Athanassios Aessopos

Arterial Calcifications in β-Thalassemia

The purpose of this study was to define the incidence of arterial calcifications in patients with β-Thalassemia. β-thalassemia patients have been shown to present a high preva lence of angioid streaks and skin lesions characteristic of pseudoxanthoma elasticum (PXE). Given the fact that vascular involvement in the form of arterial calcifications is also a common manifestation of PXE, the authors investigated radiographically the presence of arterial calcifications in β-thalassemia patients. They studied 40 patients with β-thalassemia over 30 years of age. Forty healthy, age- and sex-matched subjects were chosen as a control group. Radiographs of the tibias were performed in order to disclose arterial calcifications. The occurrence of PXE skin lesions and of angioid streaks (AS) was also investigated. Arterial calcifications were detected in the posterior tibial artery in 22 (55%) β-thalassemia patients and in six (15%) controls (P<0.01 for the comparison). PXE skin lesions and AS were found in eight (20%) and 21 (52%) patients respectively. A total of 34 patients (85%) had at least one of the three lesions, namely, arterial calcifications, angioid streaks, and/or PXE-like skin lesions. Stepwise logistic regression analysis did not reveal prognostic value in independent variables such as transfusions, chelation therapy, pseudoxanthoma elasticum skin lesions and/or angioid streaks, diabetes, hemoglobin, serum ferritin, and uric acid. It was concluded that arterial calcifications are common in older β-thalassemia patients. This finding could be a manifestation of an acquired PXE syndrome associated with β-thalassemia, and consequently, vascular events complicating PXE should be expected in these patients.

The heart in transfusion dependent homozygous thalassaemia today – prediction, prevention and management

Cardiac disease remains the major cause of death in thalassaemia major. This review deals with the mechanisms involved in heart failure development, the peculiar clinical presentation of congestive heart failure and provides guidelines for diagnosis and management of the acute phase of cardiac failure. It emphasizes the need for intensive medical – cardiac care and aggressive iron chelating management as, with such approaches, today, the patients outcomes can be favourable in the long term. It covers advances in the assessment of cardiac iron overload with the use of magnetic resonance imaging and makes recommendations for preventing the onset of cardiac problems by tailoring iron chelation therapy appropriate to the degree of cardiac iron loading found.

Thalassemia intermedia today: should patients regularly receive transfusions?

BACKGROUND: β‐Thalassemia is an inherited hemoglobin disorder characterized by reduced synthesis of β‐globin chain. The severity of clinical course distinguishes this heterogeneous disease in two main subtypes: thalassemia major (TM) and thalassemia intermedia (TI). TI has a later clinical onset with a milder anemia that does not require transfusions at least during the first few years of life. The clinical picture of TI patients who have not received transfusions or have occasionally received transfusions is dominated by the consequences of chronic hemolytic anemia, tissue hypoxia, and their compensatory reactions, such as bone deformities and fractures, extramedullary hemopoiesis, spleen and liver enlargement, hypercoagulability, and pulmonary hypertension. These complications, especially the latter two, are getting more frequent and severe over the years. Nowadays, although TI patients have almost no changes in the course of the disease, well‐treated TM patients with regular transfusion‐chelation therapy showed suppression of the anemia‐related disorders in parallel to prolongation of life. The new oral iron chelators and the magnetic resonance imaging application for early detection of heart iron load are promising for further improvement on survival.

Angioid Streaks in Homozygous β Thalassemia

One hundred patients with homozygous β thalassemia (62 had β thalassemia major and 38 had β thalassemia intermedia) were examined by ophthalmoscopy for angioid streaks. Angioid streaks were found in 20 patients from both the β thalassemia major and β thalassemia intermedia groups (nine and 11 patients, respectively). A positive correlation was found between age and angioid streaks (P = .0017), as was a difference in the prevalence of angioid streaks between the two forms of the disease (P = .079). Additionally, a significant correlation was noted between chelating therapy and the prevalence of angioid streaks (P = .039). However, using multivariate analysis to correct for the effects of age, the correlation of angioid streaks with the form of disease disappeared, whereas the level of significance between chelation therapy and angioid streaks was reduced (P = .05). The high frequency of angioid streaks observed in patients with β thalassemia and the severe complications observed in one patient render a thorough ophthalmoscopic examination and follow-up of such patients necessary for both early diagnosis and possible therapeutic intervention.

Effect of deferiprone or deferoxamine on right ventricular function in thalassemia major patients with myocardial iron overload

BackgroundThalassaemia major (TM) patients need regular blood transfusions that lead to accumulation of iron and death from heart failure. Deferiprone has been reported to be superior to deferoxamine for the removal of cardiac iron and improvement in left ventricular (LV) function but little is known of their relative effects on the right ventricle (RV), which is being increasingly recognised as an important prognostic factor in cardiomyopathy. Therefore data from a prospective randomised controlled trial (RCT) comparing these chelators was retrospectively analysed to assess the RV responses to these drugs.MethodsIn the RCT, 61 TM patients were randomised to receive either deferiprone or deferoxamine monotherapy, and CMR scans for T2* and cardiac function were obtained. Data were re-analysed for RV volumes and function at baseline, and after 6 and 12 months of treatment.ResultsFrom baseline to 12 months, deferiprone reduced RV end systolic volume (ESV) from 37.7 to 34.2 mL (p = 0.008), whilst RV ejection fraction (EF) increased from 69.6 to 72.2% (p = 0.001). This was associated with a 27% increase in T2* (p < 0.001) and 3.1% increase in LVEF (p < 0.001). By contrast, deferoxamine showed no change in RVESV (38.1 to 39.1 mL, p = 0.38), or RVEF (70.0 to 69.9%, p = 0.93) whereas the T2* increased by 13% (p < 0.001), but with no change in LVEF (0.32%; p = 0.66). Analysis of between drugs treatment effects, showed significant improvements favouring deferiprone with a mean effect on RVESV of -1.82 mL (p = 0.014) and 1.16% for RVEF (p = 0.009). Using regression analysis the improvement in RVEF at 12 months was shown to be greater in patients with lower baseline EF values (p < 0.001), with a significant difference in RVEF of 3.5% favouring deferiprone over deferoxamine (p = 0.012).ConclusionIn this retrospective analysis of a prospective RCT, deferiprone monotherapy was superior to deferoxamine for improvement in RVEF and end-systolic volume. This improvement in the RV volumes and function may contribute to the improved cardiac outcomes seen with deferiprone.

