Modified ROTEM for the detection of rivaroxaban and apixaban anticoagulant activity in whole blood
BACKGROUND Rapid detection of the anticoagulant effect of oral factor Xa (FXa) inhibitors may be essential in several emergency clinical situations. Specific assays quantifying the drugs are performed in plasma and require a turnaround time that is too long to be useful in emergency situations. Rotational thromboelastometry (ROTEM) is a whole blood coagulation assay of blood viscoelasticity and could be of interest for FXa inhibitor detection in emergency. However, conventional ROTEM reagents only detect high amounts of inhibitors. OBJECTIVE The aim of this study was first to assess the effect of whole blood components on the viscoelastic measurement of the effects of FXa inhibitors, an second to evaluate whether a modified ROTEM, triggered with a low amount of tissue factor and a saturating amount of phospholipid vesicles, can reliably detect low levels of FXa inhibitor activity in whole blood. DESIGN Diagnostic test study. SETTINGS A university research laboratory. From November 2014 to April 2016. PATIENTS Sixty-six patients: 30 treated with rivaroxaban, 17 with apixaban and 19 without treatment. INTERVENTION ROTEM was triggered with 2.5 pmol l−1 of tissue factor and 10 μmol l−1 of phospholipid vesicles. MAIN OUTCOME MEASURES Modified ROTEM parameters were measured in different experimental conditions: platelet-poor plasma (PPP), platelet-rich plasma, PPP supplemented with fibrinogen and reconstituted whole blood with various haematocrit levels adjusted between 30 and 60%. Modified ROTEM was further validated using whole blood from patients who were either treated or not treated with FXa inhibitors. RESULTS Modified ROTEM allowed detection of as little as 25 ng ml−1 FXa inhibitors in PPP, with at least a 1.4-fold increase of the clotting time (P ≤ 0.02). Neither changes of fibrinogen concentration nor variations of platelet count or haematocrit precluded FXa inhibitor detection. A lengthened modified ROTEM clotting time of more than 197 s allowed detection of FXa inhibitor concentrations above 30 ng ml−1 in whole blood with 90% sensitivity and 85% specificity. CONCLUSION Modified ROTEM may be applicable in emergency situations for the detection of FXa inhibitors in whole blood. Correspondence to Charles M. Samama, MD, PhD, FCCP, Department of Anaesthesia and Intensive Care Medicine, Cochin University Hospital, 27 rue du Faubourg St Jacques, 75014 Paris, France Tel: +33 1 42 34 85 51/+33 6 62 14 86 64; fax: +33 1 58 41 14 15; e-mail: marc.samama@aphp.fr Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.ejanaesthesiology.com). © 2019 European Society of Anaesthesiology
BACKGROUND Rapid detection of the anticoagulant effect of oral factor Xa (FXa) inhibitors may be essential in several emergency clinical situations. Specific assays quantifying the drugs are performed in plasma and require a turnaround time that is too long to be useful in emergency situations. Rotational thromboelastometry (ROTEM) is a whole blood coagulation assay of blood viscoelasticity and could be of interest for FXa inhibitor detection in emergency. However, conventional ROTEM reagents only detect high amounts of inhibitors. OBJECTIVE The aim of this study was first to assess the effect of whole blood components on the viscoelastic measurement of the effects of FXa inhibitors, an second to evaluate whether a modified ROTEM, triggered with a low amount of tissue factor and a saturating amount of phospholipid vesicles, can reliably detect low levels of FXa inhibitor activity in whole blood. DESIGN Diagnostic test study. SETTINGS A university research laboratory. From November 2014 to April 2016. PATIENTS Sixty-six patients: 30 treated with rivaroxaban, 17 with apixaban and 19 without treatment. INTERVENTION ROTEM was triggered with 2.5 pmol l−1 of tissue factor and 10 μmol l−1 of phospholipid vesicles. MAIN OUTCOME MEASURES Modified ROTEM parameters were measured in different experimental conditions: platelet-poor plasma (PPP), platelet-rich plasma, PPP supplemented with fibrinogen and reconstituted whole blood with various haematocrit levels adjusted between 30 and 60%. Modified ROTEM was further validated using whole blood from patients who were either treated or not treated with FXa inhibitors. RESULTS Modified ROTEM allowed detection of as little as 25 ng ml−1 FXa inhibitors in PPP, with at least a 1.4-fold increase of the clotting time (P ≤ 0.02). Neither changes of fibrinogen concentration nor variations of platelet count or haematocrit precluded FXa inhibitor detection. A lengthened modified ROTEM clotting time of more than 197 s allowed detection of FXa inhibitor concentrations above 30 ng ml−1 in whole blood with 90% sensitivity and 85% specificity. CONCLUSION Modified ROTEM may be applicable in emergency situations for the detection of FXa inhibitors in whole blood. Correspondence to Charles M. Samama, MD, PhD, FCCP, Department of Anaesthesia and Intensive Care Medicine, Cochin University Hospital, 27 rue du Faubourg St Jacques, 75014 Paris, France Tel: +33 1 42 34 85 51/+33 6 62 14 86 64; fax: +33 1 58 41 14 15; e-mail: marc.samama@aphp.fr Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.ejanaesthesiology.com). © 2019 European Society of Anaesthesiology
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