# Fibrinography and thrombography (thrombodynamics-4D) in atrial fibrillation assessment of direct oral anticoagulants in geriatrics patients aged 80 years and older receiving direct oral anticoagulant therapy

## TL;DR

This study evaluates how well fibrinography and thrombography can assess the effects of direct oral anticoagulants in elderly patients with atrial fibrillation.

## Contribution

The study introduces the use of thrombodynamics-4D to assess pharmacodynamic variability of DOACs in patients aged 80 and older.

## Key findings

- DOACs prolonged fibrinography lag time and decreased clot growth in a concentration-dependent manner.
- Apixaban and dabigatran concentrations were significant predictors of pharmacodynamic variability.
- Cardiac failure influenced thrombin peak height variability in rivaroxaban patients.

## Abstract

Scarce data are available on pharmacodynamic (PD) variability in very elderly patients receiving direct oral anticoagulants (DOACs) for atrial fibrillation (AF). Thrombodynamics-4D (TD-4D), which simultaneously assesses fibrin clot formation and thrombin generation, has not yet been tested in patients on rivaroxaban, apixaban, or dabigatran.

To (i) evaluate TD-4D’s ability to assess DOAC effect added to normal plasma; (ii) assess DOAC PD in very elderly patients with AF along with DOAC concentrations; (iii) identify factors associated with interindividual variability of DOAC PD at peak and trough levels.

Assessment of Direct oral Anticoagulants in Geriatrics (NCT02464488) is a prospective, multicenter study including inpatients aged ≥80 years receiving DOACs for AF for at least 4 days. Fibrinography and thrombography parameters were measured using TD-4D along with plasma DOAC concentrations (antifactor [F]Xa or anti-FIIa activity) and fibrinogen.

We analyzed pooled normal plasma samples spiked with DOACs and 345 samples from 187 Assessment of Direct oral Anticoagulants in Geriatrics patients (mean ± SD, age 87 ± 4 years; 69% females): 69 on rivaroxaban, 70 on apixaban, and 48 on dabigatran. All 3 DOACs prolonged fibrinography lag time and decreased initial rate of clot growth and clot size at 30 minutes in a concentration-dependent manner in spiking experiments and patients. DOACs prolonged temporal thrombography parameters while decreasing thrombin peak height and endogenous thrombin potential. At trough, apixaban and dabigatran concentrations were the only significant predictors of interindividual variability in both thrombin peak height (thrombography) and initial rate of clot growth (fibrinography). In rivaroxaban patients, cardiac failure significantly influenced thrombin peak height variability.

Fibrinography and thrombography, assessed simultaneously with TD-4D, provided consistent results for all 3 DOACs, including dabigatran. Substantial PD variability was observed, partly influenced by DOAC concentrations. The clinical relevance of such variability remains to be demonstrated.

•Data on PD variability in very elderly patients on DOACs are scarce.•We assessed thrombography/fibrinography (Thrombodynamics) in patients ≥80 years old, along with DOAC levels.•DOACs, including dabigatran, exerted a significant concentration-dependent effect on most thrombography/fibrinography parameters.•Substantial PD variability was observed, partly influenced by DOAC concentrations.

Data on PD variability in very elderly patients on DOACs are scarce.

We assessed thrombography/fibrinography (Thrombodynamics) in patients ≥80 years old, along with DOAC levels.

DOACs, including dabigatran, exerted a significant concentration-dependent effect on most thrombography/fibrinography parameters.

Substantial PD variability was observed, partly influenced by DOAC concentrations.