Oral Anticoagulant Overdose: the Old and the New
1Clinical Toxicology Research Group, University of Newcastle, Australia
Anticoagulant overdoses are uncommon, but often difficult to manage due to potential ongoing requirements for anticoagulation and lack of antidotes for the newer oral anticoagulants (NOAC). Over-anticoagulation is a more common problem with all these agents but will not be considered here. Warfarin overdose is a good example of delayed drug effects and a mismatch between the pharmacokinetics of warfarin and the antidote vitamin K. Treatment is determined by whether the patient requires critical ongoing anticoagulation (e.g. heart valve) – in these cases anticoagulation with heparin is advisable when reversing warfarin. In patients not regularly on warfarin or can be reversed safely in the short term (e.g. atrial fibrillation), larger regular doses of vitamin K can be used. In all cases regular prothrombin times (international normalised ratio [INR]) should be done and if the INR increases on a subsequent occasion, further vitamin K is required. This is because vitamin K has a short half-life of 2-3h while warfarin has a half-life of 24-48h. The NOACs are becoming more common in overdose and the main issue is measuring the anticoagulant effect. Assays exist for each of the NOACs, but standard coagulation studies (activated partial thromboplastin time [aPTT] and INR) are likely sufficient for NOAC overdoses. These agents may not affect the INR and aPTT for therapeutic doses, so if these clotting studies are abnormal in overdose, they indicate coagulopathy. Treatment of NOAC overdose is also unclear, and there is little evidence to support the use of specific antidotes or factor replacement. Often supportive care, careful observation and serial coagulation studies will be sufficient.