In this episode, I’ll discuss the duration of DOAC interference with heparin anti-Xa levels.
DOACs that are Xa inhibitors such as apixaban and rivaroxaban interfere with heparin anti-Xa level monitoring by causing falsely elevated levels. While many references cite this interaction as lasting up to 48-72 hours, I have found many examples of a longer duration of interference in my practice.
Authors at the University of Virginia Medical Center have recently published their findings that the duration of interference can be 96 hours or even longer if there are interacting medications involved.
Their study was a retrospective review of 68 patients that were maintained on either apixaban or rivaroxaban prior to heparin initiation. The vast majority of patients, 85%, received apixaban and the remaining 15% received rivaroxaban.
In these patients, baseline anti-Xa levels were as high as 3.27 IU/mL before any heparin was given.
The authors found that the mean duration of influence was 69.3 +/- 46.2 hours, with a median duration of 62.7 hours.
Renal function and obesity did not have a significant impact on the duration of influence for the DOACs on anti-Xa levels.
However, a significant influence on test interference duration was found when looking at patients who were also taking moderate and strong inhibitors or inducers of cytochrome P4503A4 and/or p-glycoprotein.
Amiodarone, azithromycin, and diltiazem were the most common interacting medications.
At 72 hours post last DOAC dose, one-third of patients still had lab interference and it took over 100 hours before 90% of patients had no remaining anti-Xa interference.
The authors concluded:
Based on the results of the current study, it is reasonable to utilize alternative methods to h-AXA for heparin monitoring for 72 to 96 hours after DOAC discontinuation in order to minimize the risk of influence on the h-AXA in a majority of patients. This window of influence may be further extended in patients receiving interacting inhibitors. The c-AXA is a novel approach to manage this challenge by attempting to quantify ongoing DOAC influence.
Current anti-Xa level assays are chromogenic. In the presence of factor Xa inhibition, the color change of the assay can be used to determine the exact heparin level. Color change will occur regardless of whether the factor Xa inhibition comes from heparin, apixaban, edoxaban, or rivaroxaban. In a hospital that uses anti-Xa monitoring for heparin infusions, this makes for a complicated situation. To use another form of monitoring means a PTT based heparin protocol, and this means double the number of protocols for a high-risk medication. Whether the alternative mentioned by the authors of a corrected anti-Xa level can be used remains to be seen.
Members of my Hospital Pharmacy Academy have access to in-depth training from a pharmacist’s point of view on Monitoring Heparin with Anti-Xa levels, Transitioning between anticoagulants, DOAC Interactions, DOAC Reversal, Heparin Reversal, Heparin Induced Thrombocytopenia, and over 140 more practical trainings. This is in addition to many other resources to help in your practice. To get immediate access, go to pharmacyjoe.com/academy.
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