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Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays.

Abstract：

:Dabigatran is an oral, reversible thrombin inhibitor that has shown promising results in large clinical trials. Laboratory monitoring is not needed but the effects on common coagulation assays are incompletely known. Dabigatran was added to plasma from healthy subjects in the concentration range 0-1,000 μg/l and analysed using several reagents for activated thromboplastin time (APTT), prothrombin time (PT), fibrinogen, antithrombin, and activated protein C resistance. Typical trough concentrations are about 50 μg/l, peak concentrations 100-300 μg/l. At 100 μg/l all APTT-results were prolonged. The concentration required to double APTT ranged between 227 and 286 μg/l, the responses for all five reagents were similar. PT-reagents were much less affected with almost no samples above INR 1.2 at 100 μg/l. The effect was sample dilution dependent with PT Quick type more sensitive than PT Owren type methods. If a patient on dabigatran has prolonged APTT, >90 seconds, and Quick PT INR>2 or Owren PT INR>1.5 over-dosing or accumulation of dabigatran should be considered. Two of four fibrinogen reagents underestimated the fibrinogen concentration considerably at expected peak concentration. Methods based on inhibition of thrombin over-estimated the antithrombin concentration, but not Xa-based. The APC-resistance methods over-estimated the APC-ratio, which may lead to miss-classification of factor V Leiden patients as being normal. Different coagulation assays, and even different reagents within an assay group, display variable effects at therapeutic concentrations of dabigatran. Some of these assay variations are of clinical importance, thus knowledge is needed for a correct interpretation of results.

journal_name

Thromb Haemost

journal_title

Thrombosis and haemostasis

authors

Lindahl TL,Baghaei F,Blixter IF,Gustafsson KM,Stigendal L,Sten-Linder M,Strandberg K,Hillarp A,Expert Group on Coagulation of the External Quality Assurance in Laboratory Medicine in Sweden.

doi

10.1160/TH10-06-0342

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

371-8

issue

eissn

0340-6245

issn

2567-689X

pii

10-06-0342

journal_volume

105

pub_type

杂志文章

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Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays.