Preliminary data on COVID-19 in patients with hemoglobinopathies : A multicentre ICET-A study

Objectives: This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings, and outcomes of COVID-19 in patients with transfusion-dependent β thalassemia major (TM), β-thalassemia intermedia (TI) and sickle cell disease (SCD). Design: A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies, participated in the survey. Main outcome data: Clinical, laboratory, and radiologic findings and outcomes of patients with COVID-19 were collected from medical records and summarized. Results: A total of 13 patients, 7 with TM, 3 with TI, and 3 with SCD, with confirmed COVID-19, were identified in 6 Centers from different countries. The overall mean age of patients was 33.7±12.3 years (range:13-66); 9/13 (69.2%) patients were females. Six patients had pneumonia, and 4 needed oxygen therapy. Increased C-reactive protein (6/10), high serum lactate dehydrogenase (LDH; 6/10), and erythrocyte sedimentation rate (ESR; 6/10) were the most common laboratory findings. 6/10 patients had an exacerbation of anemia (2 with SCD). In the majority of patients, the course of COVID-19 was moderate (6/10) and severe in 3/10 patients. A 30-year-old female with TM, developed a critical SARS-CoV-2 infection, followed by death in an Intensive Care Unit. In one Center (Oman), the majority of suspected cases were observed in patients with SCD between the age of 21 and 40 years. A rapid clinical improvement of tachypnea/dyspnea and oxygen saturation was observed, after red blood cell exchange transfusion, in a young girl with SCD and worsening of anemia (Hb level from 9.2 g/dl to 6.1g/dl). Conclusions: The data presented in this survey permit an early assessment of the clinical characteristics of COVID 19 in different countries. 70% of symptomatic patients with COVID-19 required hospitalization. The presence of associated co-morbidities can aggravate the severity of COVID- 19, leading to a poorer prognosis irrespective of age

A retrospective long-term study on age at menarche and menstrual characteristics in 85 young women with Transfusion-Dependent β-Thalassemia (TDT)

Background: Menarche is an important milestone in a feminine reproductive life, and regular menstrual cycles reflect normal functioning of the hypothalamic-pituitary-ovarian axis, a vital sign of women's general health. Aim of the study: We explored the age at menarche and the following menstrual cycles characteristics among 85 unmarried Transfusion-Dependent β-Thalassemia (TDT) women, born between 1965 and 1995, concerning iron chelation therapy (ICT) with desferrioxamine (DFO) and nutritional status, assessed by body mass index (BMI). Results: 53 adolescents who had begun ICT before the age of 10 years experienced menarche at 13,7 ± 1,6 years (mean ± DS), whereas 32 who began treatment after ten years experienced menarche significantly later (15.5 ± 1.9 yrs; p: 0.001). At the age of menarche: BMI-Z score (n= 67, - 0,09 ±1) was inversely correlated with both age at starting ICT (r = - 0,39; p = 0001) and age at menarche (- 0,45, p = 0,0001). Serum ferritin levels (SF) were significantly correlated with the age at starting chelation therapy (n = 79; r = 0,34; p = 0,022). In 56 TDT adolescents who developed secondary amenorrhea (SA), the SF levels were significantly higher (4,098 ± 1,907 ng/mL) compared to 23 TDT adolescents with regular menstrual cycles (2,913±782 ng/mL; p = 0,005). Nutritional status of "thinness" at menarche was associated with a lower prevalence of subsequent regular menstrual cycles and a higher prevalence of early SA. Conclusion: An early ICT in TDT patients was associated with a normal "tempo" of pubertal onset and a higher frequency of subsequent regular menstrual cycles. In TDT patients, who developed SA, a diagnosis of acquired central hypogonadism was made, mainly due to the chronic exposure to iron overload, however other potential causes linked to nutritional status, deficient levels of circulating nutrients, and the chronic disease itself cannot be fully excluded

Evaluation of endocrine complications in beta-thalassemia intermedia (β-TI): a cross-sectional multicenter study

