Abstract：
OBJECTIVES:Dabigatran etexilate is widely used for stroke prevention in the patients with atrial fibrillation. The anticoagulation activity of dabigatran is not necessary monitored in routine clinical practice. We aimed to study the effect of dabigatran on thrombin generation (TG) and coagulation assays in rabbit and human plasma. METHODS:Rabbits received different concentrations of dabigatran etexilate (5 mg/kg, 10 mg/kg). Patients with atrial fibrillation took 110 mg dabigatran etexilate twice daily. The concentrations of dabigatran in rabbit and human plasma were detected by liquid chromatography/tandem mass spectrometry (LC-MS/MS) and ecarin chromogenic assay (ECA). The relationship between plasma dabigatran concentrations and the activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), and TG were evaluated. RESULTS:There was strong correlation between LC-MS/MS and ECA (P < 0.001). Bland Altman analysis demonstrated that ECA assay could accurately predict human plasma dabigatran concentrations whereas underestimate the plasma concentrations of dabigatran in rabbits. Both the PT and the aPTT assays showed low correlations with dabigatran. The TT assay was highly sensitive to dabigatran levels. Low concentrations of dabigatran paradoxically increased TG. CONCLUSIONS:LC-MS/MS is the gold standard for detecting the concentrations of dabigatran. ECA correlates well with LC-MS/MS. The coagulation assays depend more on other factors. Paradoxical enhancement of TG may predict clinically rebound hypercoagulability and warrants further exploration.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Zhang C,Zhang P,Li H,Han L,Zhang L,Zhang L,Yang Xdoi
10.1016/j.thromres.2018.03.012subject
Has Abstractpub_date
2018-05-01 00:00:00pages
38-43eissn
0049-3848issn
1879-2472pii
S0049-3848(18)30289-5journal_volume
165pub_type
杂志文章abstract：INTRODUCTION:The outstanding importance of (soluble) CD40L to cardiovascular disease (CVD) is becoming increasingly apparent as CD40L is an important mediator of thrombotic and inflammatory processes. Platelets are the main source for CD40 ligand, linking platelet stimulatory events to inflammation and adverse adaptive...
journal_title：Thrombosis research
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journal_title：Thrombosis research
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doi：10.1016/0049-3848(96)00004-7
更新日期：1996-02-01 00:00:00
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pub_type： 杂志文章
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journal_title：Thrombosis research
pub_type： 杂志文章,随机对照试验
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pub_type： 杂志文章
doi：10.1016/s0049-3848(97)00162-x
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pub_type： 杂志文章
doi：10.1016/j.thromres.2015.01.025
更新日期：2015-05-01 00:00:00
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(85)90207-5
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更新日期：2019-08-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0049-3848(85)90123-9
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pub_type： 杂志文章
doi：10.1016/j.thromres.2019.10.019
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pub_type： 杂志文章
doi：10.1016/0049-3848(84)90211-1
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pub_type： 杂志文章,评审
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pub_type： 杂志文章,评审
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更新日期：2019-07-01 00:00:00
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pub_type： 杂志文章,随机对照试验
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更新日期：2013-09-01 00:00:00
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pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期：2008-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/0049-3848(93)90043-n
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/0049-3848(82)90210-9
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journal_title：Thrombosis research
pub_type： 杂志文章
doi：10.1016/j.thromres.2015.01.027
更新日期：2015-04-01 00:00:00
