Intestinal absorption of mixed micellar phylloquinone (vitamin K1) is unreliable in infants with conjugated hyperbilirubinaemia: implications for oral prophylaxis of vitamin K deficiency bleeding
- 1Department of Gastroenterology, The Middlesex Hospital, University College London Hospitals NHS Trust, London, UK
- 2Vitamin K Research and Diagnostic Units, The Haemophilia Centre, St Thomas’ Hospital, London, UK
- 3Institute of Hepatology, University College London, UK
- 4Paediatric Liver Service, King’s College Hospital, London, UK
- Correspondence to:
Dr Pereira, Department of Gastroenterology, The Middlesex Hospital, University College London Hospitals NHS Trust, Mortimer Street, London W1N 8AA, UK;
steve.pereira{at}uclh.org
- Accepted 28 April 2002
Abstract
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 K1 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 K1 1 mg intravenously or 2 mg orally. Comparison of K1 levels 24 hours after oral K1 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 K1 concentrations, indicative of subclinical vitamin K deficiency. Median serum K1 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 K1 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 K1 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 K1 > 10 ng/ml.
Conclusions: The intestinal absorption of mixed micellar K1 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 K1 prophylaxis regimens in infants with latent cholestasis.
- INR, international normalised (prothrombin) ratio
- PIVKA, proteins induced by vitamin K absence or antagonism
- VKDB, vitamin K deficiency bleeding
