Thalassemia Major Cases Research Articles

Pulmonary Hypertension in β‐Thalassemia

Abstract: Cardiac involvement represents the leading cause of mortality in both forms of β‐thalassemia, namely, thalassemia major (TM) and thalassemia intermedia (TI), and pulmonary hypertension (PHT) is part of the cardiopulmonary complications of the disease. PHT was initially documented in a small group of TI patients with right heart failure. In a subsequent study of a large 110‐patient series, aged 32.5 ± 11.4 years, age‐related PHT was encountered in nearly 60% of cases, having caused right heart failure in six of them; interestingly, all patients had preserved left ventricular systolic function. Conflicted evidence, however, existed with respect to the development of PHT in heterogeneously treated and young TM populations. To resolve this discrepancy, a recent study compared cardiac disease between two large aged‐matched groups of TM (n= 131) and TI (n= 74) patients, both treated uniformly in the currently accepted manner (regular transfusion and chelation therapy in TM, absence of any particular treatment in TI); well‐treated TM patients, in contrast to TI patients, did not develop PHT, while systolic left ventricular dysfunction was present only in TM cases. PHT in β‐thalassemia results from a rather complex pathophysiology, in which chronic tissue hypoxia seems to hold a key role. Although both forms of the disease share a common molecular background, the diverse severity of the genetic defect and of the resulting clinical phenotype require a different therapeutic approach. Regular lifelong therapy in TM patients eliminates chronic hypoxia, thereby preventing PHT, whereas the absence of systematic treatment in TI leads to a cascade of reactions that compensate for chronic anemia, but at the same time allow the development of PHT.

Antihistone and Other Autoantibodies in β-Thalassemia major Patients Receiving Iron Chelators

This study was designed to find out the incidence of various autoantibodies in patients receiving iron chelators. Two groups were studied for comparison. One group consisted of thalassemia major cases on deferiprone (L1) and the second group were those receiving desferrioxamine therapy. Various autoantibodies such as antihistone antibodies and its subfractions H1, H2A-H4B, H2B, H3, ANF, anti-dsDNA, anti-nRNP, anti-Sm, ANCA and rheumatoid factor were tested. Out of 180 patients 50 patients (27.8%) were on desferrioxamine therapy, and 60 patients (33.3%) were taking deferiprone, whereas 70 patients (38.9%) were untreated. Antihistone antibodies were found in 30% of patients receiving deferiprone and 48% in the desferrioxamine group, respectively, as compared to control thalassemics (14.3%). Also, the levels of antihistone antibody were significantly elevated in the chelator groups as compared to controls. When antibodies to subfractions of the histone molecule were studied, it was observed that antibodies to H1 were most commonly seen and IgG was the major immunoglobulin subclass. Anti-dsDNA and anti-Sm antibodies, which are the diagnostic markers of idiopathic SLE, were absent in these patients. β-Thalassemia major patients on iron chelators such as desferrioxamine and deferiprone show changes in their autoimmune profile suggestive of some humoral immune alterations.