ABSTRACT
BACKGROUND: Ensuring equitable access to adequate standard of care for patients with rare hematological disease is one of the aims of the European Reference Network (ERN) EuroBloodNet. Stroke is one of the most devastating complications for children with sickle cell disease (SCD). For effective prevention of stroke risk, annual transcranial Doppler (TCD) according to a defined protocol is recommended for patients aged 2-16 years, with red blood cell transfusion therapy for those at risk. There is no information regarding screening for stroke risk and stroke prevention programs in Europe. METHODS: Seven SCD experts of five healthcare providers (HCPs) of ERN EuroBloodNet developed an online survey to assess the access to TCD screening and stroke prevention programs for children with SCD in Europe. RESULTS: Eighty-one experts in 77 HCPs from 16 European countries responded to 16 online questions. Thirty-two of 77 (51%) HCPs were EuroBloodNet reference centers, and 36% physicians reported not having a dedicated TCD/TCD imaging service for children with SCD. Only 30% of physicians provided estimates that all their patients received annual TCD according to the standard protocol due to lack of trained staff (43%), lack of TCD instruments (11%), refusal of patients due to logistical difficulties (22%), and lack of funds for dedicated staff or equipment (11%). CONCLUSIONS: This multinational European survey provides the first comprehensive picture of access to TCD screening and stroke prevention in European countries. Identifying the potential underlying causes of the lack of effective standardized screening, this survey also addresses possible dedicated actions to cover these needs.
ABSTRACT
BACKGROUND: Hemoglobinopathies, among which thalassemic syndromes (transfusion-dependent and non-transfusion dependent thalassemias) and sickle cell disease (SCD), are the most widespread monogenic diseases worldwide. Hemoglobinopathies are endemic and spread-out all-over Italy, as result of internal and external migration flows. Nowadays, the increase therapeutic options associated to the general aging of patients with hemoglobinopathies related to the improvement in clinical management, contribute to the abnormalities in kidney function going from blood and urine test alterations to chronic kidney disease and end stage renal disease. METHODS: Here, we carried out a revision of the literature as panel of recognized experts in hemoglobinopathies with the consultancy and the revision of two nephrologists on kidney alteration and kidney disease in patients with TDT, NTDT and SCD. This is part of the action of the Italian society for the study of thalassemia and hemoglobinopties (SITE). The purpose of this "good practice (GP)" is to provide recommendations for follow-up and therapy for the management of kidney alterations in patients with TDT, NTDT and SCD. The literature review covers the period 1.1.2016 to 31.12.2022. In consideration of the rarity of these diseases, the analysis was extended from 5 to 7 years. Moreover, in the absence of relevant scientific papers in the identified time frame, we referred to pivotal or population studies, when available. Finally, in the absence of evidence-based data from prospective and randomized trials, the authors had to refer to expert opinion (expert consensus) for many topics. RESULTS: We generated question and answer boxes to offer a friendly consultation, using color code strategy and focused answers. CONCLUSIONS: The present GP will help in improving the clinical management, and the quality of care of patients with hemoglobinopathies.
ABSTRACT
INTRODUCTION: Avascular necrosis (AVN) is a severe complication of sickle cell disease (SCD) and involves principally the femoral head. Few data exist about the prevalence of lesions in other segments. METHODS: In this cross-sectional study, 42 children (20 males and 22 females) underwent a magnetic resonance imaging (MRI) of the spine, upper arms, and femurs. The primary outcome was to define the prevalence and locations of bone infarcts. RESULTS: Forty-two patients completed the study; the total median age was 11.9 years (interquartile range = 9.5-13.9). Eleven patients (26.2%) were positive for altered bone findings for a total of 32 lesions. Most of the lesions were in the humerus 17 (53.1%), 11 (34.4%) in the femurs, and 4 (12.5%) in the vertebrae. The median number of vaso-occlusive crises (VOCs) was two and four for patients without and with bone lesions, respectively (p = .01). The annual rate of VOC is the best marker for the positive MRI (odds ratio = 82.6; p = .03), and it is correlated with the number of sites involved (p = .02). CONCLUSIONS: Our study highlights that the prevalence of skeletal lesions could be underestimated, and it provides the basis for clinical reasoning and tailored therapy in SCD children.
Subject(s)
Anemia, Sickle Cell , Male , Female , Humans , Child , Prevalence , Cross-Sectional Studies , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/epidemiology , Magnetic Resonance ImagingABSTRACT
Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT03397017.
