Monitoring of unfractionated heparin in critical ill ICU patients: a prospective study comparing aPTT and point-of-care viscoelastic testing with IN /HI ratio to anti-Xa

Introduction Anticoagulation is indicated for the prevention or therapy of thromboembolic events, but remains highly challenging considering the high risk of bleeding events in critically ill patients.Unfractionated heparin (UFH) is widely used as preferred anticoagulation for patients on intensive care units (ICU) due to its beneficial short half time and fast elimination. For monitoring of UFH, activated partial thromboplastin time (aPTT) is mainly used, but aPTT can be misleading in both directions [ 1 ]. While high factor VIII plasma values may decrease aPTT, a reduced factor XII under extracorporal circulation may prolong aPTT that no longer correlates to anticoagulation intensity [ 2 ]. Anticoagulation monitoring using specific UFH calibrated anti-Xa levels is an established alternative to overcome aPTT limitations but is rarely available 24/7 [ 3 ] [ 4 ]. Using point-of-care (POC) viscoelastic testing (VET) [ 5 ] with a specific ratio between clotting time (CT) in intrinsic test (IN-test) compared to heparinase test (HI-test) – which includes the inactivation of heparin in the probe - might help to determine the UFH effect in critically ill patients [ 6 ]. Method From 09/2020 to 07/2022, 467 samples from 120 adult ICU patients receiving UFH therapy were prospectively collected. Samples for aPTT, anti-Xa measurement and POC VET using ClotPro (Haemonetics, Boston, Massachusetts, USA) were simultaneously collected. Measurement for aPTT (C.K. Prest) and anti-Xa (Liquid AntiXa) were performed using STA R Max 3 device (Stago Deutschland GmbH, Düsseldorf). Correlation was analyzed using Kruskal-Wallis test in SPSS version 27 and R version 3.2.4. This study was approved by the local Ethics Committee at the Technische Universität Dresden, Germany (BO-EK- 374072021) and registered with the German Clinical Trials Register DRKS00028689. Results 467 samples under UFH treatment were included in this analysis, the majority of these patients were treated for COVID-19 associated acute distress syndrome. According to our institutional guidelines, anti-Xa target levels for UFH were set at 0.3-0.5 IE/ml for standard high-risk prophylaxis and 0.5-0.7 IE/ml for therapeutic anticoagulation therapy with values <0.3 and > 0.7 being defined as under- or over-treatment. Table 1 presents the median aPTT and CT IN/HI ratio values for patients within these anti-Xa categories. CT IN/HI ratio correlation to anti-Xa levels was considerably better than aPTT correlation ([ Tab. 1 ]). Notably, aPTT could not exactly discriminate between patients receiving UFH dosages correlating to high-risk prophylaxis or therapeutic anticoagulation. Tab. 1 median test values (1st; 3rd quartile) for each predefined ant-Xa target category Conclusion Whole blood POC VET using a specific heparinase-approach (IN/HI ratio) is superior to aPTT in detecting patients in or out of targeted anti-Xa levels. POC VET should be made available for ICUs as bedside test and might help to guide anticoagulation management in critical ill patients, being faster and potentially more widely available than lab-based anti-Xa testing ([ Fig. 1 ]). Fig. 1 Box plots comparing ClotPro IN/HI ratio and aPTT to dofferent clinical relevant predefined anti-Xa target categories in patients under anticoagulations with UFH. Publication History Article published online: 20 February 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany