Clinical Complications in Severe Pediatric Sickle Cell Disease and the Impact of Hydroxyurea

Background: More evidence of the safety and effectiveness of hydroxyurea (HU) in community-based cohorts of pediatric patients with sickle cell disease (SCD) are needed. The association of HU with organ-specific clinical complications and adverse events is examined herein.

Methods: Medicaid medical and pharmacy claims for the calendar years January 1996 through December 2006 were used to identify a cohort of children and adolescent patients (ages 17 and under) with a diagnosis of SCD (homozygous) who were treated with HU and developed disparate complications or adverse side effects. Of the 2,194 pediatric SCD patients identified, 175 (8%) were treated with HU. Incidence density matching (1 case: 2 controls) was used to select the control group on age, gender, ethnicity, time in the Medicaid data set, and baseline severity resulting in a total study cohort of 523 cases.

Results: Organ-specific complications were more likely in the HU-treated group compared to non-HU-treated group: cardiovascular complications (odds ratio [OR] = 3.15; confidence interval [CI] = 1.97-5.03); hepatic complications (OR 5.41; CI = 3.54-8.27); renal complications (OR 5.09; CI 3.37-7.67); and pulmonary complications (OR 4.07; CI 1.88-8.79). Many of these conditions began developing before HU was prescribed. Developing three or more complications was also more likely in the HU group (27.4% vs. 7.0%, P < 0.0001).

Conclusions: Extending previous findings to routine practice settings, HU is being administered to the most severely ill children with SCD, many of whom had already started to develop organ-specific complications, but it is not associated with development of serious adverse events.