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Background: High levels of discordance between activated partial thromboplastin time (aPTT) and anti-factor Xa (anti-FXa) have been reported in patients with continuous-flow left ventricular assist devices (CF-LVADs). We sought to determine the biochemical basis for discordance by simultaneous measurement of coagulation factors with aPTT and anti-FXa., Methods: Consecutive CF-LVAD patients admitted for intravenous unfractionated heparin (IV-UFH) therapy were studied. IV-UFH was monitored based on an anti-FXa. International normalized ratio (INR), aPTT, lactate dehydrogenase, and coagulation factors II, V, VII, VIII, IX, X, XI, and XII were measured simultaneously with anti-FXa., Results: The discordance rate between anti-FXa and aPTT was 74.7% overall (568 of 760 samples from 62 patients). In samples in which coagulation factors were simultaneously measured, the discordance rate was 66% (49 of 74 samples from 52 patients). In patients with INR ≤ 1.0 the discordance level was 31.8% vs 82.7% with INR > 1.8. No difference was observed in the rate of discordance between samples with low vs normal vitamin K-dependent factors (65.9% vs 64.7%, p = 0.99). Low factor XII was found in 15%; of these, 90.9% exhibited anti-FXa/aPTT discordance. Low factor V was found in 8.2%, and all were discordant. Factor VIII was elevated in 97% of samples, and 65.7% were discordant., Conclusions: In addition to the effects of warfarin administration on aPTT, the influence of other factors, such as low factor XII or V, may contribute to the discordance between aPTT values and anti-FXa. Coagulation factor levels may assist in individualization of anti-coagulation targets while patients implanted with CF-LVADs are on IV-UFH., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)