Angioid streaks in sickle-thalassemia.

Angioid streaks have been described in a diverse group of diseases including hemoglobinopathies such as sickle cell anemia and beta-thalassemia. We investigated the prevalence of angioid streaks and pseudoxanthoma elasticum in the rare situation of patients who had compound heterozygous traits for hemoglobin S and beta-thalassemia. We examined 58 consecutive patients with sickle-thalassemia. Of these, 25 were men and 33 were women, and they ranged in age from 19 to 58 years (mean, 32.6 years). Angioid streaks were identified in six of 58 patients (10%), and of these three also displayed the cutaneous lesions of pseudoxanthoma elasticum, which were confirmed by skin biopsy. An expanded study on several relatives of the patients with angioid streaks failed to identify any similar cases. Statistical evaluation of the main hematologic and biochemical parameters in the patients with and without angioid streaks did not demonstrate any significant differences, except that the thalassemic component in all six patients with angioid streaks was beta(0) (that is, did not allow the synthesis of hemoglobin A). We conclude that angioid streaks and pseudoxanthoma elasticum skin lesions occur with an increased frequency in patients with sickle-thalassemia.

Intensive Chelation Therapy in β-Thalassemia and Possible Adverse Cardiac Effects of Desferrioxamine

Combination chelation therapy with desferrioxamine and deferiprone has recently been suggested as a more effective tissue iron—chelating treatment for transfusion-dependent β-thalassemia patients, although a standard dosage protocol has not yet been established. We describe a thalassemia major patient who had been treated with combination therapy with desferrioxamine and deferiprone and who was referred to us for faintness and dizziness associated with electrocardiographic ST-T changes and arrhythmia. A brief interruption of the treatment and a subsequent decrease in the drug doses caused the reversion of symptoms and findings. This response prompted us to speculate that a causal relationship existed between the observed abnormalities and the intensive chelation therapy. The possibility of this electrical instability as an adverse cardiac event occurring in the context of treatment with these chelating agents raises questions about the time of application of this therapy, the regimen dosages, and follow-up of such patients.

Correlation of echocardiography parameters with cardiac magnetic resonance imaging in transfusion-dependent thalassaemia major.

Background and objective: Heart iron load (cardiac Fe) can be indirectly quantified by cardiac magnetic resonance (CMR) T2*. CMR accessibility is limited, whereas echocardiography (Echo) is relatively inexpensive and readily available. The objective was to find Echo parameters that may be useful for predicting cardiac Fe. Design and methods: We compared a number of parameters derived from Echo to cardiac Fe in 142 thalassaemia major patients who had undergone a CMR study. Results: All patients with decreased left ventricular (LV) function had cardiac Fe. After removing those patients from the analysis, the total diameter index (Tdi) >5.57 cms/m2, left atrial diameter index >2.41 cm/m2, and the diastolic parameter E/A > 1.96 were highly specific (91.4%, 97.1% and 96.9% respectively) but had low sensitivity (31.8%, 20.45% and 21.8%) in predicting iron load. A right ventricular index >1.47 cm/m2, LV systolic index >2.26 cm/m2 or Tdi >6.26 cm/m2 discriminated between patients with no, or mild to moderate cardiac Fe from those with heavy load, with specificity of 91%, 98.5%, and 98.5%, respectively, but with low sensitivity. Interpretation and conclusions: Echo parameters for cardiac Fe prediction have restricted value, whereas CMR is essential to assess cardiac Fe. However, patients with decreased LV systolic function should be considered a priori as having cardiac Fe, and chelation therapy should be intensified. This also applies to patients who have the above‐described Echo criterion values, even if CMR is not available. Once a patient is found by CMR to have cardiac Fe, then the above Echo criterion values may be useful for ongoing monitoring.

Does Heterozygous β-Thalassemia Confer a Protection against Coronary Artery Disease?

Abstract: Six hundred and thirty‐eight patients who presented with clinical symptoms and/or electrocardiographic findings suggestive of stable angina pectoris were studied; they were also investigated by coronary arteriography. Hemoglobin electrophoresis was performed on all patients to detect the presence of the β‐thalassemia trait. Results were analyzed by logistic regression analysis to determine whether the latter confers any protective effect against advanced coronary artery disease (aCAD; defined as the presence of atheromas in coronary arteries, resulting in stenosis at least 70%). WeThe role of the currently accepted risk factors (smoking, hypertension, hypercholesterolemia, and diabetes) in developing aCAD were reconfirmed, while at the same time it was found that β‐thalassemia heterozygosity is associated with a reduced risk against aCAD (odds ratio 0.39, 95% confidence interval 0.16‐0.98). The lipoprotein and blood rheology profile of these individuals may be the underlying causes of this protective effect.

Hemothorax due to extramedullary erythropoietic masses

We describe a 27-year-old male patient suffering from beta-thalassemia intermedia who presented with a nontraumatic spontaneous hemothorax due to extramedullary hemopoietic foci. In reviewing the literature, four similar reports were found. The details of this unusual entity are discussed.