Discordance and bleeding in critically ill patients with COVID-19 receiving unfractionated heparin: A comparison between aPTT and anti-factor Xa activity level monitoring

Introduction: COVID-19 is associated with hypercoagulability and an increased risk of thrombotic complications. In critically ill COVID-19 patients with thrombosis receiving unfractionated heparin (UFH), heparin resistance is frequently observed when the activated Partial Thromboplastin Time (aPTT) is used for monitoring. It is unclear whether UFH monitoring with anti-factor Xa (anti-Xa) is beneficial. Methods: Retrospective cohort of critically ill COVID-19 patients treated with UFH in a single center tertiary Intensive Care Unit (ICU) before and after changing treatment protocol from a nurse-driven aPTT guided to an anti-Xa guided UFH dosing protocol. Measurements of aPTT and anti-Xa were simultaneously collected to evaluate discordance. Next, bleeding events while treated using the different treatments protocols was assessed, using the validated HEME scoring system. Results: We included 149 patients with a median age of 63 years (interquartile range: 59, 70). Among the 715 samples with simultaneous measurements of aPTT and anti-Xa, discordance was observed in 57 % of samples. This was based on a low aPTT and normal anti-Xa activity in 40 %, and a normal aPTT and high anti-Xa activity in 9 %. In the aPTT period 43 of 83 patients developed any bleeding (52 %) compared to 23 of 68 patients (34 %) in the anti-Xa-guided period. In the 83 patients in the aPTT guided group, there were 43 bleeding events in 19 patients, compared to 23 bleeding events in 16 patients in the group guided by anti-Xa activity. Conclusion: In critically ill patients with COVID-19 receiving UFH, measurement of aPTT and anti-Xa activity are frequently discordant. Anti-Xa monitoring could potentially help in reducing the risk of bleeding.