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While the number of participants experiencing adverse events, both sickle cell-related and otherwise, was similar in the two treatment arms, more subjects who were on hydroxyurea with phlebotomy experienced SAEs and SCA-SAEs at higher annualized rates than did subjects on the standard arm; http://www.selleck.cn/products/AZD0530.html these differences were higher when the transfusion overlap period in the alternative arm was excluded. In particular, almost a fourth of subjects who were on hydroxyurea and phlebotomy experienced a sickle cell pain SAE, whereas http://www.selleckchem.com/products/cx-5461.html of the same genotype [16]. According to the Cooperative Study of Sickle Cell Disease (CSSCD), the seminal natural history study, children with hemoglobin SS ages 10�C14 years and ages http://www.selleckchem.com/products/forskolin.html 15�C19 experienced 0.69 and 0.91 pain episodes per person-year, respectively [16]. Across treatments, our cohort appeared to have a similar incidence of pain episodes (0.90 events per person-year) to that seen in CSSCD. Whereas a painful event in CSSCD required a visit to a healthcare provider [17], for SWiTCH all pain events were collected, including, for example, historical self-reports of pain managed at home. Our analysis of predictors of SCA pain suggests that older age predicts the subjects' risk to have a sickle cell pain SAE. We did not find correlations with the alpha thalassemia status or beta globin haplotypes and pain. The study showed that an elevation of WBC predicted SCA pain events, especially in the hydroxyurea/phlebotomy group. White blood cells have been implicated in the vaso-occlusive event, possibly by contributing to leucocyte adhesion to the endothelium [18]. It is possible that the correlation of an elevated serum creatinine prior to a pain event may be related to dehydration; however, this information was not recorded. There were no treatment group differences in the incidence of other SCA-related SAEs such as acute chest syndrome and infections, although the number of events may be too small to reach a meaningful conclusion. Acute chest syndrome is commonly defined as the presence of a new pulmonary infiltrate on chest X-ray, usually associated with fever and other respiratory symptoms [19].