Routine Coagulation Tests in Patients With Nonvalvular Atrial Fibrillation Under Dabigatran and Rivaroxaban Therapy: An Affordable and Reliable Strategy?

Abstract

Dabigatran and rivaroxaban, direct oral anticoagulants (DOACs), affect coagulation tests, and knowledge of their effects is important for therapeutic monitoring. Our aim was to examine the association between DOAC levels and routine coagulation tests in patients with nonvalvular atrial fibrillation. Samples from patients receiving dabigatran (150 mg) and patients receiving rivaroxaban (20 mg) were collected 2 hours after drug intake. Direct oral anticoagulant concentrations were determined using direct Hemoclot thrombin inhibitor (HTI) assay (HTI test) and a direct Xa inhibitor (Anti Xa-Riva). The routine coagulation measured included activated partial thromboplastin time (aPTT) and prothrombin time (PT). The median plasmatic dabigatran was 128.3 ng/mL (95% confidence interval [CI]: 93.7-222.6 ng/mL). The HTI exhibited a good correlation with aPTT ( R 2 = 0.74; P < .0001). The median plasmatic rivaroxaban was 223.9 ng/mL (95% CI: 212.3-238.9 ng/mL). Anti-Xa-Riva correlated with PT ( R 2 = 0.69, P < .0001) and aPTT (R 2 = 0.36, P < .001), but prolonged PT results were obtained, even below the rivaroxaban therapeutic range (20%). The routine coagulation tests were able to identify out of therapeutic range concentrations for dabigatran and rivaroxaban. We suggest the use of these screening tests to better understand and monitor the subtherapeutic concentrations of these DOACs.

Effects of dabigatran and rivaroxaban on stroke severity according to the results of routine coagulation tests

“…In our study, a longer aPTT was significantly associated with reduced stroke severity and a smaller infarction volume in patients receiving dabigatran. aPTT has been experimentally reported to correlate with plasma dabigatran concentration in a curvilinear manner [19][20][21][22]. We speculate that a longer aPTT in patients on dabigatran may result in a smaller embolus size, enhanced embolus resolution, and reduced thrombus propagation, which may lead to decreased stroke severity [23,24].…”

“…Previous experimental studies have revealed a linear correlation between PT and plasma rivaroxaban concentration [12,17,21]. However, aPTT may not be suitable for the evaluation of rivaroxaban activity because of its unresponsiveness and poor sensitivity to this DOAC [27].…”

Long-Term Anticoagulation in Secondary Ischemic Stroke Prevention: The Prospective Multicenter RESTAIC Registry

“…It would be interesting to have a reliable test to anticipate the therapeutic failure and then adapt a therapeutic strategy. In this regard a recent study suggests that the activity of anticoagulation measured by specific DOAC plasma levels on admission is associated with stroke severity (53), and some studies support the reliability of DOAC determination (54,55) especially in patients with acute ischemic stroke (56,57). However, the ideal test is not yet widely available, and more studies are needed to guide future treatment decisions (58,59).…”

A systematic review and meta‐analysis of dabigatran peak and trough concentration in adults

“…Fifteen studies with a total of 1226 patients were included in the meta-analysis. Eight studies [22][23][24][25]38,47,56,57 that reported only the central tendency or dispersion, but not both, were excluded from the meta-analysis because the mean and standard deviation could not be estimated. Five studies 20,26,43,52,58 with significantly skewed estimated mean and standard deviation were excluded as this estimation method is not recommended.…”