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The effects of hydroxycarbamide on the plasma proteome of children with sickle cell anaemia
Author(s) -
Brewin John,
Tewari Sanjay,
Menzel Stephan,
Kirkham Fenella,
Inusa Baba,
Renney George,
Ward Malcolm,
Rees David C.
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15996
Subject(s) - haptoglobin , blood proteins , protein s , medicine , endocrinology , immunology , protein c
Summary 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) (89·8 vs. 81·4 g/l, P = 0·007) and HbF (6·7 vs. 15·3%, P < 0·001). Seventeen proteins were decreased on HC compared to controls by a factor of <0·77, and six proteins showed >1·3 increased concentration. HC use was associated with reduced haemolysis (lower α, β, δ globin chains, haptoglobin‐related protein, complement C9; higher haemopexin), reduced inflammation (lower α‐1‐acid glycoprotein, CD 5 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 = 0·603, P = 0·023). 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.