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.
One 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.
Dabigatran, ≥ 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.
In 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.
The Institutional Review Board of the MUMC approved this study (December 2011, project number 114069).
van den Besselaar AM. Standardization of the prothrombin time in oral anticoagulant control. Haemostasis. 1985;15(4):271–7. PubMed
Agency EM. Pradaxa [dabigatran etexilate], product information. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000829/WC500041059.pdf. Accessed 28 september 2015.
Agency EM. Xarelto [rivaroxaban], product information. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000944/WC500057108.pdf. Accessed 17 July 2015.
Agency EM. Eliquis [apixaban], product information. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf Accessed 29 October 2015.
Agency EM. Lixiana [edoxaban], product information.. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002629/WC500189045.pdf. Accessed 3 July 2015.
Funk DM. Coagulation assays and anticoagulant monitoring. Hematology Am Soc Hematol Educ Program. 2012;2012:460–5. PubMed
Baglin T, Keeling D, Kitchen S. British Committee for Standards in H. Effects on routine coagulation screens and assessment of anticoagulant intensity in patients taking oral dabigatran or rivaroxaban: guidance from the British Committee for Standards in Haematology. Br J Haematol. 2012;159(4):427–9. CrossRefPubMed
Specialisten. WNvdwveOvM. Leidraad voor begeleide introductie nieuwe orale antistollingsmiddelen. 2012; https://cvgk.nl/2013/01/04/leidraad-begeleide-introductie-noacs/.
Lessire S, Douxfils J, Pochet L, et al. Estimation of rivaroxaban plasma concentrations in the perioperative setting in patients with or without heparin bridging. Clin Appl Thromb Hemost. 2016:1076029616675968.
Seyve L, Richarme C, Polack B, Marlu R. Impact of four direct oral anticoagulants on rotational thromboelastometry (ROTEM). Int J Lab Hematol. 2017;
Gous T, Couchman L, Patel JP, Paradzai C, Arya R, Flanagan RJ. Measurement of the direct oral anticoagulants apixaban, dabigatran, edoxaban, and rivaroxaban in human plasma using turbulent flow liquid chromatography with high-resolution mass spectrometry. Ther Drug Monit. 2014;36(5):597–605. CrossRefPubMed
- 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
Anouk J. W. Gulpen
René van Oerle
Harry J. Crijns
Hugo ten Cate
Arina ten Cate-Hoek
- BioMed Central
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