Vitamin K deficiency bleeding in cholestatic infants with Alpha-1-Antitrypsin deficiency

Peter M van Hasselt ^1*, Karin Kok ², Adriane D M Vorselaars ¹, Lotte van Vlerken ¹, Ed Nieuwenhuys ³, Tom J de Koning ¹, Richard A de Vries ⁴ and Roderick H J Houwen MD PhD¹

¹ Department of Pediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Netherlands
² Division of Gastroenterology and Hepatology, Radboud University Medical Center Nijmegen, Netherlands
³ Department of Immunochemistry, Sanquin Diagnostics, Amsterdam, Netherlands
⁴ Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, Netherlands

^* To whom correspondence should be addressed. E-mail: p.vanhasselt{at}umcutrecht.nl.

Accepted 19 April 2009

Abstract

Objective: Exclusively breast-fed infants with unrecognized cholestatic jaundice are at high risk of a vitamin K deficiency (VKD) bleeding. It is presently unknown whether (the size of) this risk depends on the degree of cholestasis. Since alpha-1-antitrypsin deficiency (A1ATD) induces a variable degree of cholestasis, we assessed the risk of VKD bleeding in infants with cholestatic jaundice due to A1ATD.

Patients and methods: Infants with a ZZ or SZ phenotype born in the Netherlands between January 1991 and December 2006 were identified from the databases of the 5 Dutch diagnostic centres for alpha-1-antitrypsin phenotyping and/or genotyping. We determined the risk of VKD bleeding upon diagnosis of A1ATD in breastfed and formula-fed infants and searched for correlations between serum levels of conjugated bilirubin and the risk of bleeding.

Results: A total of 40 infants with A1ATD were studied. VKD bleeding was noted in 15/20 (75%) of breast-fed infants, compared with 0/20 of formula-fed infants with A1ATD. The relative risk for VKD bleeding in breast-fed versus formula-fed infants was at least 15.8 (95% confidence interval 2.3 to 108). Conjugated bilirubin levels at diagnosis did not correlate with the risk of VKD bleeding.

Conclusions: The risk of VKD bleeding in breast-fed infants with A1ATD was high and did not correlate with serum level of conjugated bilirubin at diagnosis. A similar absolute risk was previously reported in breast-fed infants with biliary atresia under the same prophylactic regimen. This confirms that - without adequate prophylaxis - the risk of VKD bleeding is uniformly high in exclusively breast-fed infants with cholestatic jaundice, irrespective of underlying etiology.