Amy Kelley, Dahl Chase Diagnostic Services, asks, one of our hospitals had a patient on Xarelto who came in for surgery. This hospital uses STAGO Xa testing which uses a hybrid curve. The patient’s Xa should drop after 3 days. The patient was put on unfractionated heparin (UFH) while in the hospital. Our question: Should the lab be using the APTT (PTT) for unfractionated heparin monitoring after getting a baseline draw?
Hello, Amy, thank you for your question. I look forward to doing a presentation for your group in Bangor, Maine on September 12. Meanwhile, a similar thread came up on January 12, 2016 that supports the use of the chromogenic anti-Xa and then moves into a discussion of the FDA‘s failure to approve the assay for this purpose. I’m happy to learn your referring hospital is using the anti-Xa to measure Xarelto, despite the FDA‘s inaction, and I have seen some data supporting the hybrid curve for this purpose. Perhaps, until this approach is validated, the hospital lab should be advised to use a curve based on Xarelto (rivaroxaban) calibrators with rivaroxaban controls.
The January discussion doesn’t quite address your question, however. Given our current status, many facilities measure Xarelto using the PT. In theory, when switching from Xarelto to UFH, the laboratory should be able to follow the Xarelto plasma level using the PT while monitoring UFH therapy using the PTT. These are estimates at best, however, as the PT response is variable and reagent-specific, and Xarelto exerts some effect on the PTT. A better approach, though “off-label” is to use the anti-Xa to observe the diminshed levels that occur upon discontinuing Xarelto and the rise associated with UFH. I’ve heard of several facilities who are doing it this way.
Finally, to answer your question, yes, the PTT may be used to monitor UFH in this circumstance, as its response to Xarelto is minimal. It is also important to obtain a baseline prior to starting UFH, as this may help determine how much reagent-specific effect the Xarelto has on the PTT. There is a recent article (in preview) that addresses the variable reagent responses to all the DOACs: Gosselin RC, Adcock DM. The laboratory’s 2015 perspective on direct oral anticoagulant testing. J Thromb Haemost 2016; DOI: 10.1111/jth.13266. This may help.
The anti-Xa assay is far more
The anti-Xa assay is far more sensitive to rivaroxaban than to UFH, so to avoid any residual rivaroxaban effect (which at therapeutic levels yields ‘apparent UFH-activity’ way above 2U/ml if measured using an UFH calibrator), it may be prudent to use the APTT to monitor the UFH effect, but a baseline APTT is always important. More self promotion: Bonar et al. The effect of the direct factor Xa inhibitors apixaban and rivaroxaban on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples. Pathology, 2016; 48: 60–71.