Should I use aPTT or anti-Xa levels to monitor my patient on IV heparin infusion?

Despite more than half a century of use unfractionated heparin (UFH), the optimal method to monitor its anticoagulation effect remains unclear, with arguments for and against continued use of activated partial thromboplastin time, aPTT) vs switching to antifactor Xa heparin assay (anti-Xa HA). 1-4

The advantage of aPTT include decades of use and familiarity by providers, and its relative accessibility, ease of automation and cost.1 Its disadvantages include variation among the sensitivities of different aPTT reagents as well as susceptibility to factors that do not reflect intrinsic heparin activity (eg, liver dysfunction, hypercoagulable states). 1,2 Thus patients may receive unnecessarily high or low heparin doses because of physiologic and non-physiologic influences on aPTT.

In contrast, since anti-XA HA measures the inhibition of a single enzyme (factor Xa)1, it is a more direct measurement of heparin activity, with less variability and minimal interference by certain biological factors (eg, lupus anticoagulants). Anti-Xa monitoring may also improve the time to therapeutic anticoagulation and lead to fewer dose adjustments compared to aPTT monitoring.2

The disadvantages of anti-Xa HA include inaccuracy in the setting of hypertriglyceridemia (>360 mg/dL), hyperbilirubinemia (total bilirubin >6.6 mg/dL), recent use of low molecular weight heparin, fondaparinux and direct oral factor Xa inhibitors. Its relative expense and generally less laboratory availability among healthcare facilities may also limit its use in monitoring patients on therapeutic UFH. 1-3

Somewhat unsettling is the frequent discordance between aPTT and anti-Xa values having been reported in 46% to 60% of instances that may result in either thromboembolic or bleeding complications. 1,4 One study reported that aPTT may be therapeutic only 35% of the time that anti-Xa is also therapeutic! 2

What’s clearly missing are definitive studies that can shed light on the clinical impact of these intriguing findings on patient outcomes. So stay tuned!

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References

  1. Guervil DJ, Rosenberg AF, Winterstein AG, et al. Activated partial thromboplastin time versus antifactory Xa heparin assay in monitoring unfractionated heparin by continuous intravenous infusion. Ann Pharmacother 2011;45:861-68. https://www.ncbi.nlm.nih.gov/pubmed/21712506
  2. Whitman-Purves E, Coons, JC, Miller T, et al. Performance of Anti-factor Xa versus activated partial thromboplastin time for heparin monitoring using multiple nomograms. Clinical and Applied Thromosis/Hemostasis 2018;24:310-16. https://www.ncbi.nlm.nih.gov/pubmed/29212374
  3. Fruge KS, Lee YR. Comparison of unfractionated heparin protocols using antifactory XA monitoring or activated partial thrombin time monitoring. Am J Health-System Pharmacy. 2015; 72: S90-S97, https://doi.org/10.2146/sp150016
  4. Samuel S, Allison TA, Sharaf S, et al. Antifactor XA levels vs activated partial thromboplastin time for monitoring unfractionated heparin. A pilot study. J Clin Pharm Ther 2016;41:499-502.
  5. doi:10.1111/jcpt.12415. https://www.ncbi.nlm.nih.gov/pubmed/27381025
Should I use aPTT or anti-Xa levels to monitor my patient on IV heparin infusion?