Several investigators have reported defective ristocetin-induced platelet aggregation (RIPA) in individuals whose red blood cells contain sickle haemoglobin, but the race of control subjects in these studies was not stated. Therefore, maximal amplitude of RIPA was examined in 75 normal whites and blacks, of 16 of whom had sickle trait defined by haemoglobin electrophoresis and sickle prep. Final ristocetin concentrations in platelet rich plasma were 1.1, 1.2 and 1.5 mg/ml. Mean aggregation at 1.1 mg/ml was significantly less in blacks (mean 31%) than in whites (mean 72%) (P less than 0.001). 60% of blacks but only 11% of whites had less than 50% RIPA at 1.1 mg/ml. RIPA was entirely absent in 19% of blacks. Differences in RIPA between black and white subjects were also present at ristocetin concentrations of 1.2 and 1.5 mg/ml but were less striking. RIPA in 25 children with homozygous sickle cell anaemia was similar to that in the normal AA and AS blacks. Differences in RIPA could not be explained by age, sex, presence of sickle haemoglobin, or medications. Addition of normal plasma or platelets did not correct reduced RIPA in seven blacks, and their plasma inhibited normal RIPA responses. Reduced platelet aggregation to low concentrations of ristocetin is a normal finding in many blacks, is not related to the presence of sickle haemoglobin, and appears to be due to a plasma inhibitor against RIPA.
Daptomycin is a lipopeptide antibiotic active against multidrug-resistant gram-positive organisms. Our search of the literature found no published pediatric pharmacokinetic data. We report the use of pharmacokinetic analysis of daptomycin in a 13-year-old boy with vancomycin-resistant Enterococcus faecium endocarditis. Pharamcokinetic parameters were found to be significantly different from published adult parameters, such as a faster elimination rate, shorter half-life, and increased clearance. These age-related differences in the pharmacokinetic profile of daptomycin have significant dosing implications. As the use of this drug for off-label indications and in pediatric populations increases, it is important for clinicians to better understand the drug's pharmacokinetic profile in these patient populations.
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