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Despite recent advances in understanding the pathophysiologic mechanisms behind the thalassemia intermedia (TI) phenotype, data on the effects of treatment are deficient. To provide such data, we evaluated 584 TI patients for the associations between patient and disease characteristics, treatment received, and the rate of complications. The most common disease-related complications were osteoporosis, extramedullary hematopoeisis (EMH), hypogonadism, and cholelithiasis, followed by thrombosis, pulmonary hypertension (PHT), abnormal liver function, and leg ulcers. Hypothyroidism, heart failure, and diabetes mellitus were less frequently observed. On multivariate analysis, older age and splenectomy were independently associated with an increased risk of most disease-related complications. Transfusion therapy was protective for thrombosis, EMH, PHT, heart failure, cholelithiasis, and leg ulcers. However, transfusion therapy was associated with an increased risk of endocrinopathy. Iron chelation therapy was in turn protective for endocrinopathy and PHT. Hydroxyurea treatment was associated with an increased risk of hypogonadism yet was protective for EMH, PHT, leg ulcers, hypothyroidism, and osteoporosis. Attention should be paid to the impact of age on complications in TI, and the beneficial role of splenectomy deserves revisiting. This study provides evidence that calls for prospective evaluation of the roles of transfusion, iron chelation, and hydroxyurea therapy in TI patients.

Introduction: Thalassemia intermedia (TI) is a heterogeneous genetic disease affecting the β-globin chain of the hemoglobin molecule resulting in a unique and wide clinical spectrum. The majority of TI patients are mildly anemic requiring merely occasional blood transfusions. Their mild anemia might be tolerable at a young age but over years it is proven to cause multiple system damage due to the chronic hypoxic and compensatory states. One of the systems affected, and the number one cause of mortality in this group, is the cardiovascular system. In this study we tried to assess echocardiographically the global left heart condition in TI patients and its relation to haematologic measurable variables (NT-proBNP, Ferritin, Hb, and HbF) as well as liver iron concentration (LIC). Subjects and Methods: A total of 74 patients were enrolled in our observational, case-series study having already met the conventional clinical and genetic criteria for diagnosing TI. LIC was measured by R2* MRI for all of the 74 patients who were then referred to an outpatient clinic for cardiac evaluation and echocardiographic testing between December 2006 and June 2007. Blood samples were also collected for measuring NT-proBNP levels in a random subgroup of 19 patients. Results: Of the 74 TI patients, 33 were male and 41 were female with a mean age of 26.54 (range 8–63) years and body surface area (BSA) of 1.54 (range 0.82–2.14) m2. Their mean hemoglobin was 8.43 (range 4.90–13.10) g/dl having a mean serum ferritin of 1023 (range 15–4140) ng/mL, a mean LIC of 9.00 (range 0.5–32.1) mg/g, and a mean NT-proBNP of 113.50 (range 16.42–371). The majority 59 (79.7%) had undergone splenectomy with only 11 (14.86%) maintained on iron chelation. Pulmonary hypertension (PHT) defined as peak systolic tricuspid gradient >30 mm Hg was present in 15 (38.5%) of our TI patients group excluding 35 patients with undetected tricuspid regurgitation. LV dilatation was significantly above the normal range in 48 (68.57%) patients. Left ventricular mass index (LVMI) was increased in 34(49.27%) patients; and all of them showed eccentric hypertrophy. The left ventricular ejection fraction (LVEF) was within normal range for most of the patients; only 3 had LVEF Conclusion: Although TI patients primarily develop PHT leading to right heart failure, our study has shown that many do exhibit sub-clinical left heart dysfunction (characterized by LV dilation and/or eccentric hypertrophy) as well. Knowing that iron overload correlates better with LIC than with ferritin in TI and after showing that LIC is negatively (but weakly) correlated with LVEF, iron overload might be a contributing factor to LV dysfunction similar to that encountered in TM. Finally; NT-proBNP is found to be negatively related only to hemoglobin level which adds to the poor prognosis of the profoundly anemic TI patients.