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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.)

Background:  Hypercoagulability in splenectomized patients with thalassemia intermedia (TI) has been extensively evaluated. However, clinical and laboratory characteristics of patients who eventually develop overt thromboembolic events (TEE) are poorly studied., Patients/methods:  Three Groups of TI patients (n=73 each) were retrospectively identified from a registry involving six centers across the Middle East and Italy: Group I, all splenectomized patients with a documented TEE; Group II, age- and sex-matched splenectomized patients without TEE; and Group III, age- and sex-matched non-splenectomized patients without TEE. Retrieved data included demographics, laboratory parameters, clinical complications, and received treatments that may influence TEE development, and reflected the period prior to TEE occurrence in Group I., Results:  The mean age of Group I patients at development of TEE was 33.1±11.7years, with a male to female ratio of 33:40. TEE were predominantly venous (95%) while four patients (5%) had documented stroke. Among studied parameters, Group I patients were more likely to have a nucleated red blood cell (NRBC) count ≥300×10(6) L(-1) , a platelet count ≥500×10(9)  L(-1) and evidence of pulmonary hypertension (PHT), or be transfusion naïve. The median time to thrombosis following splenectomy was 8years. Patients with an NRBC count ≥300×10(6) L(-1) , a platelet count ≥500×10(9) L(-1) , or who were transfusion naive also had a shorter time to thrombosis following splenectomy., Conclusion:  Splenectomized TI patients who will develop TEE may be identified early on by high NRBC and platelet counts, evidence of PHT, and transfusion naivety., (© 2010 International Society on Thrombosis and Haemostasis.)

Background: A high incidence of thrombotic events in thalassemia intermedia (TI) patients led to the identification of a hypercoagulable state. Brain involvement has not been widely studied in TI, although limited reports confirm a low incidence of overt stroke and high incidence of silent brain infarcts., Patients/methods: This was a prospective study conducted on 30 adult, splenectomized TI patients. Patients were screened for absence of neurological signs or symptoms, and stroke-related risk factors. Patient charts were reviewed for demographics, duration since splenectomy, and any history of transfusion therapy. Blood samples were obtained for complete blood counts and serum ferritin. Direct determination of liver iron concentration (LIC) was performed by R2 magnetic resonance imaging (MRI). Brain MRI was performed on all patients, looking for ischemic lesions and/or atrophy., Results: The mean age of patients was 32.1 +/- 11 years (range, 18-54 years), with a male to female ratio of 13:17. Eighteen patients (60%) had evidence of one or more white matter lesions (WMLs) on brain MRI, all involving the subcortical white matter. Fourteen patients had evidence of multiple WMLs, with a mean of 5 +/- 10 lesions (range, 2 to > 40 lesions). The vast majority of patients (94%) had small (< 0.5 cm) to medium (0.5-1.5 cm) WMLs, with only one patient showing evidence of a large (> 1.5 cm) WML. Eleven patients (37%) had mild cerebral atrophy. On multivariate analysis only age and transfusion history were independently and significantly associated with the occurrence of zero, single or multiple WMLs., Conclusion: WMLs and brain atrophy are a common finding in adult, splenectomized, TI patients. Increasing age and transfusion naivety are associated with a higher incidence and multiplicity of lesions.