title: 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.
authors.affiliation: RCPAQAP Haematology, St Leonards, Australia. Electronic address: roslyn.bonar@rcpaqap.com.au.
authors.forename: Roslyn
authors.initials: R
authors.lastname: Bonar
authors.affiliation: Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), Pathology West, NSW Health Pathology, Westmead Hospital, Westmead, Australia.
authors.forename: Emmanuel J
authors.initials: EJ
authors.lastname: Favaloro
authors.affiliation: Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), Pathology West, NSW Health Pathology, Westmead Hospital, Westmead, Australia.
authors.forename: Soma
authors.initials: S
authors.lastname: Mohammed
authors.affiliation: Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), Pathology West, NSW Health Pathology, Westmead Hospital, Westmead, Australia.
authors.forename: Monica
authors.initials: M
authors.lastname: Ahuja
authors.affiliation: Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), Pathology West, NSW Health Pathology, Westmead Hospital, Westmead, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pasalic
authors.affiliation: RCPAQAP Haematology, St Leonards, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Sioufi
authors.affiliation: Pathology Services, Royal Hobart Hospital, Hobart, Tas, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Marsden
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D044362:Australasia; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D016903:Drug Monitoring; D065427:Factor Xa Inhibitors / Q000494:pharmacology*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011720:Pyrazoles / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D015203:Reproducibility of Results; D000069552:Rivaroxaban / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D000069552:Rivaroxaban
keywords: Haemostasis; anticoagulants; apixaban; coagulation; laboratory testing; rivaroxaban