Detecting clinically relevant rivaroxaban or dabigatran levels by routine coagulation tests or thromboelastography in a cohort of patients with atrial fibrillation

Abstract

BackgroundTraditional coagulation tests are included in emergency guidelines for management of patients on direct oral anticoagulants (DOACs) who experience acute bleeding or require surgery. We determined the ability of traditional coagulation tests and fast whole blood thromboelastography (ROTEM®) to screen for anticoagulation activity of dabigatran and rivaroxaban as low as 30 ng/mL.MethodsOne hundred eighty-four citrated blood samples (75 dabigatran, 109 rivaroxaban) were collected from patients with non-valvular atrial fibrillation (NVAF), to perform screening tests from different manufacturers, (diluted, D) PT, aPTT, TT and ROTEM®. The activity of DOACs was quantitatively determined by clot detection assays: Hemoclot DTT and DiXaI test (Biophen), on CS2100 (Siemens). The clotting time (CT) of INTEM and EXTEM ROTEM® (Werfen) were used as test parameters.ResultsDabigatran, ≥ 30 ng/mL, was accurately detected by five coagulation tests: APTT Actin FSL (93%), PT Neoplastin (93%), APTT Cephascreen, Thromboclotin, and Thrombin (all 100%), but not by PT Innovin (49%). CT-EXTEM (91%) was sufficiently sensitive, but not CT-INTEM (52%). APTT Cephascreen and Thrombin showed good linearity (R2 = 0.71,R2 = 0.72). For the other tests linearity was moderate to poor. Rivaroxaban was accurately detected by PT Neoplastin (98%) and less so by APTT Cephascreen (85%). In addition, rivaroxaban was also accurately detected by CT-INTEM (96%). PT Neoplastin showed good linearity (R2 = 0.81), all other tests had moderate to poor linearity.ConclusionIn patients with NVAF, the ability of routine coagulation tests to detect the presence of significant levels of DOACs is test and reagent dependent. CT-INTEM and CT-EXTEM may be fast whole blood alternatives.Trial registrationThe Institutional Review Board of the MUMC approved this study (December 2011, project number 114069).

Monitoring DOACs with a Novel Dielectric Microsensor: A Clinical Study

“…In contrast to the results shown here, previously published studies reported the sensitivity of PT for rivaroxaban to range from 59 to 98% among thromboplastin reagents. 1,33,34,[38][39][40][41] For apixaban, across in vitro and ex vivo samples for a variety of reagents, the correlation between PT and on-treatment apixaban levels was modest, with R 2 values of 0.36 to 0.41. 33,34 As with PT, commercial aPTT reagents differ in their sensitivity to dabigatran.…”

Direct oral anticoagulants: When to consider laboratory testing?

“…Moreover, there is still a need for faster, whole blood assays to exclude the presence of clinically relevant DOAC levels. Faster whole blood tests such as ROTEM EXTEM clotting time (thromboelastography) had similar or even better sensitivity for ruling out clinically relevant levels of rivaroxaban compared to the frequently used aPTT (Cephascreen/Actin FSL) or PT (Neoplastin/Innovin) reagents . However, the cost‐effectiveness of the use of such laboratory assays merits attention.…”

Direct oral anticoagulants: peri‐operative considerations and controversies

“…Each laboratory should know the sensitivity of their PT and APTT tests to DOACs and be able to advise on their interpretation. Near‐patient viscoelastic tests are often available in the cardiac surgical setting and may detect DOAC activity , though further work is required to better define their utility.…”