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.
The number of individuals with the sickle cell trait exceeds 300 million worldwide, making sickle cell disease one of the most common monogenetic diseases globally. Because of the high frequency of ...sickle cell disease, reproductive counseling is of crucial importance. In addition, unlike other carrier states, Sickle Cell Trait (SCT) seems to be a risk factor for several clinical complications, such as extreme exertional injury, chronic kidney disease, and complications during pregnancy and surgery. This expert panel believes that increasing knowledge about these clinical manifestations and their prevention and management can be a useful tool for all healthcare providers involved in this issue.
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.
ClinicalTrials.gov, identifier: NCT03397017.
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.
We considered 71 NTDT patients (30 females) enrolled in the Myocardial Iron Overload in Thalassemia Network and treated for >12 months with HU.
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.
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.
The aim of this multicenter study was to prospectively assess the predictive value of multiparametric cardiac magnetic resonance (CMR) for cardiovascular complications in sickle cell disease (SCD) ...patients. Among all patients with hemoglobinopathies consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network, we selected 102 SCD patients (34.38 ± 12.67 years, 49 females). Myocardial iron overload (MIO) was measured by the multislice multiecho T2* technique. Atrial dimensions and biventricular function parameters were quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect focal myocardial fibrosis. At baseline CMR, only two patients had significant MIO (global heart T2* < 20 ms). During a mean follow-up of 63.01 ± 24.95 months, 11 cardiovascular events (10.8%) were registered: 3 pulmonary hypertension, 2 supraventricular arrhythmias, 1 heart failure, 1 death for heart failure, 1 pulmonary embolism, 1 peripheral vascular disease, 1 transient ischemic attack, and 1 death after acute chest syndrome. In the multivariate analysis, the independent CMR predictors of cardiovascular events were left ventricular (LV) ejection fraction (hazard ratio-HR = 0.88;
p
= 0.025) and right ventricular (RV) mass index (HR = 1.09;
p
= 0.047). According to the receiver-operating characteristic curve analysis for adverse events, an LV ejection fraction < 58.9% and an RV mass index > 31 g/m
2
were optimal cut-off values. Reduced left ventricular ejection fraction and increased right ventricular mass index showed a significant prognostic value in patients with SCD. Our data seem to suggest that CMR may be added as a screening tool for identifying SCD patients at high risk for cardiopulmonary and vascular diseases.
Summary
In the last few decades, the life expectancy of regularly transfused β‐thalassaemia major (TM) patients has dramatically improved following the introduction of safe transfusion practices, ...iron chelation therapy, aggressive treatment of infections and improved management of cardiac complications. How such changes, especially those attributed to the introduction of iron chelation therapy, improved the survival of TM patients to approach those with β‐thalassaemia intermedia (TI) remains unknown. Three hundred and seventy‐nine patients with TM (n = 284, dead 40) and TI (n = 95, dead 13) were followed retrospectively since birth until 30 June 2015 or death. Kaplan‐Meir curves showed statistically significant differences in TM and TI survival (P < 0·0001) before the introduction of iron chelation in 1965, which were no longer apparent after that date (P = 0·086), reducing the Hazard Ratio of death in TM compared to TI from 6·8 95% confidence interval (CI) 2·6–17·5 before 1965 to 2·8 (95% CI 0·8–9·2). These findings suggest that, in the era of iron chelation therapy and improved survival for TM, the major‐intermedia dichotomy needs to be revisited alongside future directions in general management and prevention for both conditions.
Background: In developed countries, childhood mortality in sickle cell disease (SCD) is less than 5%, where the SCD morbidity and mortality burden has shifted to adults. As age increases, so do end ...organ complications like chronic pain. Environmental factors like health economics and genetic factors may influence such outcomes. Recent data from UK, showed higher than expected survival (ASH 2015) in the setting of a national health care system. The Hospital of Gela, Sicily has a well characterized Caucasian SCD population, which also has consistent access to health care via a nationalized system. We hypothesized that traditional disease severity markers including end organ damage, the rate of red blood cell (RBC) alloimmunization and opioid use would be lower in Sicily, compared to a modern US population of African ancestry with inconsistent access to healthcare.
Methods: 90 SCD patients in Sicily were followed for over 9 years (2006-2014) to identify clinical complications, alloimmunization rates and survival. Demographics and sickle and alpha globin genotypes were documented. In the US, 632 SCD patients (excluding those with SC) had the same parameters collected as part of the Bethesda Sickle Cell Cohort Study. Laboratory and clinical complications were compared between populations according to phenotype groups (SS/SB0 or SB+ thalassemia). Clinical manifestations included hospitalizations for pain per year, RBC alloimmunization, hydroxyurea prescription rate. Statistical analysis utilized univariate comparisons (t and Chi square tests).
Results: In Sicily, 51 patients had SS/SB0 and 28 SB+. All were of self-described Caucasian ancestry. No SC patients were identified in Sicily, therefore all comparisons were limited to SS/SB0 and SB+ thalassemia. Sicilian SS/SB0 patients were older than the US (p<0.0001), had lower AST (p=0.04) and creatinine (p=0.005), and higher HbF (p<0.0001). SB+ patients had similar characteristics (Table 1). Sixteen Sicilian patients (18%) died at a mean age of 53 years (range 31-77). As suggested by these survival data, SCD complications were less frequent for both SS/SB0 and SB+ groups in Sicily compared to the US (Table 2). More Sicilians were prescribed hydroxyurea, especially among those with SB+, although this was not a significant difference. The pain crisis hospitalizations per year was also higher in the US (p=0.008). Consistent with less frequent hospitalizations, only 4 of the Sicilian patients (3 SS/SB0, 1 SB+) were taking long acting opioids, compared to more frequent opioid use in the US. Finally, RBC alloimmunization, another surrogate measure for disease severity, was twice as common in SS/SB0 patients from the US (30%) as in Sicily (14%, p=0.01).
Conclusions: These data suggest that end organ complications, like chronic pain and alloimmunization, in self-described Caucasians with uniform access to health care in Sicily, are less common than in a US cohort of adults. These differences could be attributable to access to specialized care, genetic differences in the proportion of African ancestry or environmental factors like more frequent use of preventative therapies like hydroxyurea. RBC alloimmunization in Sicily is significantly lower than reported in the US , but is still higher than observed in thalassemics in Italy. Perhaps this could be explained a matched genetic background between blood donors and recipients in Sicily, as has been suggested as a strategy to reduce RBC alloimmunization in the US. Further studies comparing unique SCD populations from different geographic regions may be helpful to elucidate genetic or environmental risk factors for end organ complications and disease severity.
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No relevant conflicts of interest to declare.
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