Anna Spasiano

Dispersion of repolarization and beta-thalassemia major: the prognostic role of QT and JT dispersion for identifying the high-risk patients for sudden death

Background:u2002 Patients with beta‐thalassemia major (β‐TM) are at increased risk for sudden cardiac death (SCD). Heterogeneity of ventricular repolarization is considered to provide an electrophysiological substrate for malignant arrhythmias. QT dispersion (QTc‐D) and JT dispersion (JTc‐D) are electrocardiographic parameters indicative of heterogeneity of ventricular repolarization. The aim of our study was to evaluate the heterogeneity of ventricular repolarization in patients with beta‐thalassemia and to test the hypothesis that an abnormal QTc and JTc dispersion may predict SCD in this population.

Early electrocardiographic evaluation of atrial fibrillation risk in beta-thalassemia major patients

Although previous studies have documented a variety of electrocardiogram abnormalities in beta-thalassemia major (β-TM), little is known about P-wave dispersion (PD), an independent risk factor for development of atrial fibrillation. The aim of our study was to evaluate PD in β-TM patients with conserved systolic and diastolic functions. The study involved 40 β-TM patients (age 37.5 ± 10.2; 33 M) and 40 healthy subjects used as controls, matched for age and gender. PD was carefully measured using a 12-lead electrocardiogram. Cardiac iron levels were measured by cardiac magnetic resonance T2 star (CMR T2*) imaging. Comparing to the healthy control group, β-TM group presented increased values of the PD (40.1 ± 12.9 vs. 24 ± 7 ms; P < 0.004) and decreased CMR T2* imaging (29 ± 15 vs. 55 ± 13 ms; P = 0.03). We found a significant correlation between PD and CMR T2* values. Our study showed a significant increase of PD in β-TM patients with conserved systolic and diastolic cardiac functions. Our results indicate that PD is correlated to myocardial iron deposit, as assessed by CMR T2* imaging.

Atrial Fibrillation and Beta Thalassemia Major: The Predictive Role of the 12-lead Electrocardiogram Analysis

Background Paroxysmal atrial tachyarrhythmias frequently occur in beta-thalassemia major (β-TM) patients.The aim of our study was to investigate the role of maximum P-wave duration (P max) and dispersion (PD), calculated trough a new manually performed measurement with the use of computer software from all 12-ECG-leads,as predictors of atrial-fibrillation (AF) in β-TM patients with conserved systolic or diastolic cardiac function during a twelve-months follow-up. Materials and Methods 50 β-TM-patients (age38.4±10.1; 38M) and 50-healthy subjects used as controls, matched for age and gender, were studied for the occurrence of atrial arrhythmias during a 1-year follow-up, through ECG-Holter-monitoring performed every three months. The β-TM-patients were divided into two groups according to number and complexity of premature-supraventricular-complexes at the Holter-Monitoring (Group1: <30/h and no repetitive forms, n:35; Group2: >30/h or couplets, or run of supraventricular tachycardia and AF, n:15). Results Compared to the healthy control-group, β-TM patients presented increased P-max (107.5± 21.2 vs 92.1±11ms, P=0.03) and PD-values (41.2±13 vs 25.1±5 ms,P=0.03). In the β-TM population, the Group2 showed a statistically significant increase in PD (42.8±8.6 vs 33.2±6.5ms, P<0.001) and P-max (118.1±8.7 vs 103.1±7.5ms, P<0.001) compared to the Group1. Seven β-TM patients who showed paroxysmal AF during this study had significantly increased P-max and PD than the other patients of the Group2. Moreover, P-max (OR:2.01; CI:1.12-3.59; P=0.01) and PD (OR=2.06;CI:1.17-3.64;P=0.01) demonstrated a statistically significant association with the occurrence of paroxysmal AF,P min was not associated with AF-risk (OR=0.99; CI:0.25-3.40; P=0.9) in β-TM-patients. A cut-off value of 111ms for P-max had a sensitivity of 80% and a specificity of 87%, a cut-off value of 35.5ms for PD had a sensitivity of 90% and a specificity of 85% in identifying β-TM patients at risk for AF. Conclusion Our results indicate that P-max and PD are useful electrocardiographic markers for identifying the β-TM-high-risk patients for AF onset, even when the cardiac function is conserved.

