Dabigatran, rivaroxaban, apixaban, argatroban and fondaparinux and their effects on coagulation POC and platelet function tests

Thomas Eller; Jessica Busse; Marcus Dittrich; Tobias Flieder; Susanne Alban; Cornelius Knabbe; Ingvild Birschmann

doi:10.1515/cclm-2013-0936

Article

Dabigatran, rivaroxaban, apixaban, argatroban and fondaparinux and their effects on coagulation POC and platelet function tests

Thomas Eller , Jessica Busse , Marcus Dittrich , Tobias Flieder , Susanne Alban , Cornelius Knabbe and Ingvild Birschmann

Published/Copyright: January 9, 2014

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From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 52 Issue 6

Abstract

Background: In recent years, several selectively acting anticoagulants, including the direct thrombin inhibitors (DTI; argatroban, dabigatran) and the factor Xa inhibitors (rivaroxaban, apixaban, fondaparinux), have been developed. With their clinical application increasing, it is of interest to evaluate their interference with classical haemostaseological point-of-care tests. Additionally, the effect of the investigated anticoagulants on platelet function tests will come increasingly more into focus for monitoring not only hereditary platelet dysfunction, but also antiplatelet therapy.

Methods: Blood samples from healthy volunteers were spiked with therapeutic and supratherapeutic concentrations of the drugs listed above and investigated with regard to their effects on the following POCTs: activated clotting time (ACT), thromboelastometry with ROTEM^®, PFA^® and Multiplate^®. Light-transmission aggregometry (LTA) was used for a platelet function assay.

Results: At supratherapeutic concentrations, ACT and ROTEM^® analysis were always influenced after administration of the drugs listed above (except fondaparinux in EXTEM-CT). Therapeutic concentrations showed differential effects on these assays. LTA measurements revealed a distinct decrease in α-thrombin-induced platelet aggregation for both DTIs (therapeutic and supratherapeutic concentrations), while argatroban reduced platelet function in supratherapeutic concentrations. None of the drugs seemed to have any influence on PFA^® or Multiplate^®.

Conclusions: Selective thrombin and factor Xa inhibitors exhibit distinct effects on POCTs and platelet function tests. This must be considered in assessing assay results when taking medical decisions.

Keywords: direct oral anticoagulants; direct thrombin inhibitors; platelets; point-of-care systems; preanalytics

Corresponding author: Ingvild Birschmann, MD, PhD, Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Ruhr University Bochum, Georgstrasse 11, 32545 Bad Oeynhausen, Germany, Phone: +49 5731 97-3819, Fax: +49 5731 97-2307, E-mail: IBirschmann@hdz-nrw.de

aThomas Eller and Jessica Busse contributed equally to this work.

Acknowledgments

The authors wish to thank Andrea Hohbein and Tatjana Gripp for their technical assistance, and Prof. Dr. Michael Fantini for the loan of the ROTEM analyser during this study.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in thestudy design; in the collection, analysis, and interpretationof data; in the writing of the report; or in the decision tosubmit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

T.E. has acted as paid speaker in the past for Siemens Healthcare Diagnostics Products GmbH, Bayer Vital GmbH, Sanofi-Aventis Deutschland GmbH, Pfizer Pharma GmbH, CSL Behring GmbH and Roche Diagnostics Deutschland GmbH and had travel expenses reimbursed by Octapharma GmbH, Novo Nordisk Health Care AG, Baxter Deutschland GmbH, Pfizer Pharma GmbH, Sanofi-Aventis Deutschland GmbH and CSL Behring GmbH. T.F. has had travel expenses paid by Octapharma GmbH, Novo Nordisk Health Care AG, Baxter Deutschland GmbH and Siemens Healthcare Diagnostics Products GmbH. S.A. has acted as paid speaker and been a member of the Advisory Board Bayer Vital GmbH and Bristol-Myers Squibb GmbH & Co. KGaA and Boehringer Ingelheim Pharma GmbH & Co. KG. I.B. has acted as paid speaker in the past for Siemens Healthcare Diagnostics Products GmbH, Bristol-Myers Squibb GmbH & Co. KGaA and Instrumentation Laboratory GmbH, has received research funding from Siemens Healthcare Diagnostics Products GmbH, Baxter Deutschland GmbH, Novo Nordisk Health Care AG and CSL Behring GmbH and travel expenses from Octapharma GmbH, Novo Nordisk Health Care AG, Baxter Deutschland GmbH, Pfizer Pharma GmbH, Sanofi-Aventis Deutschland GmbH and CSL Behring GmbH. J.B., M.D. and C.K. state that they have no conflicts of interest.

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Received: 2013-10-30

Accepted: 2013-12-5

Published Online: 2014-1-9

Published in Print: 2014-6-1

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https://doi.org/10.1515/cclm-2013-0936

Keywords for this article

direct oral anticoagulants; direct thrombin inhibitors; platelets; point-of-care systems; preanalytics

Dabigatran, rivaroxaban, apixaban, argatroban and fondaparinux and their effects on coagulation POC and platelet function tests

Article

Abstract

Acknowledgments

Conflict of interest statement

References

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