Medline ® Abstract for Reference 66

BACKGROUND: Increasing numbers of children are being administered warfarin therapy as thromboprophylaxis. Warfarin has a narrow therapeutic window with a target international normalised ratio (INR) of 2-3.5, called the therapeutic range. The length of time a patient's INR remains within the therapeutic range is calculated as 'time in the therapeutic range'. Risk for haemorrhage in children receiving warfarin is 0.5%/patient-year and minor bleeding 2.3%/patient-year, which increases exponentially for INRs>5.0. Practice among non-bleeding adults with INRs≥5 and≤9 is to withhold warfarin and allow the INR to return to the therapeutic range. Faster warfarin clearance is correlated with younger age.

METHODS AND RESULTS: The study objective was to determine the safety and effectiveness of a conservative approach for management of INRs>5 in children receiving warfarin. Children receiving warfarin with INRs≥5 had warfarin withheld followed by a next day INR without vitamin K administration. Eighty-nine children (1-16 years) participated in the study with 2353 INRs performed. Twenty-six children had INRs≥5, 5% of the total performed, with a mean INR of 5.9. The next day repeat mean INR after withholding one dose of warfarin was 3.3 (range 1.2-6.8)with 89% of INRs falling below 5. There were no overt bleeds or symptomatic thrombotic events in the month following the INR>5. Time in the therapeutic range for children with INRs≥5 was 68%.

CONCLUSIONS: Withholding warfarin alone for management of non-bleeding INRs≥5 and≤8 appears to be safe and effective.