Non-Specific Hemostatic Agents (PCC, aPCC, rVIIa) for Reversal of Direct Oral Anticoagulant Effect in Patients with Major Bleeding Complications: A Retrospective Review
Notice bibliographique
Résumé
Abstract Direct oral anticoagulants (DOACs) are used for the prevention and treatment of thromboembolism in a variety of clinical settings. Although rates of DOAC-associated major bleeding are similar to, or lower than that of warfarin, there are currently no antidotes available to reverse DOAC anticoagulant effect. In the absence of specific reversal agents a variety of strategies have evolved to overcome DOAC-induced coagulation inhibition. Widely used agents to treat bleeding in DOAC treated patients include prothrombin complex concentrate (PCC), activated PCC (aPCC, FEIBA) or recombinant activated factor VII (rVIIa); these agents are used despite a known risk of thrombosis and a lack of evidence of efficacy. We present preliminary results of a retrospective review of patients treated with PCC, aPCC and/or rVIIa for DOAC-associated major bleeding at Hamilton Health Sciences, Hamilton, Ontario, Canada to (i) characterize utilization of these agents and (ii) describe the clinical course and complications after administration in this setting. Eligible patients were adults (≥ 18 yrs) treated with PCC, aPCC and/or rVIIa for major DOAC-associated bleeding between 2010 and 2013. After screening 503 patients with anticoagulant associated major bleeding (661 cases), 11 patients (12 cases) were eligible for inclusion with the remainder excluded as they were treated with warfarin. Median age was 81 years (interquartile range [IQR] 74-86) with 64% male. Patients were treated with dabigatran (73%) or rivaroxaban (27%). The majority of patients were treated for atrial fibrillation (91%) with a median CHADS2 score of 3 (IQR 2-3). Bleeding events occurred within 12 hours of DOAC administration in 9 patients (82%) or 13-24 hours in 2 patients (18%). Intracranial hemorrhage was the most common site of bleeding (54%) followed by gastrointestinal (27%), ocular (9%) and body cavity (9%). APCC and PCC were administered to 6 patients (54%) and 5 patients (46%), respectively. Six patients (54%) were admitted to the intensive care unit with median length of stay 2.5 days (IQR 2-4). Three patients (27%) underwent surgical procedures. Median length of hospital admission for the cohort was 10 days (IQR 4-29). There were no thromboembolic complications. In-hospital mortality was 18%. This case series demonstrates that PCC and aPCC are used "off-label" for reversal of DOAC anticoagulant effect in the setting of major bleeding. Our observed mortality rate was generally higher than that reported in the clinical trials leading to DOAC approval; this is likely explained by the severity of bleeding complications of which the majority were intracranial hemorrhage. Our failure to observe thromboembolic complications is reassuring; however, the small sample size does not allow us to confidently rule out even high frequency toxic events. Our results confirm the need for rigorous studies comparing strategies for DOAC reversal in patients with major or life-threatening bleeding. Disclosures Siegal: Daiichi Sankyo: Other: participated in an advisory board; Boerhinger Ingelheim: Other: participated in an advisory board; Portola Pharmaceuticals: Other: participated in an advisory board; Interactive Forums Inc.: Other: created educational slides. Off Label Use: We conducted a chart review of the off-label use of prothrombin complex concentrate, activated prothrombin complex concentrate and recombinant factor VIIa for direct oral anticoagulant reversal..
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 | 0,001 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,004 | 0,007 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
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 ».