ABSTRACT
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.
Subject(s)
COVID-19 , Iron Overload , Thalassemia , COVID-19/complications , Female , Hospitals , Humans , Iron Overload/etiology , Male , Oxygen , Registries , Thalassemia/complications , Thalassemia/therapySubject(s)
COVID-19/complications , Hemoglobinopathies/complications , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/mortality , Female , Hemoglobinopathies/epidemiology , Hemoglobinopathies/mortality , Humans , Italy/epidemiology , Male , Middle Aged , Prevalence , Risk Factors , SARS-CoV-2/isolation & purification , Thalassemia/complications , Thalassemia/epidemiology , Thalassemia/mortality , Young AdultABSTRACT
Manual erythroexchange (MEEX) was proven to be effective and safe in the management of sickle cell disease (SCD). The goal is to quickly reduce the percentage of hemoglobin S (HbS%). A national survey of the Italian Society for Thalassemia and Hemoglobinopathies (SITE) observed a great variability among MEEX protocols none of which were found to be predictive of the values of HbS% and hemoglobin (Hb) after the exchange. Two equations to estimate the HbS% and Hb values to be obtained after MEEX were developed based on the results of the MEEX procedures in place in the centers participating in the present study. A standard protocol was subsequently defined to evaluate the volumes to exchange to obtain the target values of HbS% and Hb. The protocol was tested in 261 MEEX performed in SCD patients followed in the 5 participating centers that belong to the Italian Hemoglobinopathy Comprehensive Care Network, with the support of the SITE. The results showed a correlation between the estimated and measured values of HbS% and Hb (Rp 0.95 and 0.65 respectively, p < 0.001). A negligible bias was found for the prediction of HbS% and a bias of 1 g/dl for Hb. From consecutive MEEX, a rate of increase of HbS% between two exchanges of around 0.4% per day (p < 0.001) was measured. This protocol was shown to be effective and safe, as all patients reached the target value of HbS%. All the MEEX procedures were carried out with single venous access. No adverse events or reactions such as hypotension or electrolyte imbalance were reported nor were any complaints concerning the procedures received from patients.
Subject(s)
Anemia, Sickle Cell/blood , Anemia, Sickle Cell/therapy , Blood Volume Determination/standards , Blood Volume/physiology , Erythrocyte Transfusion/standards , Hemoglobin, Sickle/metabolism , Adult , Anemia, Sickle Cell/epidemiology , Blood Volume Determination/methods , Erythrocyte Transfusion/methods , Female , Humans , Italy/epidemiology , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Reproducibility of Results , Young AdultABSTRACT
Sickle cell disease (SCD) is an inherited red blood cell disorder caused by a structural abnormality of hemoglobin called sickle hemoglobin (HbS). Clinical manifestations of SCD are mainly characterized by chronic hemolysis and acute vaso-occlusive crisis, which are responsible for severe acute and chronic organ damage. SCD is widespread in sub-Saharan Africa, in the Middle East, Indian subcontinent, and some Mediterranean regions. With voluntary population migrations, people harboring the HbS gene have spread globally. In 2006, the World Health Organization recognized hemoglobinopathies, including SCD, as a global public health problem and urged national health systems worldwide to design and establish programs for the prevention and management of SCD. Herein we describe the historical experience of the network of hemoglobinopathy centers and their approach to SCD in Italy, a country where hemoglobinopathies have a high prevalence and where SCD, associated with different genotypes including ß-thalassemia, is present in the native population.
Subject(s)
Anemia, Sickle Cell/prevention & control , Disease Management , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/metabolism , Hematologic Diseases/diagnosis , Hematologic Diseases/metabolism , Hematologic Diseases/prevention & control , Hemoglobinopathies/diagnosis , Hemoglobinopathies/metabolism , Hemoglobinopathies/prevention & control , Humans , Hydroxyurea/metabolism , Italy , Public HealthABSTRACT
We compared the safety and efficacy of alternating deferoxamine and deferiprone with that of deferoxamine monotherapy. Sixty transfusion-dependent thalassemia patients regularly treated with deferoxamine were randomized to continue deferoxamine alone or to receive an alternating therapy for one year. Both arms resulted in equivalent decreases of serum ferritin and liver iron concentration. There was no significant difference in the proportion of patients with adverse events in the two therapy groups although the nature of the adverse events differed according to the chelation regimen.