Stability of Rivaroxaban and Apixaban Anti-Xa Activities in Whole Blood Samples: A French Bicentric Study

Over the last 10 years, the use of direct oral anticoagulants (DOACs) in the management of venous thromboembolism and atrial fibrillation grew significantly, and in particular direct factor Xa inhibitors rivaroxaban and apixaban. Clinical trials of these molecules did not underline the necessity of systematic laboratory monitoring, and the measurement of anti-Xa activity was only indicated in urgent situations such as trauma or prior to acute surgery.[1] [2] [3] [4] However, in 2021, the International Council for Standardization in Haematology (ICSH) updated these recommendations and added several nonurgent indications for anti-Xa activity measurement: advanced age, severe renal failure, ahead of a surgical procedure at high bleeding risk, body mass index >40 kg/m², and drug interactions.[5] [6] The 2018 ICSH recommendations stated that citrated whole blood samples for anti-Xa activity measurement should be processed within 4 hours of collection, but without providing evidence. Moreover, the French Working Group on Hemostasis and Thrombosis recommendations indicated a shorter stability, of 2 hours, in accordance with the only study then published in the literature.[7] [8] [9] In practice, some laboratories may find it difficult to comply with these short delays.

The aim of this study, performed in two French hospitals using different techniques, was to evaluate the stabilities of rivaroxaban and apixaban anti-Xa activities in whole blood samples stored at room temperature for up to 6 hours after collection, in the context of routine clinical laboratory testing.

Publication History

Article published online:
15 February 2023

• References

• 1 Chan N, Sobieraj-Teague M, Eikelboom JW. Direct oral anticoagulants: evidence and unresolved issues. Lancet 2020; 396 (10264): 1767-1776
• 2 Martin KA, Beyer-Westendorf J, Davidson BL, Huisman MV, Sandset PM, Moll S. Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation. J Thromb Haemost 2021; 19 (08) 1874-1882
• 3 Samuelson BT, Cuker A, Siegal DM, Crowther M, Garcia DA. Laboratory assessment of the anticoagulant activity of direct oral anticoagulants: a systematic review. Chest 2017; 151 (01) 127-138
• 4 Kitchen S, Gray E, Mackie I, Baglin T, Makris M. BCSH committee. Measurement of non-coumarin anticoagulants and their effects on tests of haemostasis: guidance from the British Committee for Standards in Haematology. Br J Haematol 2014; 166 (06) 830-841
• 5 Douxfils J, Adcock DM, Bates SM. et al. 2021 Update of the International Council for Standardization in Haematology recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost 2021; 121 (08) 1008-1020
• 6 Weber J, Olyaei A, Shatzel J. The efficacy and safety of direct oral anticoagulants in patients with chronic renal insufficiency: a review of the literature. Eur J Haematol 2019; 102 (04) 312-318
• 7 Groupe d'études sur l'Hémostase et la Thrombose (GFHT). [Recommandations pré-analytiques en hémostase: Stabilité des paramètres d'hémostase spécialisée et délais de réalisation des examens (partie 2)] [Internet]. [Paris]: GFHT; 2018 [cited 2022 Jul 29]. Available at: https://site.geht.org/
• 8 Gosselin RC, Adcock DM, Bates SM. et al. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost 2018; 118 (03) 437-450
• 9 McGrail R, Revsholm J, Nissen PH, Grove EL, Hvas AM. Stability of direct oral anticoagulants in whole blood and plasma from patients in steady state treatment. Thromb Res 2016; 148: 107-110
• 10 Boissier E, Genebrier S, Lakhal K. et al. Rivaroxaban and apixaban anti-Xa measurements: impact of plasma storage for 7 days at room temperature. Thromb Haemost 2018; 118 (08) 1488-1490
• 11 Godier A, Dincq AS, Martin AC. et al. Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study. Eur Heart J 2017; 38 (31) 2431-2439
• 12 Thuile K, Giacomuzzi K, Jani E, Marschang P, Mueller T. Evaluation of the in vitro stability of direct oral anticoagulants in blood samples under different storage conditions. Scand J Clin Lab Invest 2021; 81 (06) 461-468