Global thromboelastometry in patients receiving direct oral anticoagulants: the RO-DOA study
Rapidly available tests might be useful to measure the anticoagulant effect of direct oral anticoagulants (DOAs) in emergency situations as bleedings, surgery, or before thrombolysis. The aim of this study was to assess the effects of DOAs on global thromboelastometry (ROTEM). Coagulation parameters assessed at peak and trough in patients with non-valvular atrial fibrillation receiving apixaban, dabigatran or rivaroxaban at steady-state (patients) were compared to those of healthy volunteers (controls). Citrated blood samples were tested by ROTEM using diluted EXTEM assay, with and without the addition of an anti-FXa catcher, and using ECATEM-B, with and without the addition of an anti-FIIa catcher. Overall 30 patients (10 for each DOA) and 15 controls were included. The mean clotting time (CT) of patients at peak and trough were significantly higher compared to controls. The mean CT was significantly shortened after the addition of the anti-FXa catcher to apixaban (p = 0.005 for peak and p = 0.009 for trough) and to rivaroxaban samples (p = 0.005 for both peak and trough) and after the addition of anti-FIIa cather to dabigatran samples (p = 0.005 for both peak and trough). ROC curve analyses showed a good accuracy for CT and for CT/CT + catcher (CTc) in measuring dabigatran anticoagulant activity (AUC 1.000 and 0.993, respectively); for CT, CT/CTc and clot formation time (CFT)/CFT + catcher (CFTc) in measuring both apixaban activity (0.917, 0.880 and 0.880, respectively) and rivaroxaban activity (0.973, 0.987 and 0.860, respectively). In this study the use of ad-hoc designed reagents and catcher molecules was able to accurately identify DOAs activity at ROTEM.
KeywordsAnticoagulants Apixaban Dabigatran Emergencies Rivaroxaban Thrombelastography
We thank Tem Innovations GmbH for providing reagents free of charge.
Compliance with ethical standards
Conflict of interest
G.A. reports consulting fees from Bayer, Boehringer Ingelheim, and Daiichi Sankyo, lecture fees from Bristol-Myers Squibb and Sanofi-Aventis. C.B. reports lecture fees from Boehringer Ingelheim, Daiichi Sankyo and Bristol-Myers Squibb. M.C.V., M.G.M. and F.I. have no disclosures.
- 3.Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, Haeusler KG, Oldgren J, Reinecke H, Roldan-Schilling V, Rowell N, Sinnaeve P, Collins R, Camm AJ, Heidbüchel H, ESC Scientific Document Group (2018) The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 39:1330–1393CrossRefGoogle Scholar
- 11.Samama MM, Contant G, Spiro TE, Perzborn E, Guinet C, Gourmelin Y et al (2012) Rivaroxaban Anti-Factor Xa Chromogenic Assay Field Trial Laboratories: evaluation of the anti-factor Xa chromogenic assay for the measurement of rivaroxaban plasma concentrations using calibrators and controls. Thromb Haemost 107:379–387CrossRefGoogle Scholar
- 16.Schöchl H, Nienaber U, Hofer G, Voelckel W, Jambor C, Scharbert G et al (2010) Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care 14(2):R55CrossRefGoogle Scholar
- 25.Lippi G, Favaloro EJ (2015) Recent guidelines and recommendations for laboratory assessment of the direct oral anticoagulants (DOACs): is there consensus? Clin Chem Lab Med 53:185–197Google Scholar
- 28.Pernod G, Albaladejo P, Godier A, Samama CM, Susen S, Gruel Y et al (2013) Working Group on Perioperative Haemostasis. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: proposals of the working group on perioperative haemostasis (GIHP)—March 2013. Arch Cardiovasc Dis 106:382–393CrossRefGoogle Scholar
- 33.Oswald E, Velik-Salchner C, Innerhofer P et al (2015) Results of rotational thromboelastometry, coagulation activation markers and thrombin generation assays in orthopedic patients during thromboprophylaxis with rivaroxaban and enoxaparin: a prospective cohort study. Blood Coagul Fibrinolysis 26:136–144CrossRefGoogle Scholar
- 37.Bliden KP, Chaudhary R, Mohammed N, Muresan AA, Lopez-Espina CG, Cohen E, Raviv G, Doubleday M, Zaman F, Mathew B, Tantry US, Gurbel PA (2017) Determination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system. J Thromb Thrombolysis 43:437–445CrossRefGoogle Scholar
- 39.Ruiz Ortiz M, Muñiz J, Raña Míguez P, Roldán I, Marín F, Asunción Esteve-Pastor M, Cequier A, Martínez-Sellés M, Bertomeu V, Anguita M, FANTASIIA Study Investigators (2018) Inappropriate doses of direct oral anticoagulants in real-world clinical practice: prevalence and associated factors. A subanalysis of the FANTASIIA Registry. Europace 20:1577–1583CrossRefGoogle Scholar