Thromb Haemost 2014; 111(02): 240-248
DOI: 10.1160/TH13-06-0470
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays

A multicentre French GEHT study
Isabelle Gouin-Thibault
1  Université Paris Descartes, Sorbonne Paris Cité, INSERM UMR-S765, Paris, France
2  Assistance Publique Hôpitaux de Paris, GH Cochin-Hôtel-Dieu, Service d’Hématologie biologique Paris, France
,
Claire Flaujac
2  Assistance Publique Hôpitaux de Paris, GH Cochin-Hôtel-Dieu, Service d’Hématologie biologique Paris, France
,
Xavier Delavenne
3  Laboratoire de Pharmacologie-Toxicologie, Université Jean Monnet, EA3065, CHU Saint-Etienne, France
,
Sara Quenet
3  Laboratoire de Pharmacologie-Toxicologie, Université Jean Monnet, EA3065, CHU Saint-Etienne, France
,
Marie-Hélenè Horellou
2  Assistance Publique Hôpitaux de Paris, GH Cochin-Hôtel-Dieu, Service d’Hématologie biologique Paris, France
,
Silvy Laporte
3  Laboratoire de Pharmacologie-Toxicologie, Université Jean Monnet, EA3065, CHU Saint-Etienne, France
,
Virginie Siguret
4  Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service d’Hématologie biologique, Paris, France
,
Thomas Lecompte
5  Hopitaux Universitaires de Genève, Hematology, Genève, Switzerland
› Author Affiliations
Financial support:This study was supported by Bristol-Myers Squibb/Pfizer.
Further Information

Publication History

Received: 11 June 2013

Accepted after major revision: 19 September 2013

Publication Date:
27 November 2017 (online)

Summary

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, interlaboratory 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.