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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 Department of Gastroenterology, The Middlesex Hospital, University College London Hospitals NHS Trust, London, UK
² Vitamin K Research and Diagnostic Units, The Haemophilia Centre, St Thomas’ Hospital, London, UK
³ Institute of Hepatology, University College London, UK
⁴ Paediatric Liver Service, King’s College Hospital, London, UK

Correspondence to:
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

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.

Keywords: vitamin K; hyperbilirubinaemia; cholestasis; liver

Abbreviations: INR, international normalised (prothrombin) ratio; PIVKA, proteins induced by vitamin K absence or antagonism; VKDB, vitamin K deficiency bleeding

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