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Anti-coagulation assessment with prothrombin time and anti-Xa assays in real-world patients on treatment with rivaroxaban

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Abstract

Monitoring of anti-coagulation with the direct factor Xa inhibitor rivaroxaban is considered unnecessary in a routine clinical setting. However, assessment of its anti-coagulant effect may be desirable in certain clinical situations. We assessed prothrombin time (PT) reagents and commercially available anti-Xa assays (Biophen) calibrated for rivaroxaban and heparin in comparison to liquid chromatography–mass spectrometry (LC-MS/MS) measurements of rivaroxaban concentration in samples from patients on treatment with rivaroxaban for stroke prevention in atrial fibrillation. Citrate plasma samples were obtained from 30 randomly selected patients on uninterrupted treatment with rivaroxaban for a minimum of 1 month. The anti-Xa assays, direct Xa inhibitor (DiXa-I®), and Heparin LRT® were conducted for both wide and low calibrations for rivaroxaban. Measurements were compared to LC-MS/MS using correlation, linear regression, intra-class correlation, and Bland–Altman analysis. In 30 patients (9 female) of median age 71.5 years and BMI 26.5 kg/m2, rivaroxaban concentrations between 2.4 and 625 ng/ml (median 82 ng/ml) were measured by LC-MS/MS. PT reagents were poorly correlated with rivaroxaban concentrations (r 2 = 0.52 and 0.09). Anti-Xa assays DiXa-I (r 2 = 0.95) and Heparin LRT (r 2 = 0.97) were correlated with rivaroxaban in all concentrations, but especially in low concentrations with low calibrations (r 2 = 0.97 and 0.98, respectively). The highest agreement occurred between Heparin LRT and low rivaroxaban concentrations with a mean difference of −5.3 ng/ml (limits of agreement, 12.9 to 2.4 ng/ml). Anti-Xa assays can indirectly determine the concentration of rivaroxaban for a wide range of concentrations in real-world patients. An interpretation of anti-Xa and PT measurements in treatment with rivaroxaban requires knowledge of the local reagents.

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Acknowledgments

We thank the clinical collaborators Johannes Thaler, Johanna Gebhart (Department of Hematology and Hemostaseology), Giora Meron (Department of Emergency Medicine/Ophthalmology), Martin Frossard (Department of Emergency Medicine/Trauma Surgery), and Christoph Kratochwill (Department of Internal Medicine II, all Medical University of Vienna) for contributing patient samples. The anti-Xa reagents, calibrators, and controls were kindly provided by CoaChrom Diagnostica GmbH, Maria Enzersdorf, Austria.

Funding

This investigation was supported by an unrestricted grant from Daiichi-Sankyo Austria.

Conflict of interest

The authors declare that they have no conflicts of interest.

Authors contribution

OK acquired data, analyzed and interpreted data, drafted the manuscript, and approved the final version for publication.

SB acquired data, analyzed and interpreted data, critically revised the manuscript for important intellectual content, and approved the final version for publication.

PQ analyzed and interpreted data, critically revised the manuscript for important intellectual content, and approved the final version for publication.

CS designed and validated the LC-MS/MS platform, acquired data, critically revised the manuscript for important intellectual content, and approved the final version for publication.

GW acquired data, critically revised the manuscript for important intellectual content and approved the final version for publication.

AG acquired data, critically revised the manuscript for important intellectual content, and approved the final version for publication.

IP designed and conceived the study interpreted data, critically revised the manuscript for important intellectual content, and approved the final version for publication.

CA designed and conceived the study, analyzed and interpreted data, critically revised the manuscript for important intellectual content and, approved the final version for publication.

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Authors and Affiliations

  1. Clinical Division of Hematology and Hemostaseology, Department of Internal Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria

    Oliver Königsbrügge, Ingrid Pabinger & Cihan Ay

  2. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria

    Peter Quehenberger & Sabine Belik

  3. Central Institute for Medical and Chemical Laboratory Diagnostics, Innsbruck Medical University, Innsbruck, Austria

    Günter Weigel, Christoph Seger & Andrea Griesmacher

Authors
  1. Oliver Königsbrügge
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  2. Peter Quehenberger
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  3. Sabine Belik
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  4. Günter Weigel
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  5. Christoph Seger
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  6. Andrea Griesmacher
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  7. Ingrid Pabinger
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  8. Cihan Ay
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Correspondence to Cihan Ay.

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Königsbrügge, O., Quehenberger, P., Belik, S. et al. Anti-coagulation assessment with prothrombin time and anti-Xa assays in real-world patients on treatment with rivaroxaban. Ann Hematol 94, 1463–1471 (2015). https://doi.org/10.1007/s00277-015-2407-y

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  • DOI: https://doi.org/10.1007/s00277-015-2407-y

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