The effects of hydroxycarbamide on the plasma proteome of children with sickle cell anaemia.

We investigated changes in the plasma proteome of children with sickle cell anaemia (SCA) associated with hydroxycarbamide (HC) use, to further characterize the actions of HC. Fifty-one children with SCA consented to take part in this study. Eighteen were taking HC at a median dose of 22 mg/kg, and 33 were not on HC. Plasma was analysed using an unbiased proteomic approach and a panel of 92 neurological biomarkers. HC was associated with increased haemoglobin (Hb) (89 center dot 8 vs. 81 center dot 4 g/l, P = 0 center dot 007) and HbF (6 center dot 7 vs. 15 center dot 3%, P < 0 center dot 001). Seventeen proteins were decreased on HC compared to controls by a factor of <0 center dot 77, and six proteins showed >1 center dot 3 increased concentration. HC use was associated with reduced haemolysis (lower alpha, beta, delta globin chains, haptoglobin-related protein, complement C9; higher haemopexin), reduced inflammation (lower alpha-1-acid glycoprotein, CD5 antigen-like protein, ceruloplasmin, factor XII, immunoglobulins, cysteine-rich secretory protein 3, vitamin D-binding protein) and decreased activation of coagulation (lower factor XII, carboxypeptidase B2, platelet basic protein). There was a significant correlation between the increase in HbF% on HC and haemopexin levels (r = 0 center dot 603, P = 0 center dot 023). This study demonstrated three ways in which HC may be beneficial in SCA, and identified novel proteins that may be useful to monitor therapeutic response.