A useful relationship between the presence of extramedullary erythropoeisis and the level of the soluble form of the transferrin receptor in a large cohort of adult patients with thalassemia intermedia: a prospective study

In thalassemia intermedia (TI), the increase in bone marrow hemopoietic activity frequently leads to extramedullary erythropoeisis (EMH), but its relationship with the soluble form of transferrin receptor (sTfR) which fully reflects the marrow erythropoietic activity, has not yet been explored. From January 2007 to December 2010, all TI patients attending at our center were prospectively enrolled to undergo sTfR assay and MRI or CT (if claustrophobic) scan evaluation for the presence of paraspinal EMH. A total of 59 patients with TI were studied; EMH involved 23 (39%) patients; overall, the concentration of sTfR varied from 2.6 to 20.6 (meanu2009=u20098.7) mg/L, but in splenectomized group and in unsplenectomized group, it varied from 4.2 to 17.8 (meanu2009±u2009SDu2009=u20099.86u2009±u20093.33) mg/L and from 2.6 to 20.6 (meanu2009±u2009SDu2009=u20097.25u2009±u20093.9) mg/L, respectively with a statistically significant intergroup difference (pu2009<u20090.01). The cutoff point at 8.6xa0mg/L using the ROC curve showed a sensitivity of 78.3% and a specificity of 72.2%, in predicting EMH but, in unsplenectomized subgroup, they raised to 100% and 90.9%, respectively. These data showed that in TI the level of sTfR could represent a predictive factor of EMH particularly in patients with spleen.

Hypocholesterolemia in adult patients with thalassemia: a link with the severity of genotype in thalassemia intermedia patients.

Objectives:u2002 Hypocholesterolemia has been previously described in patients affected by thalassemia. In this study we retrospectively evaluated the cholesterol level in two groups of patients affected by either thalassemia major (TM) or thalassemia intermedia (TI), with the aim of establishing factors correlated to hypocholesterolemia within both populations.

Combined chelation therapy in thalassemia major with deferiprone and desferrioxamine: a retrospective study

Objectives: The benefits of combined chelation therapy with daily deferiprone (DFP) and subcutaneous desferrioxamine (DFO) have been widely reported in literature. We retrospectively evaluated the efficacy of different schedules of combined chelation therapy and the incidence of adverse events. Methods: We evaluated 36 patients affected by thalassemia major treated with combined chelation therapy. Patients were subdivided into four treatment arms according to severity of iron overload and previous onset of adverse events to DFP therapy: Group 1 (13 pts) DFP 75u2003mg/kg per d plus DFO (25–35u2003mg/kg per d for 5u2003d); Group 2 (6 pts) DFP 50u2003mg/kg per d plus DFO (25–35u2003mg/kg for 5u2003d), Group 3 (10 pts) DFP 75u2003mg/kg per d plus DFO (25–35u2003mg/kg for 3u2003d), and Group 4 (7 pts) DFP 50u2003mg/kg per d plus DFO (25–35u2003mg/kg for 3u2003d). Change in serum ferritin level was evaluated in all patients. Results: Overall, ferritin decreased from 2592u2003±u20031701 to 899u2003±u2003833u2003ng/mL (Pu2003<u20030.001). All treatments were able to reduce ferritin levels, but in patients of group 1 and group 2 the highest mean decrease in serum ferritin level and the greatest improvement in liver iron concentration (LIC) and in T2* values were observed. Conclusions: This study showed that the administration of DFO for 5u2003d a wk in combination with daily administration of DFP at 75u2003mg/Kg seemed to be the most efficacy and rapid method for reducing iron overload at liver and heart level. Furthermore, the use of different schedules of combined DFO and DFP administration was not associated with different incidence of adverse effects between the groups.

