Efficacy and safety of iron chelators in thalassemia and sickle cell disease: a multiple treatment comparison network meta-analysis and trial sequential analysis

Background: To compare the efficacy and safety of desferrioxamine (DFO), deferiprone (DFP), deferasirox (DFX) and silymarin in patients with either thalassemia or sickle cell disorder through network meta-analysis.

Methods: Electronic databases were searched for appropriate randomized clinical trials comparing iron chelators in patients with iron overload. Random effects model was used to generate direct, indirect and mixed treatment comparison pooled estimates for the following outcomes: serum ferritin, liver iron concentration (LIC), changes in serum ferritin, mortality, urine iron excretion, adverse events, neutropenia, agranulocytosis and number of patients withdrawing the chelating therapy.

Results: Thirty-two clinical trials were included in the meta-analysis. DFX/DFO was associated with better serum ferritin levels compared to DFO, DFX, DFO/Silymarin and DFP/DFO. DFX/DFO also lower LIC significantly compared to DFO. DFP/DFO was associated with higher LVEF, low risk of adverse events and reduced end of serum ferritin compared to DFO. Combination of silymarin with either DFP or DFX was observed with reduced end of treatment serum ferritin compared to using either of the drugs alone. DFP was observed with better effects in sickle cell disease. The strength of evidence was very low for most of the comparisons.

Conclusion: Relative estimates between the individual iron chelators have been established. However, this evidence should be considered preliminary and may change with the results of future head-to-head clinical trials.     

Relation of ferritin levels to pulmonary function in patients with thalassemia major and the acute effects of transfusion

We studied 36 patients (17 males and 19 females) with thalassemia major by performing pulmonary function testing (PFT), arterial blood gas analysis (ABG), as well as determining the serum ferritin level. In addition, 19 of these patients were transfused with two units of packed cells, and a repeat ABG and PFT were performed. Twenty-three patients had normal PFTs, eleven patients (30.6%) showed a restrictive pattern (significant decrease in both TLC and DLCO), and only two patients (5.6%) showed an obstructive pattern. A significant negative correlation was found between serum ferritin and restrictive parameters, DLCO and TLC (p = 0.01 and p = 0.03, respectively). This correlation was even stronger after transfusion. Controlling for age, ferritin was still negatively correlated with DLCO (p = 0.04), but no longer with TLC. There was no correlation between age and DLCO or age and TLC; however, there was a statistically significant negative correlation between age and FVC (p = 0.003). Analysis of patients who were transfused revealed a significant decrease in forced vital capacity (89 +/- 4% vs. 74 +/- 5% of predicted; p-value < 0.001) and in maximum midexpiratory flow rate (79 +/- 4% vs. 67 +/- 5% of predicted; p-value = 0.004). For patients older than 15 yr of age, there was a statistically significant decrease in FEV1/FVC (84 +/- 2 vs. 83 +/- 2%; p-value = 0.04). The ABGs showed no significant change post-transfusion. In this study, PFT findings in thalassemia major were restrictive and correlated with serum ferritin level. Transfusion had an acute effect on the obstructive parameters of PFT.     

The long-term efficacy in blood transfusions,hematologic parameter changes,and complications after splenectomy in patients with transfusion-dependent thalassemia

BackgroundA splenectomy can reduce transfusion requirements in patients with thalassemia. However, the role of a splenectomy remains controversial because its efficacy has not yet been fully determined and there are concerns over potential complications. The purpose of this study was to assess the efficacy, potential changes in hematologic parameters, and any complications associated with splenectomy.MethodsMedical records of 50 patients with transfusion-dependent thalassemia (TDT) who had undergone a splenectomy, along with those of 20 control subjects with intact spleens, were retrospectively reviewed.ResultsThe primary outcomes indicate the efficacy of a splenectomy in reducing red cell transfusions. Fifty TDT post-splenectomy patients were included in this study, of which 28 (56%) were female. The median age of all patients was 20.5 (18–28 years of age). Twenty-seven patients (54%) transformed from TDT to non-transfusion-dependent thalassemia (NTDT) after the splenectomy; 100% with Hb H disease, 58.3% with beta-thalassemia/Hb E disease, and 23.5% with homozygous beta-thalassemia. According to multivariable logistic regression analysis, Hb H disease (adjusted OR 55.23, 95% CI 1.35–22.8.10) and receiving a splenectomy at > ten years of age (adjusted OR 25.36, 95% CI 1.62–396.47) were associated with higher responses. The prevalence of pulmonary hypertension and thromboembolic events were similar between the splenectomy patients and non-splenectomy patients.ConclusionSplenectomy reduced transfusion requirements in TDT patients. The predictive factors as a response to a splenectomy included Hb H disease amongthose receiving a splenectomy at > ten years of age.     

