Good Clinical Practice of the Italian Society of Thalassemia and Haemoglobinopathies (SITE) for the Management of Endocrine Complications in Patients with Haemoglobinopathies.

BACKGROUND: The treatment of endocrinopathies in haemoglobinopathies is a continually expanding research area; therefore, recommendations supporting the appropriateness of treatments are a pressing need for the medical community. METHODS: The Management Committee of SITE selected and gathered a multidisciplinary and multi-professional team, including experts in haemoglobinopathies and experts in endocrinopathies, who have been flanked by experts with methodological and organizational expertise, in order to formulate recommendations based on the available scientific evidence integrated by personal clinical experience. The project followed the systematic approach for the production of clinical practice guidelines according to the methodology suggested by the National Center for Clinical Excellence, Quality and Safety of Care (CNEC). RESULTS: Out of 14 topics, 100 clinical questions were addressed, and 206 recommendations were elaborated on. The strength of recommendations, panel agreement, a short general description of the topic, and the interpretation of evidence were reported. CONCLUSIONS: Good Practice Recommendations are the final outcome of translational research and allow one to transfer to the daily clinical practice of endocrine complications in haemoglobinopathies.

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.

Influenza Vaccination in Asplenia: Improving Quality of Care in Time of Coronavirus

IntroductionAsplenic patients are at high risk of potentially fatal invasive infections, such as sepsis, meningitis, and pneumonia. It has been shown that infection from influenza viruses can precede or increase the risk of bacterial infection and of serious complications of the underlying disease. International and national guidelines recommend annual influenza vaccination in asplenic subjects. Following the Covid-19 pandemic, the major government and medical-scientific institutions in the US and in Europe have been planning how to contain infection during the 2020-2021 influenza season. Extending influenza vaccination is the safest and most effective way to reduce the circulation of influenza virus and to promote the correct diagnosis and management of suspected cases of SARS-CoV-2. Influenza vaccination also reduces complications associated with the underlying disease and visits to Emergency Units. Our study aims to evaluate influenza vaccination in a large population of asplenic patients and explore the main causes for non-vaccination to identify critical areas for improvement in the vaccination programme in these at-risk patients for the 2020-2021 influenza season.MethodsThe Italian Network of Asplenia (INA) is made up of 88 doctors working in 50 clinical centers in 27 cities and 16 of the 20 regions of Italy. It aims to build a large, prospective cohort of asplenic patients throughout Italy through which to study the interaction between asplenia and its associated underlying conditions, collecting precise, accurate data also in cases of rarer diseases. The study also aims to improve the quality of healthcare for this at-risk population. The number of patients enrolled in the Network who had had at least one dose of influenza vaccine at the time of diagnosis of asplenia was retrieved from the INA database. All participating centers were asked to answer a questionnaire to report the main obstacles for influenza vaccination.ResultsAt 1st August 2020, 1,670 patients had been enrolled in the INA (783 females;887 males). All underlying causes of asplenia are shown in Table 1. Only 466 (28%) patients had had at least one influenza vaccination, while 1,204 (72%) had never been vaccinated since diagnosis of asplenia. Thirty-five (70%) of the 50 centers answered the questionnaire. Main causes of non-vaccination were physicians' ambivalence concerning vaccination and patients' inadequate awareness or logistical problems.ConclusionsThese data show very low seasonal influenza vaccination cover even though asplenic patients are considered at-risk of complications associated with infection from influenza viruses. Since the 2020-2021 influenza season could see influenza viruses in circulation with SARS-CoV-2, influenza vaccination must be expanded as widely as possible, in particular to subjects of all ages at high risk. These results reveal important areas of concern in the management of asplenic patients and the need to improve the quality of information to physicians and patients alike. The INA co-ordinating center will launch a campaign to provide information and organize ad hoc meetings to widen influenza vaccination coverage in asplenic patients and reduce the pressure on the national health service during the next influenza season.