Splenectomy is a risk factor for developing hyperuricemia and nephrolithiasis in patients with thalassemia intermedia: a retrospective study.

Few data are available on the prevalence and the risk factors for the presence of kidney stones and hyperuricemia in patients with thalassemia intermedia. We retrospectively reviewed the charts and radiological studies of 89 patients with thalassemia intermedia followed at our clinic with routine biochemical examination and radiological imaging of the urinary tract. Renal calculi were identified in 11 patients (12%) and 22 patients (25%) were under uricosuric treatment for hyperucemia. The prevalence of nephrolithiasis increased with age but not in a statistically significant manner. Major risk factors for renal stone formation were splenectomy (in 91% of the cases) and higher number of erythroblasts. Patients with renal stones had higher mean creatinine level and lower GFR value with respect to those observed in patients not affected. Our data suggest that splenectomy, by further increasing erythrocyte turnover and number, may be directly involved in the pathogenesis of hyperuricemia and nephrolithiasis observed in thalassemia intermedia patients.

Distinguishing Visceral Leishmaniasis from Intolerance to Pegylated Interferon-α in a Thalassemic Splenectomized Patient Treated for Chronic Hepatitis C

A 37-year-old splenectomized man affected by beta-thalassemia and chronic hepatitis, recently treated with pegylated interferon-alpha (Peg-IFN), was admitted because of elevated fever lasting 3 months and unresponsiveness to broad-spectrum antibiotics. Laboratory studies showed white blood cell and platelet counts within the normal range but lower than observed before Peg-IFN treatment and an elevated erythrocyte sedimentation rate. The blood transfusion rate was reported to be increased compared with the period preceding Peg-IFN treatment. A diagnosis of visceral leishmaniasis (VL) was made after Leishmania amastigotes were identified from Giemsa-stained smears of bone marrow aspirates. Cure occurred after liposomal amphotericin B was administered. Symptoms of VL may be difficult to distinguish from the manifestations of Peg-IFN intolerance. We suggest that VL must be suspected in any immunodepressed patient with an unexplained fever and a history of exposure in an endemic area.

The impact of previous or concomitant IFN therapy on deferiprone-induced agranulocytosis and neutropenia: a retrospective study.

Objective: Although IFN therapy is known to cause neutropenia, data on the risk of deferiprone (DFP)-induced haematological complications in patients receiving IFN are lacking. Research design and methods: This was a retrospective single-centre study to assess the association between exposure to IFN for hepatitis C virus treatment and haematological side effects of DFP therapy in patients with thalassemia major and intermedia using a large database spanning 2001 – 2008. During observation time, a total of 66 patients, including 63 affected by thalassemia major and 3 by thalassemia intermedia, were treated with chelation DFP-based regimens. A subset of 25 patients was treated at least for 3 months also with IFN (6 were cotreated and 19 were pretreated). Results: Overall, the incidence of neutropenia and agranulocytosis was 9.83 and 1.14/100 patient/year, respectively. Receipt of IFN was significantly associated with increased risk of haematological complications of DFP therapy: among patients receiving IFN, 48 and 12% experienced at least one episode of neutropenia and agranulocytosis, respectively. Conclusions: These results suggest that IFN therapy may increase the risk of complications of DFP-based iron chelation therapy in patients with thalassemia. Further research is needed to assess whether the association observed in this retrospective single-centre observational study is due to IFN or other factors.

Hepatitis C virus distribution and clearance following interferon-monotherapy among thalassaemia major and intermedia patients.

Additional Supporting Information may be found in the online version of this article: Table SI. Complete Steady state plasma amino acid concentrations in SCA patients who subsequently died compared to age and sex matched SCA patients who were alive as of 1st July 2009. Table SII. Available laboratory markers of hemolysis and liver and kidney function in patients at enrollment into the cohort (steady-state) and at the time of amino acid steady-state sample collection. Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.