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CONTEXT. Hydroxyurea is the only approved medication for the treatment of sickle cell disease in adults; there are no approved drugs for children. OBJECTIVE. Our goal was to synthesize the published literature on the efficacy, effectiveness, and toxicity of hydroxyurea in children with sickle cell disease. METHODS. Medline, Embase, TOXLine, and the Cumulative Index to Nursing and Allied Health Literature through June 2007 were used as data sources. We selected randomized trials, observational studies, and case reports (English language only) that evaluated the efficacy and toxicity of hydroxyurea in children with sickle cell disease. Two reviewers abstracted data sequentially on study design, patient characteristics, and outcomes and assessed study quality independently. RESULTS. We included 26 articles describing 1 randomized, controlled trial, 22 observational studies (11 with overlapping participants), and 3 case reports. Almost all study participants had sickle cell anemia. Fetal hemoglobin levels increased from 5%–10% to 15%–20% on hydroxyurea. Hemoglobin concentration increased modestly (∼1 g/L) but significantly across studies. The rate of hospitalization decreased in the single randomized, controlled trial and 5 observational studies by 56% to 87%, whereas the frequency of pain crisis decreased in 3 of 4 pediatric studies. New and recurrent neurologic events were decreased in 3 observational studies of hydroxyurea compared with historical controls. Common adverse events were reversible mild-to-moderate neutropenia, mild thrombocytopenia, severe anemia, rash or nail changes (10%), and headache (5%). Severe adverse events were rare and not clearly attributable to hydroxyurea. CONCLUSIONS. Hydroxyurea reduces hospitalization and increases total and fetal hemoglobin levels in children with severe sickle cell anemia. There was inadequate evidence to assess the efficacy of hydroxyurea in other groups. The small number of children in long-term studies limits conclusions about late toxicities.

OBJECTIVES. Primary hemorrhagic stroke is an uncommon complication of sickle cell disease, with reported mortality rates of 24% to 65%. Most reported cases are in adults; little is known about its occurrence in children. Proposed risk factors include previous ischemic stroke, aneurysms, low steady-state hemoglobin, high steady-state leukocyte count, acute chest syndrome, and hypertransfusion. We performed a retrospective case-control study to evaluate risk and prognostic factors for primary hemorrhagic stroke among children with sickle cell disease. PATIENTS AND METHODS. Case subjects (sickle cell disease and primary hemorrhagic stroke) and control subjects (sickle cell disease and ischemic stroke) were identified at 2 children’s hospitals from January 1979 to December 2004 by reviewing divisional records and the discharge databases. RESULTS. We identified 15 case subjects (mean age: 10.4 ± 1.3 years) and 29 control subjects (mean age: 5.2 ± 0.4 years). An increased risk of hemorrhagic stroke was associated with a history of hypertension and recent (in the last 14 days) transfusion, treatment with corticosteroids, and possibly nonsteroidal antiinflammatory drugs. Average blood pressures at well visits (adjusted for age and gender) were similar between the 2 groups, suggesting that hypertension was intermittent CONCLUSIONS. In this group of children with sickle cell disease, hemorrhagic stroke was associated with a history of hypertension or antecedent events including transfusion or treatment with corticosteroids. Improved understanding of risk and prognostic factors, especially those that are modifiable, may help prevent this devastating complication in children with sickle cell disease.

First and secondhand (SHS) smoke exposure are associated with increased morbidity in sickle cell disease (SCD). Likewise, asthma and pulmonary function abnormalities such as lower airway obstruction and airway hyper responsiveness are associated with increased SCD morbidity and mortality. Abnormalities often occur in the absence of atopy, and environmental factors may play an important role. We hypothesized that smoke exposure (first or secondhand) is associated with pulmonary function abnormalities and asthma independent of atopic status. We present …

The observation of Ross et al provides a serendipitous insight into the possible effects of transfusion and subarachnoid hemorrhage (SAH) on cerebral blood flow velocities (CBFVs) in children with sickle cell disease (SCD). Their patient, an 8-year-old girl with hemoglobin SS, had abnormally high transcranial Doppler (TCD) velocities of the bilateral middle cerebral arteries (204 cm/second on the left and 220 cm/second on the right) before blood transfusion for acute chest syndrome. CBFV is inversely proportional to hematocrit,1 so worsening anemia may have been partially responsible for the elevation. Increases in metabolic requirements of the brain, such as with a fever or hypoxia, also increase CBFV as the brain increases blood flow to meet metabolic demands.2 However, although not seen on angiography, the degree of elevation suggests that other processes, such as fixed stenosis or vasoconstriction, may have also contributed. Elevated velocity was associated with hemorrhagic stroke …