Thrombin generation in real life bleeding patients on oral anticoagulants reversed (or not) with (activated) prothrombin complex concentrate.
4F-PCC
Anticoagulant agent
Bleeding
DOACs
Thrombin generation assay
Journal
Thrombosis research
ISSN: 1879-2472
Titre abrégé: Thromb Res
Pays: United States
ID NLM: 0326377
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
18
10
2022
revised:
18
01
2023
accepted:
21
01
2023
pubmed:
11
2
2023
medline:
4
3
2023
entrez:
10
2
2023
Statut:
ppublish
Résumé
Bleeding during oral anticoagulant therapy is currently codified by expert guidelines. Monitoring of coagulation during bleeding events is challenging. Our study sought to assess thrombin generation assay (TGA) in direct oral anticoagulant-treated patients without bleeding (WB), bleeding without reversal therapy (BR-), and bleeding with reversal therapy (BR+). We conducted a prospective, monocentric study from June 2015 to June 2018. For all bleeding groups, TGA was evaluated using platelet-poor plasma collected upon arrival at emergency (T0), and 30 min (T1), 6 h (T2) and 24 h (T3) after reversal therapy (if indicated) following activation by tissue factor 5 pM and phospholipids. Overall, 292 patients participated, including 91 BR+, 94 BR-, and 107 WB patients. At T0, vitamin K antagonist reversed (VKA-BR+) patients experienced a significant decrease in TGA parameters (ETP and peak) compared with VKA without bleeding (VKA-WB). Compared with healthy controls, VKA-BR+ patients reversed by four-factor prothrombin complex concentrate (4F-PCC) displayed comparable TGA 's ETP and peak at T1, T2, and T3, whereas direct anti-Xa BR+ patients reversed by 4F-PCC or activated prothrombin complex concentrate (aPCC) reached thrombin generation parameters that exceeded normal range at T2 and T3. In VKA-treated patients reversed by 4F-PCC, TGA parameters were normalized, whereas in rivaroxaban or apixaban-treated patients reversed by 4F-PCC or aPCC, TGA parameters exceeded normal range. Further studies are needed to compare the efficacy and safety of a different dose of reversal therapy and the impact on coagulation parameters.
Sections du résumé
BACKGROUND
Bleeding during oral anticoagulant therapy is currently codified by expert guidelines. Monitoring of coagulation during bleeding events is challenging. Our study sought to assess thrombin generation assay (TGA) in direct oral anticoagulant-treated patients without bleeding (WB), bleeding without reversal therapy (BR-), and bleeding with reversal therapy (BR+).
METHODS
We conducted a prospective, monocentric study from June 2015 to June 2018. For all bleeding groups, TGA was evaluated using platelet-poor plasma collected upon arrival at emergency (T0), and 30 min (T1), 6 h (T2) and 24 h (T3) after reversal therapy (if indicated) following activation by tissue factor 5 pM and phospholipids.
RESULTS
Overall, 292 patients participated, including 91 BR+, 94 BR-, and 107 WB patients. At T0, vitamin K antagonist reversed (VKA-BR+) patients experienced a significant decrease in TGA parameters (ETP and peak) compared with VKA without bleeding (VKA-WB). Compared with healthy controls, VKA-BR+ patients reversed by four-factor prothrombin complex concentrate (4F-PCC) displayed comparable TGA 's ETP and peak at T1, T2, and T3, whereas direct anti-Xa BR+ patients reversed by 4F-PCC or activated prothrombin complex concentrate (aPCC) reached thrombin generation parameters that exceeded normal range at T2 and T3.
CONCLUSIONS
In VKA-treated patients reversed by 4F-PCC, TGA parameters were normalized, whereas in rivaroxaban or apixaban-treated patients reversed by 4F-PCC or aPCC, TGA parameters exceeded normal range. Further studies are needed to compare the efficacy and safety of a different dose of reversal therapy and the impact on coagulation parameters.
Identifiants
pubmed: 36764085
pii: S0049-3848(23)00029-4
doi: 10.1016/j.thromres.2023.01.022
pii:
doi:
Substances chimiques
prothrombin complex concentrates
37224-63-8
Thrombin
EC 3.4.21.5
Blood Coagulation Factors
0
Anticoagulants
0
Factor VIIa
EC 3.4.21.21
Factor IX
9001-28-9
Factor VIII
9001-27-8
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
184-193Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest Dr. Moustafa has served as a consultant for Bayer HealthCare Pharmaceuticals and Sanofi, been a speaker for Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Daiichi-Sankyo, Leo-pharma, Pfizer and Sanofi, and has received grants from Sanofi, Bayer HealthCare, and LFB. Dr. Schmidt has received payments for board membership from Bayer, Daichi, Lilly, and Pfizer, as well as personal compensation from Biomerieux, Bohringer Ingelheim, Sanofi, Leo-pharma, and Novartis. Dr. Lebreton has participated in advisory boards for Boehringer Ingelheim and Bayer.