Urgent Need to Measure Effects of Direct Oral Anticoagulants
Notice bibliographique
Résumé
anticoagulantT he direct oral anticoagulants (DOACs), which include dabigatran, rivaroxaban, apixaban, and edoxaban, were designed to be given in fixed doses without routine coagulation monitoring.When administered in this manner in trials that included >71 000 patients with atrial fibrillation 1 and >27 000 patients with venous thromboembolism, 2 the DOACs were at least as effective as vitamin K antagonists but were associated with less serious bleeding, particularly less intracranial bleeding.Eliminating coagulation monitoring simplifies anticoagulation therapy.This feature, together with their proven efficacy and safety, explains why guidelines give preference to the DOACs over vitamin K antagonists for stroke prevention in atrial fibrillation and for the treatment of venous thromboembolism.Although routine coagulation monitoring is unnecessary, there is an urgent need for readily and rapidly available tests to measure the DOACs.This need will increase with the introduction of costly reversal agents such as idarucizumab for dabigatran 3 and andexanet alfa for rivaroxaban, apixaban, and edoxaban. 4Idarucizumab is already licensed, and andexanet is undergoing regulatory review and could be approved later this year.What tests are currently available, and why do we need new ones?Although currently available global tests of coagulation such as the activated partial thromboplastin time (aPTT) and prothrombin time (PT) can be useful to assess the anticoagulant effects of dabigatran and some of the oral factor Xa inhibitors, respectively, the sensitivity of these tests is variable and reagent dependent. 5Regardless of reagent, the PT is less responsive to apixaban and edoxaban than to rivaroxaban.Unfortunately, because sensitivity to the DO-ACs is rarely considered when reagents are chosen, the utility of the tests may change when laboratories order new lots of reagents.This not only complicates interpretation of test results over time in a single laboratory, but also renders between-laboratory comparisons difficult.These issues highlight the need for standardized tests.The DOACs have half-lives of ≈12 hours.Consequently, circulating drug levels and their subsequent effects on the aPTT and PT depend on when the blood sample was collected relative to the timing of the last drug dose.Even when measured soon after drug intake, a prolonged aPTT in patients taking dabigatran or an elevated PT in those on rivaroxaban, apixaban, or edoxaban gives no information about how much drug is in the circulation, and a normal test result does not exclude the presence of drug.Therefore, more accurate tests are needed.Such tests are currently available in research facilities and include the diluted thrombin time and ecarin clot time or ecarin chromogenic assay for dabigatran, as well as chromogenic anti-factor Xa assays for rivaroxaban, apixaban, and edoxaban. 5Unfortunately, these tests are not widely available, and even if available, the turnaround time is often too slow to be useful.This needs to change.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,025 | 0,061 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,004 | 0,002 |
| Bibliométrie | 0,003 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,004 |
| Communication savante | 0,005 | 0,010 |
| Science ouverte | 0,003 | 0,002 |
| Intégrité de la recherche | 0,008 | 0,013 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,014 | 0,006 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».