Here are the results of our August, 2018 Quick Question, answered by 93 participants:.
Stem: What is the FDA-approved assay for anti-Xa DOACs?
a. Thrombin time: 12% (11)
b. Prothrombin time: 8% (7)
c. Partial thromboplastin time: 8% (7)
d. Chromogenic anti-Xa using DOAC calibrators: 72% (68)
This was perhaps a “trick” question. The US Food and Drug Administration has never approved the chromogenic anti-Xa assay for measuring the anti-Xa DOACs despite repeated applications from several in vitro diagnostics companies, all of whom had validated calibrators and controls for rivaroxaban, apixaban, and edoxaban. So, although many facilities employ the chromogenic anti-Xa assay out of necessity, they are forced to label the assay “research use only.” Thus, answer D is technically a mislead.
Of a, b, and c, the prothrombin time is the only assay that responds adequately to the anti-Xa DOACs. Thrombin time and partial thromboplastin times’ curves are relatively flat, reflecting poor analytical sensitivity. The PT is the only assay that is FDA-approved for this purpose. So, b is correct, however the FDA approval is tacit rather than explicit, which is why I say this Quick Question could be thought of as unanswerable. Even more “tricky,” the PT responses vary in sensitivity among the various DOACs, and there is also considerable variation among the reagents and coagulometers that renders the PT semiquantitative at best.
I’ve attached the lengthy transcript of a 10/25/15 presentation (click or tap) by a number of laboratory directors, researchers, and in vitro diagnostic company representatives to FDA officials on DOAC assay needs and materials.