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.

Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.