Comparison of the effects of different treatment protocols on mortality in patients presenting with an INR? 10 due to warfarin-associated over-anticoagulation

Aim: One of the most anticipated adverse effects of warfarin is over-anticoagulation. There is little to no evidence on the treatment that should be administered in patients with an international normalized ratio (INR) >= 10. The primary outcome of this study is to analyze the effects of various treatments on 30-day mortality in patients with INR >= 10 and without major bleeding on 30-day all-cause mortality. The secondary outcome is to propose a model that predicts 30-day all-cause mortality in the same patient group.Methods: Patients older than 18 years of age using warfarin and who had an INR >= 10 were included in this retrospective cohort study. Patients with major bleeding on admission were excluded. Patients treated with only cessation of warfarin were named as "Group-1 ", patients who were treated with vitamin-K in addition to cessation of warfarin were named as "Group-2 ", and patients who were treated with cessation of warfarin and vitamin-K and fresh frozen plasma or prothrombin complex concentrate were named as "Group-3 ".Results: 190 patients were included in the analysis. Seven (38.9%) patients in the first group, 3 (8.6%) in the second group, and 21 (15.3%) in the third group died within 30-days(p = 0.015) . In the post-hoc analysis, the difference between Group-1 and Group-2 was found to be significant(p= 0.036, OR:0.147, 95%CI = 0.032 to 0.671).The performance of the model in predicting 30-day all-cause mortality was high (AUC = 0.818 (95%CI = 0.716 to 0.920) and found to be compatible with the validation dataset 0.806 (95%CI = 0.631 to 0.981). Administration of vitamin K in addition to the cessation of warfarin was found to be a strong contributor to the model and an independent predictor of survival within 30 days(p = 0.006 ).Conclusions: Until randomized controlled studies are conducted, it may be reasonable to administer vitamin-K in addition to cessation of warfarin in non-bleeding patients with INR >= 10.