Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays
(2011) In Thrombosis and Haemostasis 105(2). p.371-378- 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... (More)
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.
(Less)
- author
- Lindahl, Tomas L ; Baghaei, Fariba ; Blixter, Inger Fagerberg ; Gustafsson, Kerstin M ; Stigendal, Lennart ; Strandberg, Karin LU and Hillarp, Andreas LU
- author collaboration
- organization
- publishing date
- 2011-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Activated Protein C Resistance/blood, Administration, Oral, Adult, Aged, Antithrombins/administration & dosage, Benzimidazoles/administration & dosage, Blood Coagulation/drug effects, Blood Coagulation Tests, Dabigatran, Dose-Response Relationship, Drug, Female, Fibrinogen/metabolism, Humans, Male, Middle Aged, Partial Thromboplastin Time, Prothrombin Time, Reproducibility of Results, Thrombin/antagonists & inhibitors, beta-Alanine/administration & dosage
- in
- Thrombosis and Haemostasis
- volume
- 105
- issue
- 2
- pages
- 371 - 378
- publisher
- Schattauer GmbH
- external identifiers
-
- scopus:79851482951
- pmid:21103660
- ISSN
- 0340-6245
- DOI
- 10.1160/TH10-06-0342
- language
- English
- LU publication?
- yes
- id
- 86008858-2ef8-42d0-aba6-abfa587841a5
- date added to LUP
- 2022-08-29 10:16:14
- date last changed
- 2024-06-13 18:28:32
@article{86008858-2ef8-42d0-aba6-abfa587841a5,
abstract = {{<p>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.</p>}},
author = {{Lindahl, Tomas L and Baghaei, Fariba and Blixter, Inger Fagerberg and Gustafsson, Kerstin M and Stigendal, Lennart and Strandberg, Karin and Hillarp, Andreas}},
issn = {{0340-6245}},
keywords = {{Activated Protein C Resistance/blood; Administration, Oral; Adult; Aged; Antithrombins/administration & dosage; Benzimidazoles/administration & dosage; Blood Coagulation/drug effects; Blood Coagulation Tests; Dabigatran; Dose-Response Relationship, Drug; Female; Fibrinogen/metabolism; Humans; Male; Middle Aged; Partial Thromboplastin Time; Prothrombin Time; Reproducibility of Results; Thrombin/antagonists & inhibitors; beta-Alanine/administration & dosage}},
language = {{eng}},
number = {{2}},
pages = {{371--378}},
publisher = {{Schattauer GmbH}},
series = {{Thrombosis and Haemostasis}},
title = {{Effects of the oral, direct thrombin inhibitor dabigatran on five common coagulation assays}},
url = {{http://dx.doi.org/10.1160/TH10-06-0342}},
doi = {{10.1160/TH10-06-0342}},
volume = {{105}},
year = {{2011}},
}