August, 2018 Quick Question

August, 2018 Quick Question
Sep 2, 2018 6:47pm

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.

1 Comment

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.

By Dr Paul Riley
Sep 10, 2018 1:59pm
Hi George. The PT is not actually approved for DOAC measurement. Use of PT for measurement of rivaroxaban would be considered off label. The only on label application of clotting tests currently available would be thrombin time for dabigatran and other direct thrombin inhibitor screening assuming the intended use or other summary statement on the labeling lists direct thrombin inhibitor screening. Some of the PT reagents are not actually very responsive to rivaroxaban, but most are sensitive. In addition, neither the PT or aPTT are sensitive to apixaban. See the following for more.

Cuker A, Siegal DM, Crowther MA, Garcia DA. Laboratory measurement of the anticoagulant activity of the non-vitamin K oral anticoagulants. J Am Coll Cardiol 2014; 64: 1128-39.

Samama MM, Martinoli JL, LeFlem L, Guinet C, Plu-Bureau G, Depasse F, et al. Assessment of laboratory assays to measure rivaroxaban--an oral, direct factor Xa inhibitor. Thromb Haemost 2010; 103: 815-25.

Barrett YC, Wang Z, Frost C, Shenker A. Clinical laboratory measurement of direct factor Xa inhibitors: anti-Xa assay is preferable to prothrombin time assay. Thromb Haemost 2010; 104: 1263-71.

Asmis LM, Alberio L, Angelillo-Scherrer A, Korte W, Mendez A, Reber G, et al. Rivaroxaban: Quantification by anti-FXa assay and influence on coagulation tests: a study in 9 Swiss laboratories. Thromb Res 2012; 129: 492-8.

Douxfils J, Chatelain C, Chatelain B, Dogné JM, Mullier F. Impact of apixaban on routine and specific coagulation assays: a practical laboratory guide. Thromb Haemost 2013; 110: 283-94.

Leave A Comment

You must be logged in to Comment - Sign In