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Non-transfusion-dependent thalassaemias (NTDT) encompass a spectrum of anaemias rarely requiring blood transfusions. Increased iron absorption, driven by hepcidin suppression secondary to erythron expansion, initially causes intrahepatic iron overload. We examined iron metabolism biomarkers in 166 NTDT patients with β thalassaemia intermedia (n = 95), haemoglobin (Hb) E/β thalassaemia (n = 49) and Hb H syndromes (n = 22). Liver iron concentration (LIC), serum ferritin (SF), transferrin saturation (TfSat) and non-transferrin-bound iron (NTBI) were elevated and correlated across diagnostic subgroups. NTBI correlated with soluble transferrin receptor (sTfR), labile plasma iron (LPI) and nucleated red blood cells (NRBCs), with elevations generally confined to previously transfused patients. Splenectomised patients had higher NTBI, TfSat, NRBCs and SF relative to LIC, than non-splenectomised patients. LPI elevations were confined to patients with saturated transferrin. Erythron expansion biomarkers (sTfR, growth differentiation factor-15, NRBCs) correlated with each other and with iron overload biomarkers, particularly in Hb H patients. Plasma hepcidin was similar across subgroups, increased with >20 prior transfusions, and correlated inversely with TfSat, NTBI, LPI and NRBCs. Hepcidin/SF ratios were low, consistent with hepcidin suppression relative to iron overload. Increased NTBI and, by implication, risk of extra-hepatic iron distribution are more likely in previously transfused, splenectomised and iron-overloaded NTDT patients with TfSat >70%., (© 2016 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.)

Objective: To evaluate 30-day postoperative outcomes in laparoscopic (LS) versus open splenectomy (OS)., Summary Background Data: LS has generally been associated with lower rates of postoperative complications than OS. However, evidence mainly comes from small studies that failed to adjust for the confounding effects of the underlying indication or clinical condition that may have favored the use of one technique over the other., Methods: A retrospective cohort study of patients undergoing splenectomy in 2008 and 2009 using data from the American College of Surgeons National Surgical Quality Improvement Program database (n = 1781). Retrieved data included 30-day mortality and morbidity (cardiac, respiratory, central nervous system, renal, wound, sepsis, venous thromboembolism, and major bleeding outcomes), demographics, indication, and preoperative risk factors. We used multivariate logistic regression to assess the adjusted effect of the splenectomy technique on outcomes., Results: A total of 874 (49.1%) cases had LS and 907 (50.9%) had OS. After adjusting for all potential confounders including the indication and preoperative risk factors, LS was associated with decreased 30-day mortality [OR (odds ratio): 0.39, 95% CI: 0.18-0.84] and postoperative respiratory occurrences (OR: 0.46, 95% CI: 0.27-0.76), wound occurrences (OR: 0.37, 95% CI: 0.11-0.79), and sepsis (OR: 0.52, 95% CI: 0.26-0.89) when compared with OS. Patients who underwent LS also had a significantly shorter total length of hospital stay and were less likely to receive intraoperative transfusions compared with patients who underwent OS., Conclusions: LS is associated with more favorable postoperative outcomes than OS, irrespective of the indication for splenectomy or the patient's clinical status.

Covert brain infarction is an emerging concern in patients with β-thalassemia intermedia (TI). We have recently observed a high prevalence (60%) of silent brain infarction on brain magnetic resonance imaging (MRI) in 30 splenectomized adults with TI. In this work, we further evaluate cerebral involvement in the same 30 patients using fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scanning. The median age was 32 years (range, 18-54 years) with a male to female ratio of 13:17. Nineteen patients (63.3%) had evidence of decreased neuronal function on PET-CT. Involvement was mostly left sided, multiple, and most commonly in the temporal and parietal lobes. Elevated liver iron concentration, beyond 15 mg Fe/g dry weight, characterized patients with decreased neuronal function. The concordance rate between brain MRI and PET-CT for the detection of brain abnormality was only 36.7% (Kappa 0.056, P = 0.757), highlighting that both modalities reveal different types of brain pathology. Decreased neuronal function is a common finding in patients with TI and is associated with iron overload. Moreover, the addition of PET-CT to MRI identifies a greater proportion of TI patients with silent neuroimaging abnormalities.

Background:  Hypercoagulability and venous thromboembolism are common in patients with β-thalassemia intermedia (TI), especially in the splenectomized adult. Although arterial involvement is not commonly reported, we have recently observed a high prevalence (60%) of silent brain infarction on brain MRI in 30 splenectomized adults with TI. The pathophysiology of these white matter lesions remains unknown., Methods: In this prospective work, we evaluated magnetic resonance angiography (MRA) scans of the same cohort of 30 patients. Data collected were the presence or absence of vascular lesions, their locations, and severity. Correlations between MRA abnormality and patients/disease characteristics were evaluated. Comparisons between MRA and previous MRI findings were made., Results: Of 29 evaluable patients, 8 (27.6%) had evidence of arterial stenosis on MRA. The majority of lesions had mild narrowing and mostly involved the internal carotid artery. Five patients (17.2%) had evidence of aneurysms. Low total hemoglobin and high non-transferrin-bound iron levels independently characterized patients with evidence of stenosis on MRA. Among the 18 patients with silent brain infarction on MRI, three had evidence of stenosis on MRA with only one patient having lesions that could explain the silent infarcts., Conclusions: Cerebral vasculopathy is common in splenectomized adults with TI. However, large-vessel disease does not explain the occurrence of silent brain infarction. The combined use of MRA and MRI better identifies splenectomized TI adults with neuroimaging abnormalities., (© 2011 John Wiley & Sons A/S.)

