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

Yvonne M C Henskens,Simon Schalla,Hugo Ten Cate,Paul Verhezen,Arina Ten Cate-Hoek,René Van Oerle,Anouk J W Gulpen,Harry J Crijns,Henri Spronk,Rick Wetzels

doi:10.1186/s12959-017-0160-2

Yvonne M C Henskens, Simon Schalla + Show 8 more

Open Access

https://doi.org/10.1186/s12959-017-0160-2

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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).

Highlights

Traditional coagulation tests are included in emergency guidelines for management of patients on direct oral anticoagulants (DOACs) who experience acute bleeding or require surgery
Rivaroxaban was accurately detected by prothrombin time (PT) Neoplastin (98%) and less so by Activated Partial Thromboplastin Time (APTT) Cephascreen (85%)
In patients with non-valvular atrial fibrillation (NVAF), the ability of routine coagulation tests to detect the presence of significant levels of DOACs is test and reagent dependent

Summary

Introduction

Traditional 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. With the introduction of direct oral anticoagulants it was emphasized that no routine laboratory testing would be needed [2,3,4,5,6,7]. In emergency situations the need for testing remains since residual activity of the anticoagulant treatment might introduce e.g. bleeding during surgery. Screening tests for detecting anticoagulants, which can be performed 24 h a day instead of just during working hours should be available to guide treatment decisions. The concentration below 30 ng/mL is proposed as a safe-for surgical treatment threshold [8]

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