Background: Data on the prevalence and type of endocrine disorders in β-thalassemia intermedia (β-TI) patients are scarce. This multicenter study was designed to determine the prevalence of endocrine complications and the associated risk factors in a large group of β-TI patients. Methods: In this cross-sectional multicenter study, 726 β-TI patients, aged 2.5–80 years, registered at 12 thalassemic centers, from nine countries, were enrolled during 2017. In a subgroup of 522 patients (mean age 30.8 ± 12.1; range: 2.5–80 years) from Qatar, Iran, Oman, Cyprus, and Jordan detailed data were available. Results: Overall, the most prevalent complications were osteopenia/osteoporosis (22.3%), hypogonadism (10.1%), and primary hypothyroidism (5.3%). In the subgroup multivariate analysis, older age was a risk factor for osteoporosis (Odds ratio: 7.870, 95% CI: 4.729–13.099, P < 0.001), hypogonadism (Odds ratio: 6.310, 95% CI: 2.944–13.521, P < 0.001), and non-insulin-dependent diabetes mellitus (NIDDM; Odds ratio: 17.67, 95% CI: 2.217–140.968, P = 0.007). Splenectomy was a risk factor for osteoporosis (Odds ratio: 1.736, 95% CI: 1.012–2.977, P = 0.045). Hydroxyurea was identified as a “protective factor” for NIDDM (Odds ratio: 0.259, 95% CI: 0.074–0.902, P = 0.034). Conclusions: To the best of our knowledge, this is the largest cohort of β-TI patients with endocrine disorders evaluated in extremely heterogenic thalassemic populations for age, clinical, hematological, and molecular composition. The study demonstrates that endocrine complications are less common in patients with β-TI compared with β-TM patients. However, regular monitoring with timely diagnosis and proper management is crucial to prevent endocrine complications in β-TI patients. © 2019, Springer Science+Business Media, LLC, part of Springer Nature

Marital status and paternity in patients with Transfusion- Dependent Thalassemia (TDT) and Non Transfusion- Dependent Thalassemia (NTDT): An ICET - A survey in different countries

Background: More than five decades ago, thalassemia major (TDT) was fatal in the first decade of life. Survival and quality of life have improved progressively thanks to the implementation of a significant advance in diagnostic and therapeutic methods, consisting mainly of a frequent transfusion program combined with intensive chelation therapy. Improvement also includes imaging methods used to measure liver and cardiac iron overload. Improved survival has led to a growing number of adults requiring specialised care and counselling for specific life events, such as sexual maturity and acquisition of a family. Aims of the study: The main aim is to present the results of a survey on the marital and paternity status in a large population of adult males with TDT and NTDT living in countries with a high prevalence of thalassemia and a review of current literature using a systematic search for published studies. Results: Ten out of 16 Thalassemia Centres (62.5%) of the ICET-A Network, treating a total of 966 male patients, aged above 18 years with β- thalassemias (738 TDT and 228 NTDT), participated in the study. Of the 966 patients, 240 (24.8%) were married or lived with partners, and 726 (75.2%) unmarried. The mean age at marriage was 29.7 ± 0.3 years. Of 240 patients, 184 (76.6%) had children within the first two years of marriage (2.1 ± 0.1 years, median 2 years, range 1.8 - 2.3 years). The average number of children was 1.32 ± 0.06 (1.27 ± 0.07 in TDT patients and 1.47 ± 0.15 in NTDT patients; p: >0.05). Whatever the modality of conception, 184 patients (76.6%) had one or two children and 1 NTDT patient had 6 children. Nine (4.8%) births were twins. Of 184 patients, 150 (81.5%) had natural conception, 23 (12.5%) required induction of spermatogenesis with gonadotropins (hCG and hMG), 8 (4.3%) needed intracytoplasmic sperm injection (ICSI) and 3 adopted a child. 39 patients with TDT and NTDT asked for medical help as they were unable to father naturally: 7 TDT patients (17.9%) were azoospermic, 17 (37.7%) [13 with TDT and 4 with NTDT] had dysspermia and 15 (33.3%) [13 with TDT and 2 with NTDT] had other “general medical and non-medical conditions”. Conclusions: Our study provides detailed information in a novel area where there are few contemporary data. Understanding the aspects of male reproductive health is important for physicians involved in the care of men with thalassemias to convey the message that prospects for fatherhood are potentially good due to progressive improvements in treatment regimens and supportive care. © 2019, Mattioli 1885. All rights reserved

An ICET-A survey on occult and emerging endocrine complications in patients with β-thalassemia major: Conclusions and recommendations

