Valutazione della densitometria ossea in pazienti beta-talassemiche sottoposte a terapia con raloxifene

Abbiamo condotto uno studio sul trattamento con raloxifene cloridrato, per un periodo di follow-up della durata di 2 anni, su un gruppo di pazienti affette da talassemia intermedia e major, al fine di valutare mediante densitometria minerale ossea (BMD), se la terapia è efficace in termini di riduzione della perdita ossea. Dai nostri dati è emerso che non ci sono state differenze significative in termini di miglioramento della percentuale di perdita ossea, contrariamente a quanto si verifica in donne in menopausa senza problemi ematologici. Al momento attuale, la terapia in grado di migliorare o mantenere una buona qualità di vita di queste pazienti, si basa su un regime trasfusionale precoce, continuo e con livelli di emoglobina ottimali, su un’adeguata terapia chelante, sull’astenzione dal fumo e su una valida e costante attività fisic

Gravidanza in pazienti emoglobinopatiche e non emoglobinopatiche: studio comparativo

L’anemia in corso di gravidanza è molto frequente ed è considerata un fattore di rischio sia per la madre che per il feto. Tra le varie forme di anemia che intercorrono in gravidanza un ruolo fondamentale gioca l’anemia ferrocarenziale. L’anemia sideropenica costituisce un serio problema di salute pubblica, considerato il significativo impatto sullo sviluppo fisico di ciascun individuo, per rapporti sociali e sul rendimento dell’attività lavorativa. Il nostro lavoro si propone i seguenti scopi: i) valutare la condizione ematologica delle pazienti in gravidanza che afferiscono al nostro Servizio di Talassemia, ii) dare l’esatta collocazione nosografia al tipo di anemia, iii) individuare i possibili protocolli terapeutici più idonei al trattamento, con l’obiettivo finale di monitorare l’andamento della gravidanza e prevenire l’insorgenza di complicanze. Sono state arruolate 44 donne gravide alla X settimana di età gestazionale. Sono state escluse le pazienti in trattamento parenterale con ferro prima dell’arruolamento e intolleranza ai derivati del ferro, pazienti affette da Celiachia, pazienti portatrici di emoglobinopatia con anemia microcitica normo/ipersideremica secondaria a deficit eritropoietico midollare, pazienti con anemia correlata a quadri di asma, cirrosi epatica, gravidanze multiple, rischio di nascita prematura, infezioni acute. Le pazienti sono state suddivise in due gruppi: portatrici di beta-talassemia e pazienti negative per emoglobinopatie. I risultati del nostro studio dimostrano una maggiore efficacia della terapia parenterale con ferro gluconato rispetto alla terapia per os in corso di gravidanza, sia per i minori effetti collaterali e/o reazioni anafilattiche, che per il più rapido innalzamento dei valori di emoglobina (p<0.000)

The use of hydroxyurea in the real life of MIOT network: an observational study

Background Hydroxyurea (HU) has been widely used in clinical practice to manage patients with non-transfusion dependent thalassemia (NTDT). Few data are available about the effects of its administration in Italian patients. We assessed hematological and non-hematological outcomes following short- and long-term exposure to HU. Research design and methods We considered 71 NTDT patients (30 females) enrolled in the Myocardial Iron Overload in Thalassemia Network and treated for >12 months with HU. Results The mean duration of HU treatment was 8.23 +/- 5.79 years, starting at a mean age of 37.02 +/- 12.06 years. A significant increase in hemoglobin and mean corpuscular volume values and a down-regulation of all erythropoietic and/or hemolysis indices were detected after at least 12 months of treatment. In 28 patients the hemoglobin increase was >= 1.0 g/dl, associated with a higher HU dose. The hematological response dropped in long-term treatment. A favorable impact of HU treatment in limiting the progression of several complications typical of NTDT syndrome was observed. Conclusion Our findings seemed to suggest that in several NTDT patients HU could be still a valid option to limit the advance in overall disease clinical burden without carrying significant adverse events and increase in mortality

Pancreatic T2* Magnetic Resonance Imaging for Prediction of Cardiac Arrhythmias in Transfusion-Dependent Thalassemia

We assessed the value of pancreatic T2* magnetic resonance imaging (MRI) for predicting cardiac events from a large prospective database of transfusion-dependent thalassemia (TDT) patients. We considered 813 TDT patients (36.47 ± 10.71 years, 54.6% females) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. MRI was used to measure hepatic, pancreatic, and cardiac iron overload (IO), to assess biventricular function and atrial dimensions, and to detect replacement myocardial fibrosis. The mean follow-up was 50.51 ± 19.75 months. Cardiac complications were recorded in 21 (2.6%) patients: one with heart failure (HF) and 20 with arrhythmias. The single patient who developed HF had, at the baseline MRI, a reduced pancreas T2*. Out of the 20 recorded arrhythmias, 17 were supraventricular. Pancreatic T2* values were a significant predictor of future arrhythmia-related events (hazard ratio = 0.89; p = 0.015). Pancreas T2* remained significantly associated with future arrhythmias after adjusting for any other univariate predictor (age and male sex, diabetes, history of previous arrhythmias, or left atrial area index). According to the receiver-operating characteristic curve analysis for arrhythmias, a pancreas T2* < 6.73 ms was the optimal cut-off value. In TDT, pancreatic iron levels had significant prognostic power for arrhythmias. Regular monitoring and the development of targeted interventions to manage pancreatic IO may help improve patient outcomes

