Evaluation of the Effect of Apixaban on INR in the Inpatient Population

Abstract

Direct oral anticoagulants (DOACs), particularly direct factor Xa inhibitors, have been associated with prolongation of the prothrombin time and the international normalized ratio (INR). Although DOACs do not require monitoring, elevations in the INR have been reported in in vitro and observational studies. The literature surrounding the extent of elevation and the clinical significance is limited. The objective of this study was to quantify the degree of INR elevation in hospitalized patients receiving apixaban. This was a single-center, retrospective, observational analysis of adult patients who received at least 1 dose of apixaban during their hospital admission and had at least 1 INR sample collected prior to and following administration. The major end point of this study was to characterize the effect of apixaban on the INR by determining the percentage of patients with an INR higher than our laboratory defined normal (defined as INR > 1.1). Minor end point outcomes included the incidence of an INR increase >0.3 from baseline INR and additional patient-specific factors that may influence INR elevation. Seventy-nine patients were included in the analysis. On day 1 of therapy, the median (interquartile range, IQR) INR was 1.4 (1.3:1.6) with 84.5% of patients having an elevated INR. The median (IQR) INR increased to 1.5 (1.4:1.6) and 1.7 (1.5:1.9) on day 4 and day 7, respectively. Of patients whose INR increased by more than 0.3, the median (IQR) change in INR from baseline was 0.5 (0.4:0.6). Apixaban is associated with a notable increase in INR in hospitalized patients, although it is not clear the clinical impact of the increase. Although literature does not support monitoring INR as a marker of apixaban activity, it is important for clinicians to understand the association apixaban has on the INR to avoid inappropriate interpretation of routine coagulation assays.

Utilization of apixaban anti-Xa levels in transition from apixaban to warfarin in a patient with chronic renal dysfunction

“…This patient’s baseline INR was 0.98 prior to initiation of apixaban and 1.84 prior to the first dose of warfarin, values that were above the median value reported in the previously mentioned study but within the observed range. 16 It is evident the presence of apixaban impacted this patient’s INR. This distinct increase in INR caused by apixaban makes using apixaban as a bridge to warfarin therapy challenging, as it is impossible to tell how much of the INR elevation is due to apixaban versus warfarin.…”

“…Apixaban therapy is not recommended during the transition due to the documented impact of oral factor Xa inhibitors on INR monitoring. 15 , 16 …”

“…Pharmacokinetic data from an institution utilizing the same instrumentation indicated a median INR of 1.4 following 1 dose of apixaban (5 mg in 72.7% of patients and 2.5 mg in 27.3% of patients), with 84.5% of patients exhibiting an elevation in INR. 16 …”

Elevated International Normalized Ratio Due to Apixaban in Patient With End-Stage Renal Disease on Hemodialysis

“…INR elevation greater than 20 is rare with apixaban when compared to rivaroxaban [ 3 ]. Median INR of 1.4-1.7 in inpatients receiving apixaban has been reported [ 5 ]. A review of patients developing hemorrhagic cardiac tamponade in setting of apixaban use showed majority of these patients had elevated INR of 1.3-5.2 and renal dysfunction [ 7 ].…”

“…Maximum concentration of apixaban is reached 1.5-3.3 hours after administration [ 4 ]. Kovacevic et al reported median INR of 1.4-1.7 in inpatient population receiving apixaban [ 5 ]. Plasma concentration of direct oral anticoagulants (DOACs) has been found to be correlating with that of the INR [ 6 ].…”