Exploring adverse drug reactions associated with the use of direct oral anticoagulants : from greater fundamental knowledge to better clinical prevention

Direct oral anticoagulants (DOAC) are increasingly used in clinical practice, partly due to their higher convenience. However, serious adverse drug reactions (ADR) have been frequently described in DOAC patients, including thrombotic and bleeding events. This interdisciplinary project first demonstrated that prescribing and adherence issues were involved in a significant part of DOAC-related ADR. Contributing factors were explored through qualitative research methods. Then, highly variable DOAC plasma levels were observed in bleeding patients, underlining the usefulness of DOAC measurement for managing reversal or urgent procedures. The performance of an original laboratory assay was evaluated in that context. Finally, several genetic polymorphisms were investigated in vitro, but did not appear to contribute to the inter-individual variability in DOAC levels. These findings pave the way for designing and implementing risk-minimization strategies in order to prevent DOAC-related ADR. Evidence about computerized decision supports for DOAC prescribing was reviewed to this end.