April 2021 Quick Question: Andexanet Alfa Response

Thanks to our 31 participants for answering the April, 2021 Quick Question, “What test do you employ to validate the need for andexanet alfa to reverse DOAC overdose?” Here are our responses:

1. PT: 3% [1]
2. PTT: 17% [5]
3. Chromogenic anti-Xa: 77% [24]
4. DOAC Dipstick: 3% [1]

This question arose from a conversation with the director of a coagulation laboratory concerned about his emergency department’s administering andexanet alfa [Andexxa®] without confirming the presence of one of the anti-Xa direct oral anticoagulants [DOACs] rivaroxaban [Xarelto®] or apixaban [Eliquis®]. His primary concern is waste, as one administration of high-dose Andexxa costs ~$40,000, but there is also a theoretical concern for an adverse thrombotic event. The majority of respondents have access to the chromogenic anti-Xa, and in many instances, their assay is based on a heparin calibration curve. The result is considered to be semiquantitative. This is an “off-label” but essential application of the anti-Xa, and a short turnaround is necessary.

Concern for the unconfirmed administration of the reversal agent has led the American Society for Clinical Laboratory Science to draft a Choosing Wisely recommendation currently under review, “Don’t employ a specific direct oral anticoagulant [DOAC] reversal agent without identifying the DOAC and estimating its plasma concentration.”

I suspect many of us were mystified by answer #4, DOAC Dipstick®. This urine immersion device is real, developed and approved in Germany [reference below], though not currently available in North America. The DOACs dabigatran, apixaban, and rivaroxaban are excreted in urine and are easily detected by the Dipstick, which distinguishes between the anti-Xa meds and the direct thrombin inhibitor, dabigatran and provides a binary result. Click here for an article describing the DOAC Dipstick.

Though many labs offer the chromogenic anti-Xa heparin assay, not everyone has access on an emergent basis. Neither the PT or the PTT is reliable and the emergency department may find it necessary to rely on patient history.

Harenberg J, Du S, Wehling M, Zolfaghari S, Weiss C, Krämer R, Walenga J. Measurement of dabigatran, rivaroxaban and apixaban in samples of plasma, serum and urine, under real life conditions. An international study. Clin Chem Lab Med 2016; 54: 275–83.