In adult thalassemia major (TM) patients, a number of occult and emerging endocrine complications, such as: central hypothyroidism (CH), thyroid cancer, latent hypocortisolism, and growth hormone deficiency (GHD) have emerged and been reported. As the early detection of these complications is essential for appropriate treatment and follow-up, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) promoted a survey on these complications in adult TM patients, among physicians (pediatricians, hematologists and endocrinologists) caring for TM patients in different countries. The data reported by 15 countries are presented.The commonest endocrine complications registered in 3.114 TM adults are CH and GHD (4.6 % and 3.0 %, respectively), followed by latent hypocortisolism (1.2%). In 13 patients (0.41%) a cytological papillary or follicular thyroid carcinoma was diagnosed in 11 and 2 patients, respectively, and a lobectomy or thyroidectomy was carried out. Of 202 TM patients below the age of 18 years, the reported endocrine complications were: GHD in 4.5%, latent hypocortisolism in 4.4% and central hypothyrodisim in 0.5%. Transition phase was an area of interest for many clinicians, especially as patients with complex chronic health conditions are responding to new treatments extending their lifespan beyond imagination.. In conclusion, our survey provides a better understanding of physicians’ current clinical practices and beliefs in the detection, prevention and treatment of some endocrine complications prevailing in adult TM patients. Regular surveillance, early diagnosis, treatment and follow-up in a multi-disciplinary specialized setting are recommended. (www.actabiomedica.it). © Mattioli 1885

Preliminary data on COVID-19 in patients with hemoglobinopathies: A multicentre ICET-A study

Objectives: This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings, and outcomes of COVID-19 in patients with transfusion-dependent β thalassemia major (TM), β-thalassemia intermedia (TI) and sickle cell disease (SCD). Design: A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies, participated in the survey. Main outcome data: Clinical, laboratory, and radiologic findings and outcomes of patients with COVID-19 were collected from medical records and summarized. Results: A total of 13 patients, 7 with TM, 3 with TI, and 3 with SCD, with confirmed COVID-19, were identified in 6 Centers from different countries. The overall mean age of patients was 33.7±12.3 years (range:13-66); 9/13 (69.2%) patients were females. Six patients had pneumonia, and 4 needed oxygen therapy. Increased C-reactive protein (6/10), high serum lactate dehydrogenase (LDH; 6/10), and erythrocyte sedimentation rate (ESR; 6/10) were the most common laboratory findings. 6/10 patients had an exacerbation of anemia (2 with SCD). In the majority of patients, the course of COVID-19 was moderate (6/10) and severe in 3/10 patients. A 30-year-old female with TM, developed a critical SARS-CoV-2 infection, followed by death in an Intensive Care Unit. In one Center (Oman), the majority of suspected cases were observed in patients with SCD between the age of 21 and 40 years. A rapid clinical improvement of tachypnea/dyspnea and oxygen saturation was observed, after red blood cell exchange transfusion, in a young girl with SCD and worsening of anemia (Hb level from 9.2 g/dl to 6.1g/dl). Conclusions: The data presented in this survey permit an early assessment of the clinical characteristics of COVID 19 in different countries. 70% of symptomatic patients with COVID-19 required hospitalization. The presence of associated co-morbidities can aggravate the severity of COVID- 19, leading to a poorer prognosis irrespective of age. © 2020 American Society for Microbiology. All rights reserved

Preliminary data on COVID-19 in patients with hemoglobinopathies : A multicentre ICET-A study

Objectives: This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings, and outcomes of COVID-19 in patients with transfusion-dependent β thalassemia major (TM), β-thalassemia intermedia (TI) and sickle cell disease (SCD). Design: A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies, participated in the survey. Main outcome data: Clinical, laboratory, and radiologic findings and outcomes of patients with COVID-19 were collected from medical records and summarized. Results: A total of 13 patients, 7 with TM, 3 with TI, and 3 with SCD, with confirmed COVID-19, were identified in 6 Centers from different countries. The overall mean age of patients was 33.7±12.3 years (range:13-66); 9/13 (69.2%) patients were females. Six patients had pneumonia, and 4 needed oxygen therapy. Increased C-reactive protein (6/10), high serum lactate dehydrogenase (LDH; 6/10), and erythrocyte sedimentation rate (ESR; 6/10) were the most common laboratory findings. 6/10 patients had an exacerbation of anemia (2 with SCD). In the majority of patients, the course of COVID-19 was moderate (6/10) and severe in 3/10 patients. A 30-year-old female with TM, developed a critical SARS-CoV-2 infection, followed by death in an Intensive Care Unit. In one Center (Oman), the majority of suspected cases were observed in patients with SCD between the age of 21 and 40 years. A rapid clinical improvement of tachypnea/dyspnea and oxygen saturation was observed, after red blood cell exchange transfusion, in a young girl with SCD and worsening of anemia (Hb level from 9.2 g/dl to 6.1g/dl). Conclusions: The data presented in this survey permit an early assessment of the clinical characteristics of COVID 19 in different countries. 70% of symptomatic patients with COVID-19 required hospitalization. The presence of associated co-morbidities can aggravate the severity of COVID- 19, leading to a poorer prognosis irrespective of age