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??Abstract??Congenital hemolytic anemia ??CHA?? is a hereditary disorder with main clinical presentation of hemolytic anemia??It is the most common disease of hereditary disorders in the world. According to the pathogenic mechanism??the disorders can be divided into three groups??abnormalities of the red cell membrane??red cell enzyme disorders and hemoglobinopathies.The most common CHA are hereditary spherocytosis??G-6-PD deficiency and the thalassemias??This article focuses on the management of these three types of diseases.     

Prevalence and genetic analysis of thalassemia in childbearing age population of Hainan,The Free Trade Island in Southern China

BackgroundHainan has one of the high incidences of thalassemia in China, but the epidemiological data in the whole province has not been reported yet. The objective of our study was to reveal the true prevalence and molecular mutation spectrum of thalassemia in the population of Hainan who are of childbearing age.MethodsWe screened 166,936 individuals from 19 cities and counties in Hainan by hematological parameters analysis, and further conducted genetic analysis for individuals whose MCV was less than 82fL.ResultsIn total, 21,619 (12.95%) subjects were diagnosed as thalassemia carriers or patients. The overall prevalence of α‐thalassemia, β‐thalassemia, and α+β‐thalassemia were 10.39%, 1.38%, and 1.18%, respectively. Eleven α‐thalassemia mutations and sixteen β‐thalassemia mutations were identified. The high‐frequent genotypes of α‐thalassemia were ‐α^3.7/αα (19.70%), ‐α^4.2/αα (19.39%), αα/‐‐^SEA (15.60%), α^WSα/αα (9.24%), and ‐α^3.7/‐α^4.2 (8.90%), and those of β‐thalassemia were β^{CD41/42(−TTCT)}/β^N (58.92%), β^−28(A>G)/β^N (16.05%), β^{IVS−Ⅱ−654(C>T)}/β^N (8.42%), β^CD71/72(+A)/β^N (6.03%), β^CD17(A>T)/β^N (5.47%), and β^{CD26 (GAG>AAG)}/β^N (2.69%). In addition, the frequencies and hematological profiles of many rare mutations of α‐ [Fusion, HKαα, αααanti^4.2, IVS‐II‐55 (T>G), IVS‐II‐119 (−G,+CTCGGCCC)] and β‐globin genes [−50 (G>A), IVS‐Ⅱ‐81 (C>T)] in Hainan were reported for the first time.ConclusionOur study revealed the high prevalence and extensive molecular spectrum of thalassemia in childbearing age population of Hainan, suggesting thalassemia in Hainan ranks second in prevalence among all regions in China. The findings will be useful for genetic counseling and prevention of thalassemia.     

Follow-up study of thyroid function in polytransfused thalassemic patients

The aim of our investigation was to evaluate thyroid function by a follow-up study in 45 polytransfused thalassemic patients, since endocrine abnormalities are frequent consequences of iron overload in thalassemia major. Significant changes of thyroid function have been revealed in the time elapsing the observation, despite unchanged haematological parameters; at the end of the present study five patients were affected by overt hypothyroidism and 15 patients by subclinical hypothyroidism. Ultrasound thyroid volume in 13 randomly selected patients was greatly reduced, while thyroid Magnetic Resonance Imaging (MRI) was not able to detect tissue alterations. Inversely, liver MRI was markedly reduced in 14 patients and negatively related to ferritine levels (P< 0.01). We conclude that polytransfused thalassemics are frequently affected by thyroid disfunction; haepatic haemosiderosis due to iron overload seems influence hormonal peripheral metabolism, although the patients display a moderate compliance with iron chelation therapy. Therefore, periodic thyroid investigation should be carried out in thalassemic subjects in order to detect patients who need hormone replacement therapy.     

贵州省三都水族人群β-地中海贫血发病情况调查

目的 了解贵州省水族人群β-地中海贫血的发病情况。方法 采用“红细胞休克一管定量法”测定红细胞脆性，醋酸纤维素薄膜电泳分离测定，一分钟碱变性法测定HbF。结果 在受检的1090人中，共检出β-地中海贫血携带者66例，检出率为6．06％，其中男性36例，女性30例，男女比例为1．2：1。结论 在贵州省三都地区水族人群中β-地中海贫血有较高的发生率，通过此次调查可使该人群对β-地中海贫血的严重危害性有所认识和引起有效的重视，这对开展优生优育，提高人口素质具有重要意义。