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Characterisation of direct acting oral anticoagulants and their pharmacodynamics on thrombin generation and coagulation parameters

Halliday, Matthew (2017) Characterisation of direct acting oral anticoagulants and their pharmacodynamics on thrombin generation and coagulation parameters. Honours thesis, Murdoch University.

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Introduction: Vitamin K antagonists (VKA) are historically used to treat thrombosis but newer direct acting oral anticoagulants (DOAC) have been released. DOACs influence laboratory methods that monitor haemostasis, leading to false positives and prolonged clotting results. Trough DOAC concentrations may have less influence at than at peak, but this is unknown. There is speculation that obesity also affects DOAC efficiency. This study sought to validate the effects of two common DOACs, rivaroxaban and apixaban, on 12 laboratory assays at peak and trough concentrations, as well as the influence of obesity on the drugs and assays. Methods: Rivaroxaban (n=20) and apixaban (n=21) patients had samples collected immediately before their next dose, and 3 hours after to provide peak and trough. Healthy controls (n=20) provided a sample at one-time point. Relevant medical histories and demographics, including BMI, were collected after obtaining informed consent. Samples underwent coagulation and thrombophilia panels as well as thrombin antithrombin complex, prothrombin fragments 1+2, and thrombin generation assays (TGA). Statistical analysis was performed between peak and controls, peak and trough, and all BMI groups. Results: Significant prolongations were found with the prothrombin time (PT), activated partial thromboplastin time (APTT), TGA, and false positives for the dilute Russell viper venom time (DRVVT) by both rivaroxaban and apixaban. Apixaban was less potent than rivaroxaban with significant differences only between peak and trough for PT, and APTT. Only two results were influenced by weight; the APTT with rivaroxaban and free protein S for the controls. Conclusion: Rivaroxaban and apixaban are similar drugs but impact the assays differently due to dosage, half-life, and rate activity. Both influence assays more at peak than trough, but trough is still notably influenced compared to the controls. This study highlights the influence of these drugs on most tests performed in a haemostasis laboratory.

Item Type: Thesis (Honours)
Murdoch Affiliation(s): School of Veterinary and Life Sciences
Supervisor(s): Gilmore, Grace and Hughes, Quintin
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