Viscoelastic point-of-care testing for monitoring unfractionated heparin in critically ill patients: a prospective observational study comparing ClotPro® IN/HI-Test, aPTT and Anti-Xa activity.

BACKGROUND

Monitoring of unfractionated heparin (UFH) in critically ill patients is challenging due to disease-related alterations of the coagulation system, directly affecting conventional laboratory tests, including activated partial thromboplastin time (aPTT). Measurement of anti-factor Xa activity (Anti-Xa) as an alternative to aPTT often lacks 24/7 availability. Whole blood viscoelastic testing (VET) may provide a feasible point-of-care alternative to guide UFH dosing in this setting. Additionally, VET is readily available in the environment found in our clinic, The aim of this study was to evaluate the diagnostic performance of viscoelastic testing compared with activated partial thromboplastin time for monitoring unfractionated heparin in critically ill patients and to define clinically applicable viscoelastic thresholds using anti-factor Xa activity as the reference standard.

METHODS

In this prospective observational study for UFH monitoring Anti-Xa, aPTT, and the VET clotting time IN/HI ratio (ClotPro®; Haemonetics, Boston, MA, USA) were determined in simultaneously taken blood samples. Anti-Xa results were used as the reference standard to categorize ongoing UFH anticoagulation intensity into four categories (prophylactic, sub-therapeutic, therapeutic, and overdosed). Diagnostic performance of aPTT and CT IN/HI ratio were evaluated against Anti-Xa using ROC analysis and Cohen’s Kappa. Test performance was evaluated using ROC analysis, multiclass classification, and weighted Cohen’s kappa.

RESULTS

Between September 2020 and July 2022, 466 datasets from 75 ICU patients receiving intravenous UFH were analyzed. Compared to aPTT, AUC values for CT IN/HI were higher for detecting prophylactic (0.817 vs. 0.726), therapeutic (0.690 vs. 0.494) and overdosed (0.845 vs. 0.708) UFH levels. Thresholds of > 1.4, > 1.9, and > 2.3 for the CT IN/HI ratio corresponded to sub-therapeutic, therapeutic, and overdosed ranges, respectively. The CT IN/HI ratio showed moderate agreement with Anti-Xa classification (κ = 0.450), while aPTT agreement was insufficient (κ = 0.220).

CONCLUSIONS

The CT IN/HI ratio offers a reliable point-of-care alternative to standard UFH monitoring, in the case it is readily available. It provides better alignment with Anti-Xa activity than aPTT and may improve anticoagulation management in critically ill patients, especially when Anti-Xa testing is delayed or unavailable. TRIAL REGISTRATION: DRKS-ID DRKS00028689 ( https://drks.de/search/de ), PI: Lars Heubner, retrospectively registered 30.03.2022.