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Intestinal absorption of mixed micellar phylloquinone (vitamin K1) is unreliable in infants with conjugated hyperbilirubinaemia: implications for oral prophylaxis of vitamin K deficiency bleeding
  1. S P Pereira1,
  2. M J Shearer2,
  3. R Williams3,
  4. G Mieli-Vergani4
  1. 1Department of Gastroenterology, The Middlesex Hospital, University College London Hospitals NHS Trust, London, UK
  2. 2Vitamin K Research and Diagnostic Units, The Haemophilia Centre, St Thomas’ Hospital, London, UK
  3. 3Institute of Hepatology, University College London, UK
  4. 4Paediatric Liver Service, King’s College Hospital, London, UK
  1. 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

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.

  • vitamin K
  • hyperbilirubinaemia
  • cholestasis
  • liver
  • INR, international normalised (prothrombin) ratio
  • PIVKA, proteins induced by vitamin K absence or antagonism
  • VKDB, vitamin K deficiency bleeding

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