The addition of idarucizumab to plasma samples containing dabigatran allows the use of routine coagulation assays for the diagnosis of hemostasis disorders.
BACKGROUND
The anticoagulant effect of dabigatran can be approximated by its prolongation of routine coagulation assays. Consequently, dabigatran also interferes with thrombophilia screening or with diagnosing hemostasis disorders that have developed after the initiation of anticoagulant treatment, such as vitamin K deficiency or acquired hemophilia A.


OBJECTIVE
This study was carried out to determine whether idarucizumab, a humanized antibody fragment that binds dabigatran, could fully neutralize dabigatran in routine diagnostic coagulation assays conducted in vitro, thereby preventing false-positive or false-negative diagnostic readouts.


METHODS
Preliminary experiments identified coagulation assays that were sensitive to dabigatran, and identified a concentration of idarucizumab that neutralized the effects of dabigatran. These assays were then carried out with patient and control plasma samples spiked with dabigatran, with or without a molar excess of idarucizumab.


RESULTS
Dabigatran altered the prothrombin time, activated partial thromboplastin time and thrombin time, and the measurement of intrinsic and extrinsic factor levels. Screening and confirmation tests used for lupus anticoagulant detection were prolonged by dabigatran, falsely suggesting the presence of lupus anticoagulant. Conversely, the addition of dabigatran falsely corrected an abnormal activated protein C resistance ratio. Addition of idarucizumab completely normalized these measurements, and allowed the correct identification of normal and abnormal samples with these assays.


CONCLUSIONS
In vitro addition of idarucizumab to plasma samples containing dabigatran fully neutralizes the drug, and facilitates the use of routine coagulation assays to allow the diagnosis of hemostasis disorders that may be concurrently present in patients taking dabigatran.
Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.|Clinical Department of Laboratory Medicine, University Hospitals of Leuven, Leuven, Belgium.
M
M
Jacquemin
Clinical Department of Laboratory Medicine, University Hospitals of Leuven, Leuven, Belgium.
J
J
Toelen
Clinical Department of Laboratory Medicine, University Hospitals of Leuven, Leuven, Belgium.
J
J
Schoeters
Clinical Department of Laboratory Medicine, University Hospitals of Leuven, Leuven, Belgium.
I
I
van Horenbeeck
Clinical Department of Laboratory Medicine, University Hospitals of Leuven, Leuven, Belgium.
I
I
Vanlinthout
Clinical Department of Laboratory Medicine, University Hospitals of Leuven, Leuven, Belgium.
M
M
Debasse
Clinical Department of Laboratory Medicine, University Hospitals of Leuven, Leuven, Belgium.
M
M
Peetermans
Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.|Vascular Medicine and Hemostasis, University Hospitals of Leuven, Leuven, Belgium.
T
T
Vanassche
Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.|Vascular Medicine and Hemostasis, University Hospitals of Leuven, Leuven, Belgium.
K
K
Peerlinck
Department of CardioMetabolic Disease Research, Boehringer Ingelheim Pharma GmbH & Co KG, Biberach, Germany.
J
J
van Ryn
Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.|Vascular Medicine and Hemostasis, University Hospitals of Leuven, Leuven, Belgium.
P
P
Verhamme
D020016:Activated Protein C Resistance / Q000097:blood; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity; D000991:Antithrombins / Q000097:blood* / Q000276:immunology / Q000494:pharmacology; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000188:drug therapy; D001780:Blood Coagulation Tests; D000069604:Dabigatran / Q000037:antagonists & inhibitors / Q000097:blood* / Q000276:immunology / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005188:False Negative Reactions; D005189:False Positive Reactions; D006467:Hemophilia A / Q000097:blood; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000097:blood
D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000991:Antithrombins; D016682:Lupus Coagulation Inhibitor; C000594745:idarucizumab; D000069604:Dabigatran
dabigatran; hemophilia A; idarucizumab; lupus anticoagulant; thrombophilia