Abstract:
INTRODUCTION:Patients with intracerebral hemorrhage during rivaroxaban treatment have small hematoma and favorable outcomes compared with those with warfarin. We investigated its possible mechanism, focusing on prothrombin fragment 1+2 (F1+2), a marker of thrombin generation. MATERIALS AND METHODS:In 65 patients with acute cardioembolic stroke (median 77years), rivaroxaban was initiated at 5days after the onset. Plasma F1+2 level (normal range, 69-229pmol/L), prothrombin time (PT), and rivaroxaban concentration evaluated by anti-Xa activity were serially measured. RESULTS:Median plasma F1+2 was 276 (IQR, 195-454) pmol/L before starting rivaroxaban, and significantly decreased to 196 (141-267) and 192 (151-248) on 7 and 28days after rivaroxaban, respectively (both p<0.05). Serial measurements of PT and rivaroxaban concentration at trough, 2, 4, and 6h after taking rivaroxaban showed a positive correlation (R2=0.69, p<0.01). PT at 4h after rivaroxaban was significantly prolonged compared with trough (16.6 versus 11.5s, p<0.0001). F1+2 at 4h was also decreased compared with trough (160 (123-245.5) versus 196 (141-266.5), p=0.04), but no patients showed F1+2 below the normal range at 4h. In other 34 patients with warfarin treatment (77years), median PT-INR and F1+2 were 2.06 (1.75-2.50) and 75 (48-111) (p<0.0001 versus 4h after rivaroxaban). Notably, of those with PT-INR≥2.0 (18/34), 12 (12/18, 67%) showed F1+2 below the normal range. CONCLUSIONS:Rivaroxaban retains a normal thrombin generation even at its peak level with prolonged PT, whereas warfarin at therapeutic levels inhibits thrombin generation. This may partly explain different outcomes in patients complicated with bleeding events.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Hagii J,Tomita H,Metoki N,Tamai Y,Saito S,Shiroto H,Hitomi H,Kamada T,Seino S,Takahashi K,Sasaki S,Yasujima M,Okumura Kdoi
10.1016/j.thromres.2016.10.011subject
Has Abstractpub_date
2016-12-01 00:00:00pages
9-14eissn
0049-3848issn
1879-2472pii
S0049-3848(16)30584-9journal_volume
148pub_type
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doi:10.1016/0049-3848(95)00207-3
更新日期:1995-12-15 00:00:00
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doi:10.1016/0049-3848(87)90405-1
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journal_title:Thrombosis research
pub_type: 杂志文章,评审
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(93)90188-t
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journal_title:Thrombosis research
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doi:10.1016/0049-3848(85)90325-1
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更新日期:2015-12-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(93)90029-n
更新日期:1993-02-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/s0049-3848(99)00040-7
更新日期:1999-09-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(98)00160-1
更新日期:1998-12-15 00:00:00
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pub_type: 杂志文章,meta分析
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更新日期:2010-06-01 00:00:00
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journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.thromres.2012.07.014
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pub_type: 杂志文章
doi:10.1016/0049-3848(90)90399-w
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pub_type: 杂志文章,评审
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更新日期:2010-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:1986-01-15 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章,评审
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更新日期:2012-03-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
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更新日期:1987-12-15 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.05.011
更新日期:2010-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2020-07-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(93)90079-4
更新日期:1993-06-01 00:00:00
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journal_title:Thrombosis research
pub_type: 临床试验,杂志文章
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更新日期:1996-11-01 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90300-9
更新日期:1989-09-15 00:00:00
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journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.06.014
更新日期:2013-08-01 00:00:00