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Letter to the Editor

Vitamin K May Be A-OK, in Kids and Cholestatic Patients

Giulia Jannone
Marie-Astrid van Dievoet
Louise Coppin
Etienne Sokal
Xavier Stephenne

To the Editor:

We would like to thank the authors of the article “Routine Use of Vitamin K in the Treatment of Cirrhosis-Related Coagulopathy: Is it A-O-K? Maybe Not, We Say,” published in the March 2019 issue, for discussing this very interesting subject. However, we wish to share some concerns about the very strong message sent by this article against vitamin K administration in cirrhotic patients. In our opinion, the evidence presented is insufficient to draw such conclusions.

First, the clinical cases lack some critical information in order for readers to understand if the elevated international normalized ratio (INR) at baseline was related to vitamin K deficiency, and if this potential deficit was secondary to impaired liver function and/or cholestasis. It would have been useful to dose PIVKA-II and vitamin K-dependent coagulation factor levels at baseline and after vitamin K administration, as well as factor V and direct bilirubin levels at baseline.

Although the cases presented involved adult patients, no distinction was made between adult and pediatric patients. However, articles on the pediatric population are cited. Mager et al.’s work, described in the paper, showed that there is a deficit of vitamin K in pediatric cholestatic liver diseases. Strople et al. also provided evidence that all of their cholestatic adult and pediatric patients with elevated INR showed an associated vitamin K deficit. This deficit was not corrected by oral vitamin K administration because intestinal absorption is compromised in cholestasis, but intravenous vitamin K administration was not investigated in this study. Both studies suggested a correlation between vitamin K deficit and disease severity. Takahashi et al.1 recently highlighted the prevalence of intracranial hemorrhage in young patients (aged 0–3 months) in biliary atresia as a result of vitamin K deficiency related to cholestasis. They emphasize the importance of intramuscular vitamin K injection to avoid this severe bleeding complication.1

Concerning the use of vitamin K in cirrhosis, the authors cite Shah et al., who still recommend the preventive use of the vitamin in liver disease despite its lack of impact on clinical outcome, because of the prevalence of vitamin K deficiency in this population. They also cite the work of Saja et al., which indicated an improved prothrombin time 72 hours after subcutaneous vitamin K administration, regardless of the fact that no vitamin K deficiency was indicated at baseline. On the other hand, Blanchard et al. did not show any decrease in prothrombin time after vitamin K administration, but the route of administration is not specified and the observation includes only seven patients with cirrhosis (and no specifications about cholestasis). Finally, they cite Feldshon et al., who did not show any improvement in coagulation parameters after vitamin K administration; no information is provided about the number of patients and disease, or about the administration regimen.

The authors also discuss the fact that elevated INR does not protect against venous thromboembolic risk and that adult patients with cirrhosis are at greater risk of venous thromboembolism than the general population, as confirmed in a recent meta-analysis by Ambrosino et al.2 However, thrombotic complications are not common in pediatric patients, and no study is cited about the potential prothrombotic effect of vitamin K.

The authors conclude that the routine use of vitamin K should be avoided in liver cirrhosis in the absence of active bleeding as it has no demonstrated benefits on clinical outcome and could potentially have prothrombotic effects.

In light of the information given, it seems clear that the prevalence of vitamin K deficiency is high in chronic liver disease, and even higher in cholestatic liver disease. The administration of vitamin K has no demonstrated beneficial impact on clinical outcome, but does seem to improve coagulation parameters in some studies. In addition, the potential prothrombotic effect of vitamin K administration has not been demonstrated or even investigated to date.

We believe that avoiding the routine use of vitamin K could be harmful for certain patients, especially pediatric and cholestatic ones. We agree with the authors that further studies are needed to assess the safety, efficacy, and impact on clinical outcome. We thank you for your attention and are at your disposal for any further discussion on this topic.

Author bio: 
Pediatric Gastroenterology and Hepatology Division Cliniques Universitaires Saint-Luc – UCL Brussels, Belgium

References

  1. Takahashi Y, Matsuura T, Yoshimaru K, et al. Comparison of biliary atresia with and without intracranial hemorrhage. J Pediatr Surg 2018;53;(11):2245–2249.10.1016/j.jpedsurg.2018.04.031
  2. Ambrosino P, Tarantino L, Di Minno G, et al. The risk of venous thromboembolism in patients with cirrhosis: a systematic review and meta-analysis [published online October 20, 2016]. Thromb Haemost 2017;117;(1):139–148.10.1160/TH16-06-0450