期刊
ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION
卷 88, 期 2, 页码 F113-F118出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/fn.88.2.F113
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Objective: To compare the pharmacokinetics and efficacy of oral versus intravenous mixed micellar vitamin K prophylaxis in infants with cholestatic liver disease, a known risk factor for vitamin K deficiency bleeding. Design: Prospective randomised controlled study. Setting: Paediatric Liver Unit. Patients: Forty four infants less than 6 months of age with conjugated hyperbilirubinaemia. Main outcome measures: Serum concentrations of vitamin K-1 and undercarboxylated prothrombin (PIVKA-II; a sensitive functional indicator of vitamin K status) before and for up to four days after a single dose of mixed micellar K-1 1 mg intravenously or 2 mg orally. Comparison of K, levels 24 hours after oral K-1 with those from 14 healthy newborns given the same dose. Results: At admission, 18 infants (41%) had elevated levels of serum PIVKA-II and eight (18%) had low K-1 concentrations, indicative of subclinical vitamin K deficiency. Median serum K-1 concentrations were similar in the oral and intravenous groups at baseline (0.92 v 1.15 ng/ml), rising to 139 ng/ml six hours after intravenous K-1 but to only 1.4 ng/ml after oral administration. In the latter group, the low median value (0.95 ng/ml) and wide range (< 0.15-111 ng/ml) of serum K-1 compared unfavourably with the much higher levels (median 77, range 11-263 ng/ml) observed in healthy infants given the same oral dose, and suggested impaired and erratic intestinal absorption in cholestatic infants. The severity of malabsorption was such that only 4/24 (17%) achieved an incremental rise in serum K-1 > 10 ng/ml. Conclusions: The intestinal absorption of mixed micellar K-1 is unreliable in infants with conjugated hyperbilirubinaemia. Given the strong association between cholestasis and late vitamin K deficiency bleeding, these data provide an explanation for the failure of some oral vitamin K-1 prophylaxis regimens in infants with latent cholestasis.
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