In this episode, I’ll discuss using Anti-Xa vs. aPTT for heparin infusion monitoring.
Over the past several years, many institutions have switched to monitoring heparin infusions with anti-factor Xa levels instead of activated partial thromboplastin time.
Guidelines
Expert guidelines don’t seem to take a stand either way when it comes to anti-Xa vs. aPTT for heparin monitoring. Chest guidelines and ACC/AHA guidelines don’t make a recommendation. With the increased popularity of anti-Xa, I expected the updated 10th edition CHEST guidelines to touch on the subject, but they are silent on it.
Each institution that uses aPTT to measure heparin has a unique therapeutic range. This is due to the way therapeutic aPTT is determined. The aPTT range is actually calibrated based on samples of anti-Xa levels! Samples are tested, and aPTT values are plotted against a therapeutic anti-Xa range of 0.3 to 0.7 IU/mL. The best fit line is then used to determine the aPTT range that correlates to the actual therapeutic anti-Xa range. The aPTT is, in fact, a relatively crude proxy for the anti-Xa level!
A given heparin level reliably corresponds to an anti-Xa level. This was surprising to learn since I have always considered heparin a finicky drug to get within therapeutic range. I attributed this to heparin following zero-order kinetics, but it turns out it is the aPTT that is finicky, not the drug!
Benefits of using anti-Xa
The main benefits of monitoring heparin by anti-Xa are said to be:
– Better correlation to actual heparin level
– Better defined target that won’t change with each reagent batch (anti-Xa level of 0.3-0.7 IU/mL)
– Less interference from hemolysis, warfarin, liver disease
The disadvantages of anti-Xa are disappearing since the test can now be inexpensively available on a 24/7 basis.
Evidence
The final limitation is the level of evidence available to support using the anti-Xa level rather than aPTT to monitor heparin infusions.
Double-blind controlled studies comparing the two strategies are lacking. Here are some notably published articles on the topic:
“”Anti-Xa was associated with a significant reduction in RBC transfusions when compared to patients monitored by aPTT alone. This article is protected by copyright. All rights reserved.
Patients with cirrhosis are at higher risk for both bleeding and thrombosis-related complications. Cirrhosis affects production of both procoagulant and anticoagulant factors, thus resulting in increased INR and aPTT levels and decreased anti-Xa levels.
The time to achieve therapeutic measures and bleeding outcomes were not significantly different between anti-Xa and aPTT nomograms. However, a small study size limits the power to detect clinically relevant differences. The results warrant larger prospective studies of UFH monitoring in children with thromboembolic disease.
Use of an anti–factor Xa assay–based UFH-monitoring protocol resulted in a higher percentage of within-range blood plasmaheparin monitoring tests, fewer monitoring tests for the patient to achieve blood plasma monitoring tests within goal range, and fewer dose adjustments compared with a protocol based on blood plasma monitoring using the aPTT.
Given that several biologic factors can influence the aPTT independent of the effects of UFH, many institutions have transitioned to monitoring heparin with antifactor Xa levels, rather than the aPTT. Clinical data from the last 10-20 years have begun to show that a conversion from aPTT to antifactor Xa monitoring may offer a smoother dose-response curve, such that levels remain more stable, requiring fewer blood samples and dosage adjustments. Given the minimal increased acquisition cost of the antifactor Xa reagents, it can be argued that the antifactor Xa is a cost-effective method for monitoring UFH.
Conclusion
Despite the lack of a “gold-standard” trial, I don’t think there should be too much controversy switching from aPTT to anti-Xa monitoring since the therapeutic aPTT range was always pinned to the anti-Xa level in the first place. Let me know your thoughts in the comment section below:
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
Hey Pharmacy Joe — Loved this topic. It has really come to light in my institution in recent months. We first had a run of falsely elevated Xa-levels due to recent use of the Xa inhibitor NoACs (which I briefly talked about in the slack group). Then in the last few weeks, we had a weird run of normal Xa (in range), but >max aPTT results, one of which ended in a expiration due to bleeding. As a pharmacist and still licensed medical laboratory scientist, this has been quite intriguing. I think many of my pharmacist colleagues would immediately jump to the conclusion that it must be an analytical error, but in all cases it was not.
