Dataset Information

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

ABSTRACT:

Background

Direct oral anticoagulants (DOAC) including edoxaban are increasingly used for stroke prevention in atrial fibrillation. Despite treatment, annual stroke rate in these patients remains 1-2%. Rapid assessment of coagulation would be useful to guide thrombolysis or reversal therapy in this growing population of DOAC/edoxaban-treated stroke patients. Employing the Hemochron™ Signature Elite point-of-care test system (HC-POCT), clinically relevant plasma concentrations of dabigatran and rivaroxaban can be excluded in a blood sample. However, no data exists on the effect of edoxaban on HC-POCT results. We evaluated whether edoxaban plasma concentrations above the current treatment thresholds for thrombolysis or anticoagulation reversal (i.e., 30 and 50 ng/mL) can be ruled out with the HC-POCT.

Methods

We prospectively studied patients receiving a first dose of edoxaban. Six blood samples were collected from each patient: before, 0.5, 1, 2, 8, and 24 h after drug intake. HC-POCT-based INR (HC-INR), activated clotting time (HC-ACT+ and HC-ACT-LR), activated partial thromboplastin time (HC-aPTT), and mass spectrometry for edoxaban plasma concentrations were performed at each time-point. We calculated correlations, receiver operating characteristics (ROC) and test-specific cut-offs for ruling out edoxaban concentrations > 30 and > 50 ng/mL in a blood sample.

Results

One hundred twenty blood samples from 20 edoxaban-treated patients were analyzed. Edoxaban plasma concentrations ranged from 0 to 512 ng/mL. HC-INR/HC-ACT+/HC-ACT-LR/HC-aPTT ranged from 0.7-8.3/78-310 s/65-215 s/19-93 s, and Pearson's correlation coefficients showed moderate to very strong correlations with edoxaban concentrations (r = 0.95/0.79/0.70/0.60). With areas under the ROC curve of 0.997 (95% confidence interval: 0.991-0.971) and 0.989 (0.975-1.000), HC-INR most reliably ruled out edoxaban concentrations > 30 and > 50 ng/mL, respectively, and HC-INR results ≤1.5 and ≤ 2.1 provided specificity/sensitivity of 98.6% (91.2-99.9)/98.0% (88.0-99.9) and 96.8% (88.0-99.4)/96.5% (86.8-99.4).

Conclusions

Our study represents the first systematic evaluation of the HC-POCT in edoxaban-treated patients. Applying sufficiently low assay-specific cut-offs, the HC-POCT may not only be used to reliably rule out dabigatran and rivaroxaban, but also very low edoxaban concentrations in a blood sample. Because the assay-specific cut-offs were retrospectively defined, further investigation is warranted.

Trial registration

ClinicalTrials.gov, registration number: NCT02825394 , registered on: 07/07/2016, URL.

SUBMITTER: Hartig F

PROVIDER: S-EPMC7919064 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background During treatment with direct oral anticoagulants ( DOAC ), coagulation assessment is required before thrombolysis, surgery, and if anticoagulation reversal is evaluated. Limited data support the accuracy of DOAC -specific coagulation assays around the current safe-for-treatment threshold of 30 ng/ mL . Methods and Results In 481 samples obtained from 96 patients enrolled at a single center, DOAC concentrations were measured using Hemoclot direct thrombin inhibitor assay, Biophen direct thrombin inhibitor assay or ecarin clotting time for dabigatran, chromogenic anti-Xa assay ( AXA ) for factor Xa inhibitors (rivaroxaban, apixaban) and ultraperformance liquid chromatography-tandem mass spectrometry as reference. All dabigatran-specific assays had high sensitivity to concentrations >30 ng/ mL , but specificity was lower for Hemoclot direct thrombin inhibitor assay (78.2%) than for Biophen direct thrombin inhibitor assay (98.9%) and ecarin clotting time (94.6%). AXA provided high sensitivity and specificity for rivaroxaban, but low sensitivity for apixaban (73.8%; concentrations up to 82 ng/ mL were misclassified as <30 ng/ mL ). If no DOAC -specific calibration for AXA is available, results 2-fold above the upper limit of normal indicate relevant rivaroxaban concentrations. For apixaban, all elevated results should raise suspicion of relevant anticoagulation. Conclusions DOAC -specific tests differ considerably in diagnostic performance for concentrations close to the currently accepted safe-for-treatment threshold. Compared with Biophen direct thrombin inhibitor assay and ecarin clotting time, limited specificity of Hemoclot direct thrombin inhibitor assay poses a high risk of unnecessary anticoagulation reversal or treatment delays in patients on dabigatran. While AXA accurately detected rivaroxaban, the impact of low apixaban levels on the assay was weak. Hence, AXA results need to be interpreted with extreme caution when used to assess hemostatic function in patients on apixaban. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 02371044, NCT 02371070.

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