1 ± 44.04 nmol/l p < 0.0001).ConclusionsOur results attest to the need for testing for adrenal insufficiency among adult thalassaemic patients, as up to 20% presented impaired adrenal reserve. Salivary and serum cortisol levels during stimulation with ACTH were closely correlated and the use of salivary cortisol sampling during ACTH testing may represent a surrogate to serum cortisol in these patients.

An Urgent Need for Improving Thalassemia Care in Adult Patients Due to a Wide Gap on Current Real-Life Practice and Recommended Clinical Practice Guidelines

BackgroundThalassemia syndromes are the most common hereditary hemolytic anemia worldwide. Since 2013, Thalassemia International Federation (TIF) has launched new standard clinical practice guidelines (CPG) for non-transfusion dependent thalassemia (NTDT) and transfusion dependent thalassemia (TDT). Based on these guidelines, several measures should be routinely implemented such as monitoring and surveillance of thalassemia related complications in order to early detect such complications for a proper clinical management. At present, there is no data in Thailand to show that how physicians are treating thalassemia patients especially on early detection of all complications and whether their real life practice has changed to follow those of both guidelines.ObjectivesTo evaluate the performance of routine care, in terms of surveillance for thalassemia related complications and their prevalence in adult thalassemia patients during 2 periods; before and after 2 CPG were published.MethodsIn this retrospective study, we analyzed data from 3,233 adult thalassemia patients who were diagnosed and treated at our clinics at Department of Medicine, Siriraj hospital during 1994-2017. We divided them into 2 groups; those who have been treated and followed-up for 3 consecutive years during 2012-2014 and 2015-2017 (a period before and after the implement of CPG, respectively). Clinical data and laboratory results were collected. Complications were recorded including iron overload (IOL) (ferritin), transaminitis (ALT >3x upper normal limit), diabetes mellitus (DM) or impaired fasting glucose (IFG)(fasting blood sugar), hypothyroidism (thyroid function test), low morning cortisol, vitamin D abnormality, viral infection (hepatitis B and C), osteopenia/osteoporosis (bone mineral density, BMD) and gallstones (ultrasonography or CT scan). To compare the performance of routine care from different treating physician groups, patients were categorized into 3 groups; those who attended thalassemia clinic (Thal) treated by mainly staffs and residents in hematology, those in private hematology clinic (Private) treated by mainly attending hematology staffs and residents in hematology, and those in internal medicine clinic (Non-hem) treated by internists and GP. Prevalence and surveillance rates for each complication between groups were analyzed by Independent t test (Chi-square or Fisher's exact test). This study was approved by local ethical committee.ResultsTotal available 459 NTDT and 65 TDT adult patients were studied. Baseline characteristics were shown in Table 1. Three most common complications were osteopenia/osteoporosis (69.8%), gallstones (67.6%) and abnormal vitamin D level (67.6%). IOL is a complication that has been widely evaluated in all treatment groups (93.1%) followed by evaluation of liver function test (82.3%). However the rate of evaluation for other complications were significantly reduced and <25% of patients were evaluated in several complications. This result suggests that the prevalence of thalassemia related complications might be underestimate the true prevalence and early detection of thalassemia related complications is still lacking.To test whether the implement of CPG has any impact on real-life clinical practice, we found that the rate of complication surveillance has increased significantly for several endocrine complications (DM/IFG, hypothyroid, adrenal insufficiency and low vitamin D) only in the group of patients treated at thalassemia clinic but not in others (Figure1). This suggested that CPG have yet to be implemented by those physicians and further endorsement is highly required.ConclusionThis study was the first study that evaluated the real-world practical management of thalassemia patient in terms of complication surveillance. In our adult thalassemia population, thalassemia related complications were not uncommon and some occurred early in adulthood. Surveillance rates of these complications were low in all clinics. After implement of thalassemia CPG, the surveillance rates for complications were increased only in patients treated at thalassemia clinic but not in other two clinics. A two different standard of clinical practice even within the same tertiary care hospital such as Siriraj hospital has called for an immediate policy change to improve and standardize a care for thalassemia patients in Thailand. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Diastolic Dysfunction with Normal Heart T2* in Thalassemia Major with Heart Failure. a Single Centre Study

▪Background Heart failure (HF) is the most important cause of death in Thalassemia Major (TM) patients, and results from iron overload which determines progressive systolic dysfunction of the left ventricle. T2* Magnetic Resonance Imaging (CMR) is the only non-invasive tool for detecting and quantifying myocardial iron storage.We had observed that a large number of Thalassemia patients recently observed at our Centre develops a different form of HF, with evidence of diastolic dysfunction and often in absence of systolic dysfunction.Methods We evaluated the clinical, electrocardiographic, echocardiographic and Doppler data of 16 adult Thalassemia patients with HF observed at our Centre between 2008 and 2016, together with the data obtained by means of T2* CMR. All statistical analyses were descriptive. Results are provided as means ± standard deviations, medians with interquartile ranges (IQR), and percentages.Results Table 1 describes demographics, T2* and Echo-Doppler data of 16 TM patients. The 31.2% were females and the mean age was 44.2±5.7 years.One patient presented systolic dysfunction of the left ventricle whereas the others had echocardiographic and Doppler evidence of diastolic dysfunction. Systolic dysfunction of the right ventricle was also found in 81.25% of cases.Furthermore, 30.75% of cases had T2* values consistent with significant risk for heart failure (≤14 ms), whereas the others had normal values. In 68.75% of the cases ECG showed inversion of T wave beyond V2 lead, and low voltages.Conclusions Most of the patients with heart failure recently observed at our Centre had diastolic dysfunction of the left ventricle with normal systolic function, and impairment of systolic function of the right ventricle, and normal values of cardiacT2*. In 68.75% of cases ECG showed inversion of T wave beyond V2 lead and low voltages. Limitations of this study can be summarizes in: a) small number of cases (16 pts); b) Evidence of normal values of T2* values in most patients does not exclude an iron overload in precedent years. However patients with HF due to systolic dysfunction usually show low or very low values; c) a possible bias of this study may be linked to the Centre where this study has been performed. Our Centre is the Reference Centre of Sicilian Region for Thalassemia patients. This implies the possibility of a very strict surveillance of chelation therapy with frequent evaluations of the data of T2* in order to improve at best the treatment with chelation therapy. It is possible that this, at least in part, might prevent the onset of the classical form of systolic dysfunction of the left ventricle due to iron overload, and that in these patients, differently than in patients followed up in other centres, different forms of HF noit linked to cardiac iron overload may occur: that is heart failure preserved ejection fraction (HFpEF), with prevalent left ventricular diastolic dysfunction. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.