Overview and Practical Application of Coagulation Assays in Managing Anticoagulation with Direct Oral Anticoagulants (DOACs)

Abstract

Purpose of Review

The introduction of newer anticoagulants requires clinicians to fully appreciate, interpret, and correctly apply the use of coagulation assays, such as the prothrombin time (PT), activated partial thromboplastin time (APTT), and anti-factor Xa assays. For oral vitamin K antagonists, the international normalized ratio (INR) is a predictor of anticoagulation intensity. However, for direct oral anticoagulants (DOACs), the PT or INR and APTT are unable to quantify the level of anticoagulation intensity as there is a poor correlation between plasma concentration of DOAC with these routine coagulation assays and that significant anticoagulant effect may still be present despite normal or near normal results for these routine assays.

Recent Findings

In the USA, there are 5 DOACs available including dabigatran, a direct thrombin inhibitor and 4 direct factor Xa inhibitors (FXaI), each with varying indications, doses, pharmacodynamic, and pharmacokinetic characteristics. A thorough understanding of these properties aids in the management of the periprocedural or bleeding patient.

Summary

In this first section of this manuscript, we will review the laboratory tests that are commonly performed for assessing a patient’s coagulation status with known DOAC exposure. The second section will describe 3 real-world challenging case studies in DOAC-treated patients, with a focus on presenting clinical queries, interpretation of baseline laboratory tests with interpretations, followed by the case discussion to combine interpretation of appropriate laboratory tests with clinical patient considerations in an effort to guide clinical decision-making.

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Correspondence to Robert C Gosselin.

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Conflict of Interest

Mr. Gosselin reports personal fees from Expert testimony for rivaroxaban and dabigatran testing, other from Diagnostica Stago, personal fees from Diagnostica Grifols, personal fees from UniQure, other from BioMarin, personal fees from Machaon Diagnostic Laboratory, other from Siemens Healthcare Diagnostics, outside the submitted work; Dr. Douxfils reports personal fees from QUALIblood , personal fees from Stago Diagnostica, personal fees from Daiichi Sankyo, personal fees from Roche, personal fees from Roche Diagnostics, personal fees from Portola, outside the submitted work; In addition, Dr. Douxfils has a patent PCT/EP2019/052903 pending.

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Rimsans, J., Douxfils, J., Smythe, M.A. et al. Overview and Practical Application of Coagulation Assays in Managing Anticoagulation with Direct Oral Anticoagulants (DOACs). Curr Pharmacol Rep 6, 241–259 (2020). https://doi.org/10.1007/s40495-020-00232-7

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Keywords

  • Direct oral anticoagulants
  • Laboratory testing
  • Dabigatran
  • Rivaroxaban
  • Apixaban
  • Edoxaban
  • Betrixaban
  • Ecarin
  • Anti-FXa
  • Thrombin generation
  • Andexanet
  • Dilute thrombin time
  • Thrombin time