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The effect of the direct factor Xa inhibitors apixaban and rivaroxaban on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples.

Abstract
The direct oral anticoagulants (DOACs), now including dabigatran, apixaban and rivaroxaban, have given clinicians alternative options to low molecular weight heparins (LMWHs) and vitamin K antagonist therapy, including warfarin, for the treatment of atrial fibrillation and treatment and prevention of venous thromboembolic (VTE) disease. DOACs have been successfully marketed as not requiring monitoring; however, there will be situations where clinicians will request laboratory testing, including emergency department admissions for haemorrhage or thrombosis, or emergency surgical interventions. We report the results of several Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) surveys using apixaban and rivaroxaban spiked samples to either assess the suitability of certain potential screening or drug-quantifying assays, for assessment of drug presence or absence or measurement of levels, as well as assessing potential interference in a wide variety of haemostasis assays. We also include additional evaluations using ex vivo samples from patients given apixaban and rivaroxaban for various therapeutic reasons. The prothrombin time (PT) and activated partial thromboplastin time (APTT) show better sensitivity with rivaroxaban than apixaban. Anti-Xa assays show good concordance and reproducibility with expected drug levels; however, availability of these assays may be limited to larger institutions. Interference of apixaban and rivaroxaban on haemostasis testing extends beyond routine coagulation assays to encompass a plethora of specialised assays, including factor assays, lupus inhibitor, and FVIII inhibitor estimation. In conclusion, this report highlights the influence of these drugs on most tests performed in haemostasis laboratories, and the potential for some tests to predict the presence, absence or level of these drugs in plasma.
AuthorsRoslyn Bonar, Emmanuel J Favaloro, Soma Mohammed, Monica Ahuja, Leonardo Pasalic, John Sioufi, Katherine Marsden
JournalPathology (Pathology) Vol. 48 Issue 1 Pg. 60-71 (Jan 2016) ISSN: 1465-3931 [Electronic] England
PMID27020211 (Publication Type: Evaluation Study, Journal Article)
CopyrightCopyright © 2015 The Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Anticoagulants
  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban
Topics
  • Anticoagulants (pharmacology)
  • Australasia
  • Blood Coagulation (drug effects)
  • Blood Coagulation Tests
  • Drug Monitoring
  • Factor Xa Inhibitors (pharmacology)
  • Hemostasis (drug effects)
  • Humans
  • Partial Thromboplastin Time
  • Prothrombin Time
  • Pyrazoles (pharmacology)
  • Pyridones (pharmacology)
  • Reproducibility of Results
  • Rivaroxaban (pharmacology)

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