Dear Editor, An association between chronic anemia and clinical sequelae in patients with non-transfusion-dependent -thalassemia (NTDT) has been established. (B) Probability of multiple morbidity development at various hemoglobin levels A multiple linear regression model was constructed with the number of morbidities as the outcome variable and hemoglobin level as the key explanatory variable while adjusting for age, splenectomy status, iron chelation status, and LIC. A total of 122 (81.3%) patients developed at least one morbidity, and 92 (61.3%) developed multiple morbidities (median number of morbidities: 2, range: 0-7) during the 10-year period. [Extracted from the article]

1 Kaplan-Meier curves for a morbidity-free survival and b multiple morbidity-free survival, as a function of baseline hemoglobin level Our data confirms the detrimental long-term effects of anemia on patient outcomes in NTDT. Serum ferritin level and morbidity risk in transfusion-independent patients with beta-thalassemia intermedia: the ORIENT study. Dear Editor, Chronic anemia is one of the key pathologic drivers in patients with non-transfusion-dependent -thalassemia (NTDT) and a marker for the severity of underlying ineffective erythropoiesis [[1]]. [Extracted from the article]

Efforts to optimize the management of patients with β-thalassemia major (TM) continue to expand. Evidence from biomedical research evaluating safe and careful processing measures of blood products, the efficacy and safety of oral iron chelators, and noninvasive techniques for the assessment of iron overload are translated into better patient outcomes. The construction of TM management guidelines facilitated the incorporation of such evidence into practice. However, as several aspects of the management of TM remain controversial or governed by resource availability, a concern regarding potential variations in recommendations made by the different guidelines becomes rational, especially for physicians treating TM patients outside countries where the guidelines were constructed. In this work, we overview currently available guidelines for the management of TM and explore apparent similarities and differences between them. The evaluated guidelines included the Thalassaemia International Federation, US, Canadian, UK, Italian and Australian guidelines. We noted a general consensus for most aspects of management, although some guidelines provided more comprehensive and contemporary recommendations than others. We did not identify differences warranting concern, although minor differences in iron overload assessment strategy and more notable variations in the recommendations for iron chelation therapy were observed. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Although life expectancy of thalassemia patients has markedly improved over the last few decades, patients still suffer from many complications of this congenital disease. The presence of a high incidence of thromboembolic events (TEE), mainly in β-thalassemia intermedia (β-TI), has led to the identification of a hypercoagulable state in these patients. In this review, the molecular and cellular mechanisms leading to hypercoagulability in thalassemia are highlighted, with a special focus on thalassemia intermedia being the group with the highest incidence of thrombotic events as compared to other types of thalassemia. Clinical experience and available clues on optimal management are also discussed. [ABSTRACT FROM AUTHOR]

Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with β thalassaemia intermedia (TI) has substantially increased over the past decade. The hallmark of disease process in patients with TI includes ineffective erythropoiesis, chronic haemolytic anaemia, and iron overload. There are a number of options currently available for managing patients with TI including splenectomy, transfusion therapy, iron chelation therapy, modulation of fetal haemoglobin production, and several other agents targeting specific clinical complications. Limited studies assessed the efficacy and safety of these modalities; hence, there are currently no clear guidelines for managing patients with TI. Until solid evidence-based guidelines are available, individualised treatment should be entertained. [ABSTRACT FROM AUTHOR]

Abstract: Transfusion-independent patients with β thalassemia intermedia (TI) experience a variety of clinical complications attributed to the underlying ineffective erythropoiesis and subsequent anemia, hemolysis, and iron overload. Growth differentiation factor-15 (GDF-15) was recently investigated as a marker of ineffective erythropoiesis in several anemias. In this work, we evaluated GDF-15 levels in 55 patients with TI. The mean GDF-15 level was 25,197.8±16,208.9pg/ml which is lower than values reported for patients with thalassemia major, yet considerably higher than those reported in patients with other congenital and acquired anemias. GDF-15 levels were significantly higher in splenectomized compared to non-splenectomized patients and correlated with anemia, markers of iron overload, and a pre-defined clinical severity score. Further studies are needed to determine the practical utility of GDF-15 measurement and its potential to reflect the severity of the clinical course in TI patients. [Copyright &y& Elsevier]

Abstract: Beta-thalassemia intermedia (TI) is associated with a variety of serious clinical complications that require proactive and comprehensive management. These include skeletal deformities and osteopenia, compensatory extramedullary hematopoiesis and tumor formation, progressive splenomegaly, a hypercoagulable state resulting in thromboembolic events and pulmonary hypertension, and increased gastrointestinal iron absorption that often results in nontransfusional iron overload and liver damage. Although TI is generally considered a non-transfusion-dependent thalassemia, transfusion therapy may be an important part of the comprehensive management of this disease. This review describes the current state of the art for medical management of TI, with particular focus on the roles of splenectomy, transfusion, and iron chelation therapy. [Copyright &y& Elsevier]

Abstract: Beta (β)-thalassemia is characterized by a hypercoagulable state and an increased risk of thrombosis, which can result in significant morbidity and mortality. The molecular and cellular mechanisms contributing to hypercoagulability are diverse and include chronic platelet activation, alteration of red blood cell membranes, abnormal expression of adhesion molecules on vascular endothelial cells, and dysregulation of hemostasis. Regular transfusions decrease the risk of thrombosis, whereas splenectomy significantly increases the risk. Splenectomized adults with non-transfusion-dependent thalassemia are also at high risk for ischemic brain damage. Strategies to lower the risk of thrombosis should be considered, including transfusion therapy to raise hemoglobin levels and avoidance or delay of splenectomy. [Copyright &y& Elsevier]