Browse by author
Lookup NU author(s): Dr Emma KampourakiORCiD, Dr Salah Abohelaika, Dr Peter Avery, Dr Tina Biss, Dr Hilary Wynne, Professor Farhad Kamali
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2020, The Author(s).According to both trial and clinical data on direct oral anticoagulants (DOACs) elderly patients are at greatest risk of bleeding. It is unclear whether age intrinsically affects anticoagulation response. To investigate the age-related sensitivity to DOACs, we compared the pharmacological activity of the direct factor Xa inhibitor, rivaroxaban, between young and elderly subjects ex-vivo. 36 fit elderly and 30 fit young subjects [median (IQR) age: 83(75–87) vs 30(26–38) years] provided a blood sample. Clotting parameters were measured in the resultant plasma samples incubated with rivaroxaban (100–500 ng/ml). Parametric, non-parametric tests and regression lines adjusted for rivaroxaban concentration and baseline values were used to compare data. Rivaroxaban produced a greater prolongation of both Prothrombin Time (PT) and modified Prothrombin Time (mPT) (both p < 0.001) in the elderly compared to young subjects (with difference in mean PT increasing from 1.6 to 6.1s and for mPT from 23.5 to 71.1s at 100 ng/ml and 500 ng/ml plasma rivaroxaban concentration, respectively). Factor X and factor II activity was significantly lower in the elderly in the presence of rivaroxaban (p < 0.001 for both). Rivaroxaban prolonged time-based parameters and suppressed the amount of thrombin generation to a significantly greater extent in the elderly compared to young subjects [%change from baseline for Endogenous Thrombin Potential (ETP): − 35.0 ± 4.4 vs − 29.8 ± 7.4 nM*min; p = 0.002]. The use of validated DOAC assays will be of considerable benefit for monitoring elderly patients who, because of their increased sensitivity to rivaroxaban, may require lower doses of the drug for therapeutic anticoagulation.
Author(s): Kampouraki E, Abohelaika S, Avery P, Biss T, Murphy P, Wynne H, Kamali F
Publication type: Article
Publication status: Published
Journal: Journal of Thrombosis and Thrombolysis
Year: 2021
Volume: 52
Pages: 170-178
Print publication date: 01/07/2021
Online publication date: 01/11/2020
Acceptance date: 26/10/2020
Date deposited: 23/06/2022
ISSN (print): 0929-5305
ISSN (electronic): 1573-742X
Publisher: Springer
URL: https://doi.org/10.1007/s11239-020-02326-x
DOI: 10.1007/s11239-020-02326-x
Altmetrics provided by Altmetric
