PB0034 - Assessment of fibrinography and thrombography variability using Thrombodynamics-4D in patients ≥ 80 years receiving DOAC (rivaroxaban, apixaban, dabigatran) for atrial fibrillation

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

GF

Geoffrey Foulon-Pinto

Pharm, PhD
Université Paris Cité, Inserm UMR-S 1140, Hématologie biologique, Hôpital Lariboisière (AP-HP)
Paris, Ile-de-France, France
Georges Jourdi, PharmD, PhD

Associate Professor in haematology
Inserm Research institute
Paris, Ile-de-France, France
CL

Carmelo Lafuente-Lafuente

MD
Sorbonne Université, Service de Gériatrie, Hôpital Charles Foix (AP-HP), CEpiA Team (Clinical Epidemiology and Ageing), University Paris Est Créteil, INSERM, IMRB, Créteil.
Ivry-sur-Seine, Ile-de-France, France
JL

Julien Le Guen

MD
Service de Gériatrie, Hôpital Européen Georges Pompidou (AP-HP)
Paris, Ile-de-France, France
MD

Maxime Delrue

MD, PhD
Université Paris Cité, Hématologie biologique, Hôpital Lariboisière (AP-HP)
Paris, Ile-de-France, France
LR

Léa Rivière

MD
Service de Gériatrie, Hôpital Lariboisière (AP-HP)
Paris, Ile-de-France, France
Isabelle Gouin Thibault

PhD - PharmD
Laboratoire d'Hématology, Pontchaillou University Hospital of Rennes, IRSET-INSERM-1085, Univ Rennes, France.
Rennes, Bretagne, France
TL

Thomas Lecompte

MD, PhD
Université de Lorraine, Faculté de médecine de Nancy
Nancy, Ile-de-France, France
PG

Pascale Gaussem

PharmD, PhD
Université Paris Cité, Inserm UMR-S1140, Hôpital Européen Georges Pompidou
Paris, Ile-de-France, France
EP

Eric Pautas

MD, PhD
Sorbonne Université, Unité de Gériatrie aiguë, Hôpital Charles Foix (AP-HP), INSERM UMR-S-1140, Paris
Ivry-sur-Seine, Ile-de-France, France
EC

Emmanuel Curis, PhD PharmD

Pharm, PhD
Université Paris Cité, UR 7537 BioSTM (Biostatistics), Hématologie biologique, Hôpital Lariboisière (AP-HP)
Paris, Ile-de-France, France

Presenting Author(s)

Virginie Siguret

PharmD, PhD
Université Paris Cité, Inserm UMR-S 1140, Hématologie biologique, Hôpital Lariboisière (AP-HP)
Paris, Ile-de-France, France

Background: Scarce data are available on fibrinography/thrombography parameters in very elderly patients receiving DOAC for atrial fibrillation (AF), who are often polymedicated and have numerous co-morbidities. Thrombodynamics-4D (TD-4D) assay simultaneously assesses fibrin clot formation and thrombin generation in plasma.

Aims: i/to determine whether TD-4D is a reliable system for assessing DOAC pharmacodynamics (PD) in elderly patients with AF; ii/to identify factors influencing inter-individual variability of DOAC PD, particularly at trough levels.

Methods: ADAGE-NCT02464488 was a prospective multicentre academic study, including in-patients aged ≥ 80-years, receiving a DOAC for AF since at least 4 days. Each patient had 1 to 5 samples taken at different times over a 20-day period. Fibrinography and thrombography parameters were measured using TD-4D in addition to DOAC plasma levels.

Results: 342 samples from 185 ADAGE patients (mean age 86±4 years, 69.2% females) were analysed: 67-rivaroxaban patients, 70-apixaban and 48-dabigatran, most receiving a reduced dose. All three DOACs prolonged fibrinography lag time, and decreased the initial rate of clot-growth and clot size at 30 min in a concentration-dependent manner (Fig. 1). In contrast, clot density was not related to DOAC level. Similarly, DOAC significantly prolonged thrombography temporal parameters, while decreasing the maximal-thrombin-peak (Cmax_ATG) and the endogenous-thrombin-potential (Fig. 2). DOAC levels contributed significantly to explain inter-individual variability of the initial rate of clot-growth at Tmin irrespective of DOAC (p < 0.003), as well as amiodarone for rivaroxaban (p < 0.002). In addition, we identified DOAC levels as a significant contributor to explain Cmax_ATG inter-individual variability at Tmin for the 3 DOACs, as well as CYP-inhibitor use and the presence of heart failure in patients taking rivaroxaban.

Conclusion(s): Fibrinography and thrombography assessed using TD-4D provide accurate results, evidencing, for the first time, the interest of this system for evaluating DOAC PD in ≥ 80-year patients.