title: Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays. A multicentre French GEHT study.
abstract: While laboratory monitoring is not required in patients treated with apixaban, a direct factor-Xa inhibitor, assessment of its concentration is useful in some critical situations. However, few data are available on its effect on coagulation tests and on the suitability of anti-Xa assays for its quantification. It was the objective of this study to identify laboratory tests suitable for apixaban concentration assessment. Coagulation tests - PT and aPTT- and anti-Xa assays were performed in apixaban-spiked plasma samples. To evaluate the sensitivity of PT and aPTT to apixaban, we conducted a first monocenter part, with a wide range of concentrations (50-1,000 ng/ml), a large panel of reagents (20 reagents), and two coagulometers (STAR®, Stago and ACL TOP®, IL), and a second multicenter part involving 13 laboratories using either a common PT reagent (RecombiPlastin2G®) or the local PT and aPTT reagents. In the multicentre part, five blinded apixaban-spiked plasma samples (0/100/200/400/800 ng/ml - checked by HPLC-MS/MS) were used; apixaban concentrations were measured with three anti-Xa assays, apixaban calibrators and controls (Stago). PT and aPTT tests using a large panel of reagents displayed a low sensitivity to a wide range of apixaban concentrations. The concentrations to double PT ranged from 400 to >1,000 ng/ml with the 10 reagents. With the three anti-Xa assays, inter-laboratory precision and accuracy were below 11% and 12%, respectively. In conclusion, whereas PT and aPTT tests were not sensitive enough to detect apixaban, the three anti-Xa assays tested using lyophilised apixaban calibrators and controls allowed to reliably quantify a wide range of apixaban concentrations.
authors.affiliation: Isabelle Gouin Thibault, Laboratoire d'Hématologie, Groupe Hospitalier Cochin-Hôtel Dieu, 27, rue du Faubourg Saint-Jacques, 75 679 Paris Cedex 14, France, Tel.: +33 1 42 34 84 47, Fax: +33 1 58 41 19 97, E-mail: isabelle.gouin@htd.aphp.fr.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gouin-Thibault
authors.forename: Claire
authors.initials: C
authors.lastname: Flaujac
authors.forename: Xavier
authors.initials: X
authors.lastname: Delavenne
authors.forename: Sara
authors.initials: S
authors.lastname: Quenet
authors.forename: Marie-Hélenè
authors.initials: MH
authors.lastname: Horellou
authors.forename: Silvy
authors.initials: S
authors.lastname: Laporte
authors.forename: V
authors.initials: V
authors.lastname: Siguret
authors.forename: T
authors.initials: T
authors.lastname: Lecompte
mesh_terms: D000925:Anticoagulants / Q000097:blood*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000592:standards; D016903:Drug Monitoring / Q000379:methods* / Q000592:standards; D005165:Factor V / Q000378:metabolism; D065427:Factor Xa Inhibitors; D005602:France; D006801:Humans; D059021:Laboratory Proficiency Testing; D015588:Observer Variation; D010314:Partial Thromboplastin Time; D011237:Predictive Value of Tests; D011516:Prothrombin / Q000378:metabolism; D011517:Prothrombin Time; D011720:Pyrazoles / Q000097:blood*; D011728:Pyridones / Q000097:blood*; D012015:Reference Standards; D015203:Reproducibility of Results
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D005165:Factor V; D011516:Prothrombin
keywords: Apixaban; anti-Xa; anticoagulant agents; blood coagulation tests; multicenter study