Point-of-care testing for emergency assessment of coagulation in patients treated with direct oral anticoagulants

Matthias Ebner, Ingvild Birschmann, Andreas Peter, Charlotte Spencer, Florian Härtig, Joachim Kuhn, Gunnar Blumenstock, Christine S Zuern, Ulf Ziemann, Sven Poli, Matthias Ebner, Ingvild Birschmann, Andreas Peter, Charlotte Spencer, Florian Härtig, Joachim Kuhn, Gunnar Blumenstock, Christine S Zuern, Ulf Ziemann, Sven Poli

Abstract

Background: Point-of-care testing (POCT) of coagulation has been proven to be of great value in accelerating emergency treatment. Specific POCT for direct oral anticoagulants (DOAC) is not available, but the effects of DOAC on established POCT have been described. We aimed to determine the diagnostic accuracy of Hemochron® Signature coagulation POCT to qualitatively rule out relevant concentrations of apixaban, rivaroxaban, and dabigatran in real-life patients.

Methods: We enrolled 68 patients receiving apixaban, rivaroxaban, or dabigatran and obtained blood samples at six pre-specified time points. Coagulation testing was performed using prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and activated clotting time (ACT+ and ACT-low range) POCT cards. For comparison, laboratory-based assays of diluted thrombin time (Hemoclot) and anti-Xa activity were conducted. DOAC concentrations were determined by liquid chromatography-tandem mass spectrometry.

Results: Four hundred and three samples were collected. POCT results of PT/INR and ACT+ correlated with both rivaroxaban and dabigatran concentrations. Insufficient correlation was found for apixaban. Rivaroxaban concentrations at <30 and <100 ng/mL were detected with >95% specificity at PT/INR POCT ≤1.0 and ≤1.1 and ACT+ POCT ≤120 and ≤130 s. Dabigatran concentrations at <30 and <50 ng/mL were detected with >95% specificity at PT/INR POCT ≤1.1 and ≤1.2 and ACT+ POCT ≤100 s.

Conclusions: Hemochron® Signature POCT can be a fast and reliable alternative for guiding emergency treatment during rivaroxaban and dabigatran therapy. It allows the rapid identification of a relevant fraction of patients that can be treated immediately without the need to await the results of much slower laboratory-based coagulation tests.

Trial registration: Unique identifier, NCT02371070 . Retrospectively registered on 18 February 2015.

Keywords: Anticoagulation reversal; DOAC; Direct oral anticoagulants; Emergency surgery; NOAC; Non-vitamin K antagonist oral anticoagulants; POCT; Point-of-care testing; Stroke; Thrombolysis.

Figures

Fig. 1
Fig. 1
Hemochron® Signature POCT results (lines 1 to 4) plotted against concentrations of a apixaban, b rivaroxaban, and c dabigatran. Line 1: prothrombin time/international normalized ratio (PT/INR) POCT; line 2: activated partial thromboplastin time (aPTT) POCT; line 3: activated clotting time-low range (ACT-LR) POCT; line 4: ACT+ POCT. n = 118 samples for rivaroxaban, n = 117 samples for apixaban, and n = 168 samples for dabigatran
Fig. 2
Fig. 2
a Distribution of rivaroxaban concentrations found at different Hemochron® Signature POCT results of prothrombin time/international normalized ratio (PT/INR) and activated clotting time plus (ACT+) test cards and at different anti-Xa activities (n = 118 samples). b Distribution of dabigatran concentrations found at different Hemochron® Signature POCT results of PT/INR and ACT+ test cards, and at different Hemoclot assay results (n = 168 samples)
Fig. 3
Fig. 3
Proposed algorithm for emergency coagulation assessment in rivaroxaban- and dabigatran-treated patients. DOAC direct oral anticoagulant, POCT point-of-care test
Fig. 4
Fig. 4
Scatter plot of rivaroxaban concentrations (green area: <30 ng/mL) and activated clotting time (ACT+) POCT illustrating the diagnostic accuracy of POCT results. Green diamonds represent samples below the safe-for-treatment threshold that are correctly identified as eligible for immediate treatment (true positive). Blue crosses represent samples that are not detected although containing concentrations below the safe-for-treatment threshold (false negative). These can potentially still receive delayed treatment if slower laboratory-based DOAC-specific tests are available. Green crosses represent samples above the POCT cut-off correctly identified as not eligible for treatment (true negative). Red diamonds represent the few samples incorrectly identified as eligible for treatment despite concentrations above the safe-for-treatment threshold (false positive)

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