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The Need for Baseline anti-Xa Levels when Monitoring Heparin in the Direct Oral Anticoagulant Era

Posted by gulseth.michael on March 5, 2019 at 6:00 AM


By Michael P Gulseth, Pharm. D., BCPS, FASHP


DOAC to heparin transitions have become one of the more challenging issues in the modern era of anticoagulation management. I am regularly contacted (1-2 times per month) by colleagues for advice how to handle this. While even we don’t have all the answers, we have learned a few things from the literature.


Probably the most important article published on this topic is Macedo KA, et. al.  I have a link to the artilce in the reference section below.  Key findings included:


  • Studied 50 patients taking apixaban or rivaroxaban who had heparin anti-Xa levels measured before or after initiating UFH
  • Residual apixaban and rivaroxaban was found to affect the anti-Xa monitoring for up to 96 hours
  • 25% of patients developed AKI
  • Of the 28 patients were transitioned from apixaban or rivaroxaban to UFH, analysis of the initial heparin anti-Xa levels showed a supratherapeutic result (>0.7 units/mL) in 69% of patients, therapeutic result in 24% of patients, and anti-Xa levels of <0.3 units/mL (subtherapeutic) in 7% of patients
  • The authors recommended initiating UFH for patients at high risk for thrombosis once the heparin anti-Xa level was <1 unit/mL and <0.7 units/mL for patients at low risk of thrombosis, but acknowledging each case must be addressed based on underlying risk/benefit.



Another study recently published Billoir, et. al. looking at correlations of heparin calibrated Xa to the actual levels of rivaroxaban and apixaban.  (link is below)  This has validated, in my mind, the findings and recommendations of Macedo.


(Note, the articles above helped me realize it was unnecessary to draw drug specific levels in every patient…….heparin correlated anti-Xa can be adequate in some situations.  Optimally, you'll want to know the correlations on your hospital's instrumentation.)


So, it became quickly apparent that baseline anti-Xa levels are needed in the direct oral anticoagulant (DOAC) era, just as we do baseline aptt levels. When one gets into patient safety principles, it is much easier to do everything the same way on every patient rather than relying on someone to remember to do something. Many hospitals in the country have moved to this practice.


Note, if there are good reasons to NOT draw a baseline Xa, it is okay to do so. However, I would mainly only recommend that in a patient who is transiting into a hospital already on a heparin drip; for that patient, it will not provide value. In fact, if done, you will need to take an active role that a level is interpreted correctly. (example, patient bolused at outside hospital and started on a drip and shipped in. Bolus was 2 hours ago; Xa comes back at 1……..you need to make sure the drip is NOT turned down in that situation…..think about the kinetics…..)


People ask me, well what if they are NOT on a DOAC? My response is probably okay to omit the baseline anti-Xa level, but are you sure they are not on a DOAC? Is the medication reconciliation reliable? Thus, I’d rather over draw than under draw…….I view this very similar to daily INRs in the hospital which is clearly overkill most of the time, but standard practice at many facilities.


Finally, I’ve become a little concerned that many clinicians are not applying kinetics knowledge to anticoagulants (I say to our residents every day that kinetics are not just for gentamicin and vancomycin….); I can think of no more critical of a situations where you need to do this than these heparin transitions issues (and anticoagulation reversal concepts). Impossible for me to explain in a blog post, but think about the concentrations of the drugs you are dealing with on a graph (you don’t need levels to do this…..) and reason through the situation.  If you need help, simple contact me.


So, I'd love discussion if you agree/disagree with this post, as obviously much of this is my opinions on this topic!


References

Macedo KA, Tatarian P, Eugenio KR. Influence of direct oral anticoagulants on anti-factor Xa measurements used for monitoring heparin. Ann Pharmacother. 2018; 52:154–9.  https://journals.sagepub.com/doi/abs/10.1177/1060028017729481?journalCode=aopd" target="_blank">Link

Billoir, et. al. Anti-Xa Oral Anticoagulant Plasma Concentration Assay in Real Life: Rivaroxaban and Apixaban Quantification in Emergency with LMWH Calibrator. Ann Pharmacother. 2018; 52:154–9 https://journals.sagepub.com/doi/abs/10.1177/1060028018811657?journalCode=aopd" target="_blank">Link

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