Direct Oral Anticoagulants Form Thrombus Different From Warfarin in a Microchip Flow Chamber System

Abstract Direct oral anticoagulants (DOACs) have low risk of intracranial hemorrhage compared to warfarin. We sought to clarify the different mechanisms responsible for suppression of bleeding events using the Total Thrombus-formation Analysis System (T-TAS), a flow-microchip chamber with thrombogen...

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Autores principales: Masanobu Ishii, Koichi Kaikita, Miwa Ito, Daisuke Sueta, Yuichiro Arima, Seiji Takashio, Yasuhiro Izumiya, Eiichiro Yamamoto, Megumi Yamamuro, Sunao Kojima, Seiji Hokimoto, Hiroshige Yamabe, Hisao Ogawa, Kenichi Tsujita
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:a051c3d32ddf4095a83804444ee2443f2021-12-02T15:06:27ZDirect Oral Anticoagulants Form Thrombus Different From Warfarin in a Microchip Flow Chamber System10.1038/s41598-017-07939-62045-2322https://doaj.org/article/a051c3d32ddf4095a83804444ee2443f2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07939-6https://doaj.org/toc/2045-2322Abstract Direct oral anticoagulants (DOACs) have low risk of intracranial hemorrhage compared to warfarin. We sought to clarify the different mechanisms responsible for suppression of bleeding events using the Total Thrombus-formation Analysis System (T-TAS), a flow-microchip chamber with thrombogenic surfaces. Blood samples were obtained at Off- and On-anticoagulant (trough) from 120 consecutive patients with atrial fibrillation (warfarin; n = 29, dabigatran; n = 19, rivaroxaban; n = 47, apixaban; n = 25), which were used for T-TAS to compute the area under the curve (AUC) (AR10-AUC30) in the AR chip, and to measure plasma concentrations of DOACs at On-anticoagulant. In addition, the two-dimensional area covered by thrombi (%) in the capillary was analyzed every 3 minutes after sample applications. The AR10-AUC30 correlated weakly and negatively with plasma concentrations of DOACs, and the levels at On-anticoagulant were lower in all groups than at Off-anticoagulant. AR10-AUC30 levels at Off- and On-anticoagulant were identical among the groups. The thrombi areas in early phase were significantly larger in rivaroxaban and apixaban than warfarin and dabigatran groups. The findings suggested that visual analysis of the AR-chip can identify the differential inhibitory patterns of warfarin and DOACs on thrombus formation under flow condition.Masanobu IshiiKoichi KaikitaMiwa ItoDaisuke SuetaYuichiro ArimaSeiji TakashioYasuhiro IzumiyaEiichiro YamamotoMegumi YamamuroSunao KojimaSeiji HokimotoHiroshige YamabeHisao OgawaKenichi TsujitaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Masanobu Ishii
Koichi Kaikita
Miwa Ito
Daisuke Sueta
Yuichiro Arima
Seiji Takashio
Yasuhiro Izumiya
Eiichiro Yamamoto
Megumi Yamamuro
Sunao Kojima
Seiji Hokimoto
Hiroshige Yamabe
Hisao Ogawa
Kenichi Tsujita
Direct Oral Anticoagulants Form Thrombus Different From Warfarin in a Microchip Flow Chamber System
description Abstract Direct oral anticoagulants (DOACs) have low risk of intracranial hemorrhage compared to warfarin. We sought to clarify the different mechanisms responsible for suppression of bleeding events using the Total Thrombus-formation Analysis System (T-TAS), a flow-microchip chamber with thrombogenic surfaces. Blood samples were obtained at Off- and On-anticoagulant (trough) from 120 consecutive patients with atrial fibrillation (warfarin; n = 29, dabigatran; n = 19, rivaroxaban; n = 47, apixaban; n = 25), which were used for T-TAS to compute the area under the curve (AUC) (AR10-AUC30) in the AR chip, and to measure plasma concentrations of DOACs at On-anticoagulant. In addition, the two-dimensional area covered by thrombi (%) in the capillary was analyzed every 3 minutes after sample applications. The AR10-AUC30 correlated weakly and negatively with plasma concentrations of DOACs, and the levels at On-anticoagulant were lower in all groups than at Off-anticoagulant. AR10-AUC30 levels at Off- and On-anticoagulant were identical among the groups. The thrombi areas in early phase were significantly larger in rivaroxaban and apixaban than warfarin and dabigatran groups. The findings suggested that visual analysis of the AR-chip can identify the differential inhibitory patterns of warfarin and DOACs on thrombus formation under flow condition.
format article
author Masanobu Ishii
Koichi Kaikita
Miwa Ito
Daisuke Sueta
Yuichiro Arima
Seiji Takashio
Yasuhiro Izumiya
Eiichiro Yamamoto
Megumi Yamamuro
Sunao Kojima
Seiji Hokimoto
Hiroshige Yamabe
Hisao Ogawa
Kenichi Tsujita
author_facet Masanobu Ishii
Koichi Kaikita
Miwa Ito
Daisuke Sueta
Yuichiro Arima
Seiji Takashio
Yasuhiro Izumiya
Eiichiro Yamamoto
Megumi Yamamuro
Sunao Kojima
Seiji Hokimoto
Hiroshige Yamabe
Hisao Ogawa
Kenichi Tsujita
author_sort Masanobu Ishii
title Direct Oral Anticoagulants Form Thrombus Different From Warfarin in a Microchip Flow Chamber System
title_short Direct Oral Anticoagulants Form Thrombus Different From Warfarin in a Microchip Flow Chamber System
title_full Direct Oral Anticoagulants Form Thrombus Different From Warfarin in a Microchip Flow Chamber System
title_fullStr Direct Oral Anticoagulants Form Thrombus Different From Warfarin in a Microchip Flow Chamber System
title_full_unstemmed Direct Oral Anticoagulants Form Thrombus Different From Warfarin in a Microchip Flow Chamber System
title_sort direct oral anticoagulants form thrombus different from warfarin in a microchip flow chamber system
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/a051c3d32ddf4095a83804444ee2443f
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