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.

Keywords: APTT; POCT; anti-Xa; heparin; monitoring; unfractionated heparin.

Figure 1

Flow diagram of identification, eligibility and inclusion processes. The basal POCT is the first POCT obtained before starting UFH administration. COVID, coronavirus disease 2019; POCT, point of care test; UFH, unfractionated heparin.

Figure 2

Overall correlation of POCT-APTT vs. laboratory APTT (left panel, n = 795) and POCT-APTT vs. anti-Xa (right panel, n = 729) from the 35 patients included in the study.

Figure 3

Temporal changes in POCT-APTT (brown), lab-APTT (blue) and anti-Xa (orange) levels during ICU stays for the 35 patients. Major or minor bleedings are symbolized by red triangles or dots above the graphs, respectively. No thrombotic events were recorded. APTT, activated partial thromboplastin time; ICU, intensive care unit; POCT, point-of-care testing.

Figure 4

Correlations of the POCT-APTT ratios vs. laboratory APTT ratios (left panels) and POCT-APTT ratios vs. chromogenic anti-Xa activity measurement (right panels), according to overall (top panels), high (center panels) or low (bottom panels) therapeutic target ranges from the 29 patients with basal POCT and basal lab-APTT measurements. The grey zone corresponds to the desired therapeutic range and tick lines represent the lower and the upper limits of this range for the corresponding assay. Pairs in agreement, unsatisfactory and contradictory categories are symbolized by green, orange and red dots, respectively. APTT, activated partial thromboplastin time; POCT, point-of-care testing; rs, Spearman correlation coefficient.

Figure 5

Relationships and inter-method agreements for POCT-APTT ratios vs. laboratory APTT ratios (left histograms) and POCT-APTT ratios vs. anti-Xa (right histograms), according to overall, low or high therapeutic ranges. Cohen’s Kappa coefficients are shown below each corresponding histogram.

Figure 6

Turnaround times from sample collection to delivery results for POCT-APTT (brown), lab-APTT (blue) and anti-Xa (orange).