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.
Highlights
Despite the advent of low molecular weight heparins (LMWHs), continuous intravenous (IV) unfractionated heparin (UFH) anticoagulation remains useful in the intensive care unit (ICU) in several indications, such as circulatory assist devices, severe renal failure and high bleeding risk.Patients treated with UFH are commonly monitored by the activated partial thromboplastin time (APTT) [1]
We investigated the comparison of a point-of-care version of the APTT to the labWe investigated the comparison of a point-of-care version of the APTT to the labAPTT assay and anti-Xa activity for monitoring UFH therapy in the ICU
We studied the effect of known confounding factors on APTT measurements and found that C-reactive protein (CRP), fibrinogen, factor XII
Summary
Despite the advent of low molecular weight heparins (LMWHs), continuous intravenous (IV) unfractionated heparin (UFH) anticoagulation remains useful in the intensive care unit (ICU) in several indications, such as circulatory assist devices, severe renal failure and high bleeding risk.Patients treated with UFH are commonly monitored by the activated partial thromboplastin time (APTT) [1]. Basu et al in 1972 [5], the lack of international standardization [4], the presence of a high technical bias [6,7] and many confounding factors affecting this test (e.g., low fibrinogen or coagulation factor levels, high factor VIII levels, presence of a lupus anticoagulant (LA), preactivation of samples during difficult collection). In this context, monitoring and dose titration of IV UFH by chromogenic anti-Xa activity measurement has been suggested as the preferred method, given its more specific assessment of heparin levels and its independence from inflammatory factors. The commonly accepted therapeutic range of 0.3–0.7 IU/mL of this assay is not yet clinically validated and shows wide variations between laboratories [8]
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