The Potential Impact of Dietary Vitamin K Status on Anticoagulation Control in Children Receiving Warfarin

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There have been significant advances in pediatric medical care and previously fatal conditions, such as congenital cardiac defects, malignancy, and prematurity, are now being successfully managed but at the expense of a rising incidence of thromboembolic complications [1]. The requirement for anticoagulation to treat thrombotic events, as well as for prophylaxis in at risk patients, is therefore increasing. Warfarin remains the anticoagulant of choice for long-term treatment in children. Maintenance of International Normalized Ratio (INR) within the target range is essential in order to prevent the hemorrhagic complications of overdosing and thrombotic events due to underdosing. Poor anticoagulant control is common in children who are anticoagulated with warfarin and other oral vitamin K antagonists, with around 50% of measured INR values being outside of the desired therapeutic range even when home monitoring with a point-of-care testing device is used [2, 3]. There are numerous reasons for poor oral anticoagulant control in children. These include complex underlying health problems, multiple intercurrent viral illnesses and polypharmacy [4]. The variability of age-related dose-response rates is an additional complexity to the appropriate dosing of warfarin in childhood [2]. Warfarin produces an anticoagulant effect by interfering with the cyclic conversion of vitamin K to its reduced form (vitamin K hydroquinone). The latter is an essential cofactor for the γ -carboxylation of the vitamin K–dependent coagulation factors (II, VII, IX, and X), which promotes their calcium binding and activation in the coagulation cascade [4]. The anticoagulant effect of warfarin can be antagonized by vitamin K. The administration of supraphysiological doses of vitamin K orally, intramuscularly, or intravenously is common practice in the reversal of over-anticoagulation with warfarin [5].