COVID 19 and Hemoglobinopathies: Update of the Italian Experience

Background. Patients with pre-existent chronic morbidities are likely to be more severely affected by SARS-Cov2 infection. In Italy, the "Società Italiana Talassemie ed Emoglobinopatie" (SITE) has recently estimated the number of patients (Pts) with Hemoglobinopathies followed by Italian Specialized Centers (SITE Network). Five thousand Transfusion-dependent beta-thalassemia (TDT), 1900 Non-Transfusion-dependent beta-thalassemia (NTDT) and 2000 Sickle Cell Disease (SCD) were registered [1]. To verify the impact of SARS-CoV-2 infection on Pts with Hemoglobinopathies, we performed a specific survey by electronic Case Report Form (eCRF). Inclusion criteria included positive swab or serology in a patient with hemoglobinopathy and at least 15 days of follow-up from either the onset of symptoms or SARS-CoV2 positivity. The survey was approved by the Ethics Committee, and eCRF was shared with the Centers of Italian Hemoglobinopathies Network. Preliminary data updated to April 10, 2020, were published [2].Results. As of July 31, 2020, 27 cases have been reported: 18 TDT, 4 NTDT, 5 SCD. 89% of the cases were in Northern Italy, where the rate of infection was much higher than the rest of the country, reflecting the national epidemiology. The mean age of thalassemia patients (TDT and NTDT) was 43±11 years, and 55% were male;the mean age of SCD patients was 33±15 years, and 40% was male. The likely source of infection has been detected in 63% (17/27) of cases: 11 had occupational exposure, 6 had a positive relative. Five patients were asymptomatic: for them, the SARS-CoV-2 infection was identified by positive swab for 1 patient and by positive level of IgG for 4. Twenty patients had associated comorbidities, 14 were splenectomized, and 3 had functional asplenia. Eleven patients were hospitalized, only one in high-intensity care unit. Three patients required more intensive ventilation support with continuous positive airway pressure (CPAP), one of these has a history of diffuse large B-cell lymphoma treated with chemotherapy in the previous year. Three other patients required support by oxygen. No Pts required intubation. Two Pts increased blood requirement. Only five received supposedly specific treatment for COVID-19: two hydroxychloroquine (HCQ), one HCQ plus ritonavir/darunavir, and one HCQ plus anakinra, one HCQ plus Tocilizumab plus Lopinavir/Ritonavir. The clinical course of hospitalized patients was 18±7 days. All patients recovered.Conclusions. The prevalence of COVID-19 infection in Italian patients with Hemoglobinopathies result 0,3% while in general population the prevalence in Italy is 0,4% [3]. Considering that the thalassemia population is more strictly observed, we could postulate that the precautions suggested or self-applied by the Pts were effective. No death nor severe SARS with intubation, nor signs of cytokines storm, only one thromboembolic event was observed although most individuals had pre-existing complications. A single case with pulmonary hypertension has been described in detail [4]. In most individuals the infection has been pauci or asymptomatic and all recovered. This experience differs from what has been observed in Iran on a similar series with different severity and mortality and ask for a more in-depth comparison [5]. In conclusion, our data do not indicate increased severity of COVID-19 in Pts with Hemoglobinopathies followed in Specialized Centers.Acknowledgment. We would like to thank ALT (Associazione per la Lotta alla Talassemia R.Vullo - Ferrara)..References1. http://www.site-italia.org/2020/covid-19.php. SITE communication. Accessed April 1, 20202. Motta I, Migone De Amicis M, Pinto VM, et al. SARS-CoV-2 infection in beta thalassemia: Preliminary data from the Italian experience. Am J Hematol. 2020;95(8): E198-E199.3. https://www.epicentro.iss.it/coronavirus/sars-cov-2-dashboard, Accessed July 31, 20204. Pinto VM, Derchi GE, Bacigalupo L, Pontali E, Forni GL. COVID-19 in a Patient with β-Thalassemia Major and Severe Pulmonary Arterial Hypertension. Hemoglobin. 2020;44(3):218-220 5. Karimi M, Haghpanah S, Azarkeivan A, et al. Prevalence and mortality in β-thalassaemias due to outbreak of novel coronavirus disease (COVID-19): the nationwide Iranian experience. Br J Haematol. 2020;190(3):e137-e140.

COVID-19 in a Patient with ß-Thalassemia Major and Severe Pulmonary Arterial Hypertension.

We here report the successful recovery from coronavirus disease-19 (COVID-19) pneumonia in a patient with ß-thalassemia major (ß-TM) and severe pulmonary arterial hypertension (PAH), focusing on the patient's comorbidities, therapeutic course and drug interaction.