A two-year pilot trial of hydroxyurea in very young children with sickle-cell anemia.

OBJECTIVE: Hydroxyurea improves hematologic values and decreases vaso-occlusive complications in adults and children with sickle cell anemia (SCA), but has not been tested in infants before the onset of chronic organ dysfunction. We conducted a collaborative pilot trial of hydroxyurea in infants with SCA to assess its (1) feasibility of administration, (2) toxicity, (3) hematologic effects, and (4) effect on spleen function. STUDY DESIGN: Patients with hemoglobin (Hb) SS or Sbeta(0) thalassemia (n = 28, median age 15 months) received hydroxyurea for 2 years at 20 mg/kg/day. Hydroxyurea was temporarily discontinued for predefined toxicity. RESULTS: Seven patients exited the study early: five for noncompliance or refusal to continue, one for mild stroke, and one for fatal splenic sequestration. The predominant toxicity was transient neutropenia, which was usually associated with a viral-like illness. After 2 years of treatment, mean Hb level = 8.8 g/dL and Hb F = 20.3%, both higher than predicted age-specific levels. Radionuclide splenic uptake was absent in 47% of patients at study completion, compared with predicted functional asplenia in 80% of the patients. CONCLUSIONS: Hydroxyurea therapy for infants with SCA is feasible and well tolerated, has hematologic efficacy, and may delay functional asplenia. The potential for hydroxyurea to preserve organ function in SCA should be further evaluated.

Prevalence and clinical correlates of glomerulopathy in children with sickle cell disease.

OBJECTIVES: Glomerular disease and renal failure cause substantial morbidity for patients with sickle cell disease (SCD). Proteinuria is an early manifestation of sickle nephropathy, but the prevalence of proteinuria and its clinical correlations in children with SCD are unknown. STUDY DESIGN: Data were collected prospectively on children with SCD for 10 years including physical measurements, laboratory test results, and clinical complications. Persistent proteinuria was defined as > or =1+ protein on urinalysis for at least 6 months. The glomerular filtration rate was estimated with serum creatinine concentration and height. Proteinuria was correlated with other variables by chi(2) analysis. RESULTS: Proteinuria occurred in 20 of 442 pediatric patients including 15 (6.2%) with sickle cell anemia. Proteinuria increased with age, affecting 12% of older teenagers with sickle cell anemia. Proteinuria was significantly associated with lower hemoglobin concentration, higher mean corpuscular volume, and higher leukocyte count. For children of some ages, proteinuria was associated with complications including stroke, acute chest syndrome, cholelithiasis, and hospitalizations. Glomerular filtration rate hyperfiltration occurred early in life, followed by normalization. CONCLUSIONS: Sickle nephropathy, manifested as persistent proteinuria, begins early in life, occurs in all forms of SCD, and is associated with severity of disease. Early detection of proteinuria may allow therapy to prevent progressive renal insufficiency.

Glucose-6-phosphate dehydrogenase Durham: a de novo mutation associated with chronic hemolytic anemia.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzyme defect. We report a new variant, G6PD Durham713G, that is associated with chronic nonspherocytic hemolytic anemia. The G6PD Durham713G variant has a unique biochemical and enzymatic profile and a novel A-->G substitution mutation at nucleotide 713, changing lysine to arginine at amino acid 238. This mutation was not found in the mother of our patient, indicating that G6PD Durham713G resulted from a de novo mutation.

High-dose oral dexamethasone therapy for chronic childhood idiopathic thrombocytopenic purpura.

Because high-dose oral dexamethasone therapy has been reported to be effective for adults with idiopathic thrombocytopenic purpura, we assessed the short-term efficacy and toxicity of dexamethasone in seven children with chronic or refractory idiopathic thrombocytopenic purpura. Dexamethasone therapy was effective and well tolerated; further long-term studies are warranted.

Pitfalls in newborn hemoglobinopathy screening: failure to detect beta(+)-thalassemia.

Although universal newborn screening can reliably identify all infants with sickle cell hemoglobinopathies, the initial screening result must not be considered the definitive diagnosis. We describe 23 infants whose screening phenotype was FS or FC but whose true phenotype included hemoglobin A, establishing a definitive diagnosis of hemoglobin S or hemoglobin C in combination with beta(+)-thalassemia. Higher than expected hemoglobin concentrations or lower than expected mean erythrocyte volumes should suggest concurrent beta(+)-thalassemia.

Hemoglobin C disease in infancy and childhood.

We reviewed the clinical course, physical findings, and hematologic values in 16 pediatric patients with hemoglobin C disease, all but one identified by a newborn hemoglobinopathy screening program. The patients had a few symptoms or physical findings. Height and weight percentiles were normal. Patients typically had a mild hemolytic anemia characterized by microcytosis and target cells.

Gallbladder sludge in children with sickle cell disease.

Ultrasonographic records of 75 children with sickle cell disease and hepatobiliary symptoms were reviewed. Seventeen had gallbladder sludge, nine with concurrent stones and eight with sludge alone. Because all the children eventually had gallstones, we recommend that elective cholecystectomy be performed on patients with gallbladder sludge.

Laparoscopic cholecystectomy in young patients with sickle hemoglobinopathies.

Nine young patients with sickle hemoglobinopathies successfully underwent laparoscopic cholecystectomy; no complications resulted from the procedure. The mean postoperative hospital stay was 1.6 days. This technique appears to be a safe and efficacious procedure in children with sickle hemoglobinopathies who require cholecystectomy for cholelithiasis.

Long-term management of splenic sequestration in children with sickle cell disease.

We describe our experience with 23 children with sickle cell disease and splenic sequestration crisis, emphasizing our management approaches and the patients' subsequent clinical courses. Our data illustrate that sequestration crisis may occur despite a reduction in hemoglobin S concentration to less than 30% of the total hemoglobin mass. In addition, the risk of recurrent splenic sequestration was similar for patients who received transfusion therapy and for those who were simply observed. We conclude that a short-term transfusion program to prevent recurrent splenic sequestration is of limited benefit.