I have found that many pharmacists are not comfortable with understanding how the tests are done, and therefore find it challenging to consider less common factors that would give unexpected results. This makes for difficult monitoring. Ive also found that many physicians also do not fully understand the testing as well. I referred these issues to out clinical pathologist (who happens to specialize in coagulation testing) to better understand what was going on. And even in those cases, he had to look some things up. I think the bottom line is that currently there is no good studies or solid evidence as to what are some of the new issues with heparin monitoring. The data is starting to build though, we just need to synthesize it into a useable form for practicing pharmacists.
There are 2 great webinars presented by Diagnastico-Stago on the subjects. If you are interested feel free to contact me and I will direct you to them.
I apologize for being brief with my “case reports” earlier in this post, but if anyone would like more info and to discuss them, please feel free to contact me!
Nice episode.
But I do not get well why guidelines recommend it then? antiXa is still about 10 times the price of aPTT @ our hospital in the Netherlands for example. If there is “no proven benefit”…
There was an econ study done showing that while it was more expensive to run, the money and nursing/lab time you save by switching to anti-Xa makes it “cheaper” because you become therapeutic faster and you need fewer lab draws.
Thanks for the post, Joe.
I have had similar experiences to Chris. During residency we were using anti-Xa exclusively (and generally did not check aPTTs at all for heparin). We had a patient who accidentally had an aPTT checked and it happened to be elevated though the anti-Xa was therapeutic. It was decided to ignore the aPTT and keep using the anti-Xa and the patient developed a massive ICH and died.
They did a QA and found a number of patients with discordant results (some were the opposite trend with a low aPTT and therapeutic/elevated anti-Xa). In the end they switched back to aPTT monitoring and I think still use that.
None of this proves anything (that patient I mentioned may have bled regardless) but I think there is still some unanswered questions about what those discordant values mean and who is at risk for bleeding events.
At my current institution we use aPTT routinely but may use anti-Xa in select cases.
Justin
Ran across this “blog” over 3 years after it was posted. May be too late in the game to post, but thought I would give my opinion. We are currently changing to anti-Xa for monitoring heparin therapy, and so I spent the last year researching this subject. One of the first articles I came across was from Stanford published in 2013. This was a retrospective study involving over 500 patients in which they drew concurrent aPTTs/anti-Xa levels and tried to make a comment on the discordance between the two. Basically one of the most important findings of the study was that patients who had two consecutive discordantly high aPTTs (unfortunately not well defined in the article) relative to the anti-Xa had a three-fold increase in major bleed rate and 30 day mortality.
The Stanford study seems to parallel the two comments of patient deaths when only using anti-Xa to monitor therapy. Stanford’s conclusion for the study indicated that at that time they would recommend drawing both anti-Xa and aPTT levels in order to expose this type of patient. Whereas they continued to utilize anti-Xa therapy only to monitor and adjust heparin therapy during the study period, they saw a negative impact on this type of patient who had significant discordance between the anti-Xa and aPTT levels.
Why would this happen? I’ll explain my opinion on the next post.
If you look at the biochemical appraisal of the aPTT, you will find it provides a better global assessment of the effect of heparin on a patient’s coagulation system. Whereas the anti-Xa only reflects heparin’s activity relative to factor Xa, the aPTT measures the influence of the heparin on factors II, VIII, IX and X, providing a better overall picture of heparin’s effect on the patient’s coagulation system.
I hope you will begin to see the problem with just monitoring heparin therapy with anti-Xa (representing heparin levels) versus the aPTT (measuring the response of the patient to the heparin).