Monitoring of Unfractionated Heparin Therapy in the Intensive Care Unit Using a Point-of-Care aPTT: A Comparative, Longitudinal Observational Study with Laboratory-Based aPTT and Anti-Xa Activity Measurement

Abstract

Continuous intravenous unfractionated heparin (UFH) is administered routinely in the intensive care unit (ICU) for the anticoagulation of patients, and monitoring is performed by the activated partial thromboplastin time (APTT) or anti-Xa activity. However, these strategies are associated with potentially large time intervals before dose adjustments, which could be detrimental to the patient. The aim of the study was to compare a point-of-care (POCT) version of the APTT to (i) laboratory-based APTT and (ii) measurements of anti-Xa activity in terms of correlation, agreement and turnaround time (TAT). Thirty-five ICU patients requiring UFH therapy were prospectively included and followed longitudinally for a maximum duration of 15 days. UFH was administered according to a local adaptation of Raschke and Amanzadeh’s aPTT nomograms. Simultaneous measurements of POCT-APTT (CoaguCheck® aPTT Test, Roche Diagnostics) on a drop of fresh whole blood, laboratory-based APTT (C.K. Prest®, Stago) and anti-Xa activity (STA®Liquid anti-Xa, Stago) were systematically performed two to six times a day. Antithrombin, C-reactive protein, fibrinogen, factor VIII and lupus anticoagulant were measured. The time tracking of sampling and analysis was recorded. The overall correlation between POCT-APTT and laboratory APTT (n = 795 pairs) was strongly positive (rs = 0.77, p < 0.0001), and between POCT-APTT and anti-Xa activity (n = 729 pairs) was weakly positive (rs = 0.46, p < 0.0001). Inter-method agreement (Cohen’s kappa (k)) between POCT and laboratory APTT was 0.27, and between POCT and anti-Xa activity was 0.30. The median TATs from sample collection to the lab delivery of results for lab-APTT and anti-Xa were 50.9 min (interquartile range (IQR), 38.4–69.1) and 66.3 min (IQR, 49.0–91.8), respectively, while the POCT delivered results in less than 5 min (p < 0.0001). Although the use of the POCT-APTT device significantly reduced the time to results, the results obtained were poorly consistent with those obtained by lab-APTT or anti-Xa activity, and therefore it should not be used with the nomograms developed for lab-APTT.

An Agreement Study Between Point-of-Care and Laboratory Activated Partial Thromboplastin Time for Anticoagulation Monitoring During Extracorporeal Membrane Oxygenation

“…In our study, we found that fibrinogen affected the bias between POC-aPTT and LAB-aPTT. A recent study also found that increased fibrinogen, FVIII, FXI, and FXII levels in ICU patients attenuated the association between POC-aPTT and LAB-aPTT (19). Toulon found the agreement between POC-aPTT (CoaguChek TM Pro DM) and LAB-aPTT was unacceptable in patients undergoing bleeding surgery (20), and the bias of POC and LAB -aPTT increased with the increasing severity of coagulopathy.…”

“…The turnaround time of POC-aPTT is much shorter than LAB-aPTT. Lardinois reported that the turnaround time of LAB-aPTT was 92.0 min (IQR, 69.3–121.2), much longer than that of POC-aPTT ( P < 0.0001) ( 19 ). A shorter turnaround time could help reduce thrombotic and hemorrhagic complications by avoiding insufficient or excessive anticoagulation, especially in the early stage of the ECMO run.…”

Whole-blood Point-of-Care Activated Partial Thromboplastin Time Ratio (APR) is not Accurate Enough to Monitor Heparin Therapy in Patients with Severe Respiratory Failure Secondary to SARS-Cov-2 Infection Supported with Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO)

“…While the present study did not look at the effect of the POC results on heparin infusion management, the correction of our aPTT results for the bias did not result in improved agreement between the aPTT measurement methods. In a very recent study Lardinois et al 17 compared the CoaguCheck ® with a laboratory measured aPTT and anti-Xa activity in a diverse group of 35 intensive care patients requiring continuous high- or low-range heparin infusions. These authors found the inter-method agreement between POC aPTT and laboratory aPTT to be 0.27 and between POC aPTT and anti-Xa to be 0.3.…”