National networking in rare diseases and reduction of cardiac burden in thalassemia major

Aims: A tailored chelation therapy guided by magnetic resonance imaging (MRI) is a strategy to improve the prognosis in iron-loaded patients, in many cases still hampered by limited MRI availability. In order to address this issue, the Myocardial Iron Overload in Thalassemia (MIOT) network was established in Italy and we aimed to describe the impact of 10-year activity of this network on cardiac burden in thalassemia major (TM). Methods and results: Within the MIOT network, 1746 TM patients (911 females; mean age 31.2 ± 9.1 years) were consecutively enrolled and prospectively followed by 70 thalassemia and 10 MRI centres. Patients were scanned using a multiparametric approach for assessing myocardial iron overload (MIO), biventricular function, and myocardial fibrosis. At the last MRI scan, a significant increase in global heart T2* values and a significantly higher frequency of patients with no MIO (all segmental T2* ≥20 ms) were detected, with a concordant improvement in biventricular function, particularly in patients with baseline global heart T2* <20 ms. Forty-seven percentage of patients changed the chelation regimen based on MRI. The frequency of heart failure (HF) significantly decreased after baseline MRI from 3.5 to 0.8% (P < 0.0001). Forty-six patients died during the study, and HF accounted for 34.8% of deaths. Conclusion: Over 10 years, continuous monitoring of cardiac iron and a tailored chelation therapy allowed MIO reduction, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related HF. A national networking for rare diseases therefore proved effective in improving the care and reducing cardiac outcomes of TM patients. Key question: Which was the impact on cardiac outcomes in thalassemia major by a national network among thalassemia and magnetic resonance imaging centres ensuring the continuous and standardized monitoring of the cardiac iron levels? Key finding: There was a reduction of myocardial iron overload (MIO) in almost 70% of patients, with consequent improvement of cardiac function and reduction of cardiac complications and mortality from MIO-related heart failure. Take home message: A national clinical and imaging networking in rare diseases was effective in improving the care and in reducing the cardiac burden in thalassemia major patients

Thalassaemia is paradoxically associated with a reduced risk of in-hospital complications and mortality in COVID-19: Data from an international registry

Although numerous patient-specific co-factors have been shown to be associated with worse outcomes in COVID-19, the prognostic value of thalassaemic syndromes in COVID-19 patients remains poorly understood. We studied the outcomes of 137 COVID-19 patients with a history of transfusion-dependent thalassaemia (TDT) and transfusion independent thalassaemia (TIT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID-19 patients with no history of thalassaemia. The mean age of thalassaemia patients included in our study was 41 +/- 16 years (48.9% male). Almost 81% of these patients suffered from TDT requiring blood transfusions on a regular basis. 38.7% of patients were blood group O. Cardiac iron overload was documented in 6.8% of study patients, whereas liver iron overload was documented in 35% of study patients. 40% of thalassaemia patients had a history of splenectomy. 27.7% of study patients required hospitalization due to COVID-19 infection. Amongst the hospitalized patients, one patient died (0.7%) and one patient required intubation. Continuous positive airway pressure (CPAP) was required in almost 5% of study patients. After adjustment for age-, sex- and other known risk factors (cardiac disease, kidney disease and pulmonary disease), the rate of in-hospital complications (supplemental oxygen use, admission to an intensive care unit for CPAP therapy or intubation) and all-cause mortality was significantly lower in the thalassaemia group compared to the matched cohort with no history of thalassaemia. Amongst thalassaemia patients in general, the TIT group exhibited a higher rate of hospitalization compared to the TDT group (p = 0.001). In addition, the rate of complications such as acute kidney injury and need for supplemental oxygen was significantly higher in the TIT group compared to the TDT group. In the multivariable logistic regression analysis, age and history of heart or kidney disease were all found to be independent risk factors for increased in-hospital, all-cause mortality, whereas the presence of thalassaemia (either TDT or TIT) was found to be independently associated with reduced all-cause mortality. The presence of thalassaemia in COVID-19 patients was independently associated with lower in-hospital, all-cause mortality and few in-hospital complications in our study. The pathophysiology of this is unclear and needs to be studied in vitro and in animal models