Do Novel Anticoagulants Affect the PT/INR?

Jenny A. Van Amburgh, PharmD, CDE

Disclosures

January 28, 2013

Question

Does rivaroxaban or dabigatran affect the PT or INR? Can either be monitored using the PT or INR?

Response from Jenny A. Van Amburgh, PharmD, CDE
Assistant Dean of Academic Affairs and Associate Clinical Professor, School of Pharmacy, Northeastern University; Director of the Clinical Pharmacy Team and Residency Program Director, Harbor Health Services, Inc., Boston, Massachusetts

Warfarin is the most commonly used anticoagulant for the prevention of thrombosis or stroke. Because of a narrow therapeutic window, it requires regular coagulation monitoring of the prothrombin time (PT)/international normalized ratio (INR).[1] As such, the inconvenience of frequent blood draws remains a major burden. For the first time in over 50 years, 2 new oral anticoagulants, dabigatran, a direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor, were approved by the US Food and Drug Administration. While these anticoagulants carry similar side effects to warfarin, such as risk for gastrointestinal bleeding and intracranial hemorrhage, INR and PT monitoring are not required. How then are providers to gauge the safety and efficacy of the medication in a patient? Can clinicians monitor these medications with the conventional coagulation assays, or are they rendered useless?[1]

The effect of both dabigatran and rivaroxaban on commonly used coagulation assays has been evaluated in the literature, both in vitro and in vivo. The usefulness of these tests relates directly to the medications' mechanisms of action. For both agents, the use of an INR to determine the effectiveness and safety is meaningless because INR is calibrated for use with vitamin K antagonists (such as warfarin) only.[1] Although use may be associated with an increase in INR, this increase does not relate to the effectiveness of therapy or provide a linear correlation of concentration and effect that is seen when measuring warfarin levels.[2,3] In some instances, point-of-care INR measurements have been drawn on patients using dabigatran; however, the results have failed to correlate to appropriateness in therapy and have varied greatly case by case.[4]

As dabigatran directly inhibits thrombin, PT measures lack the sensitivity to detect therapeutic levels.[1,5] Often, if this assay is measured in patients taking dabigatran, a subtherapeutic level is noted, regardless of concentration of dabigatran.[6] More appropriate assays for dabigatran may be activated partial thromboplastin time (aPTT), diluted thrombin time (TT), or ecarin clotting time (ECT). These tests are better able to capture changes throughout the clotting cascade. Using aPTT may underestimate high levels and could be used more as a qualitative assessment of activity instead of a quantitative assessment.[7] Where available and if desired, monitoring via the diluted TT or ECT has proved a more useful measure for dabigatran.[1]

Unlike dabigatran, studies have demonstrated a correlation between the levels of rivaroxaban and PT through inhibition of factor Xa, but not to the same extent as warfarin.[8] In some instances, the use of PT monitoring for this medication may be useful. A linear response between PT and rivaroxaban can be seen; however, the accuracy of the test improves when concentrations of rivaroxaban are higher. Additionally, the use of PT for monitoring rivaroxaban can be difficult because the measurement differs greatly depending on the reagent used to determine PT. Calibrating PT assays to assess rivaroxaban appropriately is an option currently being evaluated.[8]

In conclusion, the INR is not a viable option when assessing the use of dabigatran or rivaroxaban. Additionally, PT is not a viable option when monitoring a patient on dabigatran. However, PT may be an option for monitoring select patients on rivaroxaban until more reliable standardized tests are developed. Methods of measuring the effectiveness of these agents are currently being developed and tested; however, until they are made available, the existing tests may be adapted to be used in a more effective manner.

The author wishes to acknowledge the assistance of Jacqueline M. Kraft, PharmD, Ngoc Diem Nguyen, PharmD, and Phillipa Scheele, PharmD, PGY1 Residents, and Michael P. Conley, PharmD, and Nga T. Pham, PharmD, CDE, AE-C, Assistant Clinical Professors at Northeastern University -- School of Pharmacy and Harbor Health Services, Inc., Boston, Massachusetts.

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