Determining Cause for Activated Partial Thromboplastin Time and Anti-Factor Xa Discordance in Mechanical Circulatory Support Patients on Heparin; Can Thromboelastogram Help?

Abstract

<h3>Purpose</h3> Both activated partial thromboplastin time (aPTT) and anti-Xa levels are used to monitor unfractionated heparin (UFH) in mechanical circulatory support (MCS) patients. Studies have demonstrated high level of discordance between these assays, particularly in critically ill patients. Thromboelastogram (TEG) is an assay that provides a graphical representation of hemostasis, and it may aid in guiding decision-making in discordant patients. The objective of this pilot study is to identify the causes of aPTT and anti-Xa discordance and to evaluate the potential benefit of TEG in guiding MCS patient's anticoagulation management. <h3>Methods</h3> A total of 18 patients receiving UFH with consecutive discordant aPTT/anti-Xa assays between April to August 2021 underwent 27 comprehensive evaluations. For each patient concurrent aPTT and anti-Xa assay data were collected for 2 days and 1 day prior to the date of TEG (69 evaluations). Discordance was considered as a 20 second difference between measured aPTT and calculated aPTT corresponding with the anti-Xa value. Results of TEG, antithrombin (AT)3, lupus anticoagulant (LA), free plasma hemoglobin and anticoagulation therapy outcomes one-week post-TEG were also collected. Results were interpreted by a hematopathologist with expertise in hemostasis who made recommendations regarding therapy and the best assay to monitor UFH. <h3>Results</h3> A dose response curve calculated from the paired aPTT/anti-Xa data showed a high degree of variability in aPTT for an anti-Xa assay level of 0.1-0.4 IU/mL (R² = 0.07). In 29/69 (42%) of the paired values, discordance was caused by the presence of LA affecting aPTT. When evaluated in conjunction with TEG, 12/24 (50%) values were positive for LA, 5/25 (20%) values had AT3 <60%, 11/27 (37%) patients had underlying factor deficiency determined by TEG, and 0/19 (0%) values had free Hgb >100 mg/dL. There were 6/27 bleeding events (22 %): epistaxis (1), melena (3), vaginal spotting (1), and hematoma (1). <h3>Conclusion</h3> Lupus anticoagulant, factor deficiency, and warfarin administration are the main causes for aPTT and anti-Xa discordance in MCS patients on heparin. TEG, in combination with LA and AT3 can help in identifying discordance cause, assess overall hemostasis, and the most appropriate parameter to monitor heparin.