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. 2017 Oct;15(6):562-567.
doi: 10.2450/2017.0199-16. Epub 2017 Mar 7.

Effect of dabigatran on a prothrombinase-based assay for detecting activated protein C resistance: an ex vivo and in vitro study in normal subjects and factor V Leiden carriers

Gianluca Gessoni  1 , Sara Valverde  2 , Letizia Valle  3 , Pierpaolo Caruso  4 , Francesca Gessoni  2 , Roberto Valle  3
Affiliations

Effect of dabigatran on a prothrombinase-based assay for detecting activated protein C resistance: an ex vivo and in vitro study in normal subjects and factor V Leiden carriers

Gianluca Gessoni et al. Blood Transfus. 2017 Oct.

Abstract

Background: The aim of this study was to evaluate ex vivo and in vitro interference of a direct factor IIa inhibitor, dabigatran, on a prothrombinase-based assay to detect activated protein C resistance.

Materials and methods: An ex vivo study was performed in six heterozygous factor V Leiden carriers and 12 normal subjects without the factor V Leiden mutation who were treated with dabigatran. An in vitro study was also performed considering 12 plasma samples (six from normal subjects and six from heterozygous factor V Leiden carriers) spiked with dabigatran. The dabigatran concentration was evaluated using a diluted thrombin time assay, activated protein C resistance was evaluated using a prothrombinase-based assay.

Results: In both the ex vivo and in vitro studies dabigatran interfered significantly with activated protein C resistance ratios observed in normal subjects and in factor V Leiden heterozygous carriers.

Discussion: The results reported in this paper seem to confirm that dabigatran is able to interfere with the Penthafarm prothrombinase-based assay used to study activated protein C resistance, significantly increasing observed ratios. This effect appears to be present already at low concentrations of dabigatran (6 ng/mL) and affects both normal subjects and heterozygous carriers of factor V Leiden. In this group of patients, dabigatran, at concentrations in the therapeutic range (100-200 ng/mL), could markedly increase the activated protein C resistance ratio, bringing it up to within the reference range for normal subjects, thus potentially leading to misclassification of patients.

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Conflict of interest statement

Disclousure of conflicts of interest

GG, SV, LV, FG and RV are employers of Italian National Health Service. PC is an employee of DASIT SpA.

Figures

Figure 1
Figure 1
Activated protein C resistance (APCr) ratios and dabigatran etexilate (DAB) concentrations in (A) FV wild-type subjects and (B) FV Leiden heterozygous patients: ex vivo results.
Figure 2
Figure 2
Activated protein C resistance (APCr) ratios and dabigatran etexilate (DAB) concentrations in (A) FV wild-type subjects and (B) FV Leiden heterozygous patients: in vitro results.
See this image and copyright information in PMC

Comment in

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