Hydroxycarbamide (hydroxyurea or HU) has been shown to increase fetal hemoglobin (HbF) in patients with β-thalassemia intermedia (TI). The reported effects of HU in increasing the total hemoglobin (Hb) have been inconsistent. Studies of long-term therapy with HU in pediatric TI are rather uncommon. A retrospective observational study was carried out to evaluate the clinical responses to HU in Egyptian patients with β-TI. One hundred patients; children (n = 82, mean age 9.9 ± 4.1 years) and adults (n = 18) were studied for the mean Hb, HbF%, median serum ferritin, transfusion history, and splenic size before and after HU therapy (mean dose 20.0 ± 4.2 mg/kg/day, range 10-29 mg/kg/day) over a follow-up period 4 to 96 months (mean 35.4 ± 19.2 months). Molecular studies were also done for group of patients (n = 42). The overall response rate to HU was 79 %; 46 % were minor responders (with a reduction in transfusion rate by 50 % or more and/or an increase in their total hemoglobin level by 1-2 g/dl) and 33 % major responders (becoming transfusion-free and/or having an increase in total hemoglobin level by >2 g/dl). Mean hemoglobin increased among responders from 6.9 ± 0.9 g/dl to 8.3 ± 1.4 g/dl (p < 0.001). A significant rise in mean HbF (27.0 vs. 42.5 %; p < 0.011) and a decrease in median serum ferritin (800 vs. 644 ng/ml; p < 0.001) were also observed among responders (n = 45). Transfusions stopped in 44 % of pretreatment frequently transfused responders (n = 11/25). Splenic size decreased in 37 % of patients (n = 30/81). The predominant β-thalassemia mutation was 1-6 (T > C) in 32/42 (76 %) of studied patients; 28/32 were responders. Bivariate analysis showed no predictors of response as regards sex, pediatric and adult age, splenic status, or genotype. Hydroxycarbamide is a good therapeutic modality in the management of pediatric as in adult TI patients. It can minimize the need for blood transfusion, concomitant iron overload, and blood-born viral transmission especially in developing countries like Egypt.

TPO underproduction contributes to thrombocytopenia in children with cirrhosis; whereas in children with EHPVO, TPO production is unaffected and thrombocytopenia is secondary to hypersplenism. TPO receptor agonists may be useful to improve platelet counts in the former group.

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