Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban
Thrombosis and Haemostasis, 08/10/2012
Marlu R et al. – Some non–specific reversal agents appear to be able to reverse the anticoagulant activity of rivaroxaban or dabigatran. However, clinical evaluation is needed regarding haemorrhagic situations, and a meticulous risk–benefit evaluation regarding their use in this context is required.Methods
- In an ex vivo study, 10 healthy white male subjects were randomised to receive rivaroxaban (20 mg) or dabigatran (150 mg) in one oral administration.
- After a two weeks washout period, they received the other anticoagulant.
- Venous blood samples were collected just before drug administration (H0) and 2 hours thereafter.
- Reversal of anticoagulation was tested in vitro using prothrombin complex concentrate (PCC), rFVIIa or FEIBA at various concentrations.
- Rivaroxaban affects quantitative and kinetic parameters, including the endogenous thrombin potential (ETP–AUC and more pronouncedly the thrombin peak), the lag–time and time to peak.
- PCC strongly corrected ETP–AUC, whereas rFVIIa only modified the kinetic parameters.
- FEIBA corrected all parameters.
- Dabigatran specially affects the kinetics of thrombin generation with prolonged lag–time and time to peak.
- Although PCC increased ETP–AUC, only rFVIIa and FEIBA corrected the altered lag–time.
- For both anticoagulants, lower doses of FEIBA, corresponding to a quarter to half the dose usually used, have potential reversal profile of interest.