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ArticleResearch and practice in thrombosis and haemostasis2025

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.

Geoffrey Foulon-Pinto, Georges Jourdi, Maxime Delrue, Carmelo Lafuente-Lafuente, Candice Cavalie, Isabelle Gouin-Thibault, Julien Le Guen, Pascale Gaussem, Tristan Mirault, Etienne Puymirat and 4 more

Registry-linked trialAbstract read
In one paragraph

Article in Research and practice in thrombosis and haemostasis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02464488 (Study of Interindividual Variability in the Response to New Oral Direct Anticoagulants), which is not on this map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02464488 completednot on this map

Study of Interindividual Variability in the Response to New Oral Direct Anticoagulants (Dabigatran Etexilate, Rivaroxaban or Apixaban) in Patients 80 Years Old and Over, Using a Population Pharmacokinetics Approach.

TypeobservationalSponsorHôpital Charles FoixRan2015 to 2021Enrolled232ConditionsAtrial FibrillationArmsPlasma drug concentrations
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

14 authors.

Geoffrey Foulon-PintoINSERM UMR_S1140, Université Paris Cité, Paris, France.
Georges JourdiINSERM UMR_S1140, Université Paris Cité, Paris, France.
Maxime DelrueINSERM UMR_S1140, Université Paris Cité, Paris, France.
Carmelo Lafuente-LafuenteGH Pitié Salpêtrière-Charles Foix-Gériatrie à orientation cardiologique et neurologique, Sorbonne Université, Ivry-sur-Seine, France.
Candice CavalieINSERM UMR_S1140, Université Paris Cité, Paris, France.
Isabelle Gouin-ThibaultService d'Hématologie Biologique, CHU de Rennes, Rennes, France.
Julien Le GuenGériatrie aiguë, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
Pascale GaussemINSERM UMR_S1140, Université Paris Cité, Paris, France.
Tristan MiraultMédecine vasculaire, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, INSERM U970 PARCC team 5, Université Paris Cité, Paris, France.
Etienne PuymiratCardiologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
Thomas LecompteService d'Hématologie Biologique, CHU de Rennes, Rennes, France.
Eric PautasINSERM UMR_S1140, Université Paris Cité, Paris, France.
Emmanuel CurisHématologie Biologique, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France.
Virginie SiguretINSERM UMR_S1140, Université Paris Cité, Paris, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

atrial fibrillationdirect oral anticoagulantelderlyfibrin formationpharmacodynamicsthrombin generation

Identifiers

PMID40821748
PMCPMC12351382

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.