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Heparin Curve to Measure DOACs?

Does your facility measure rivaroxaban or apixaban using a chromogenic substrate anti-Xa assay based on unfractionated heparin [UFH] calibrators or UFH-low molecular weight heparin [UFH-LWMH] ‘hybrid” calibrators, or do you require rivaroxaban and apixaban calibrators?

I [Geo] received a 6-22-22 response from international hemostasis expert Robert Gosselin, who cited several references. Many of us use a heparin-calibrated chromogenic substrate anti-Xa assay to detect and estimate the anti-Xa DOACs rivaroxaban and apixaban, often in ED patients who are bleeding and who are candidates for andexanet alfa reversal. The assays are also used to detect residual DOAC in patients awaiting surgery. Bob’s citations reference assays based on either UFH or LMWH-based calibration curves, none reference the UFH/LMWH [hybrid] curve, though the hybrid curve is not eliminated from consideration.

The lab’s quality control specialist focuses on the lower limit of detection [LLOD] AKA the lower limit of quantitation [LLOQ] in response to the clinical need to establish the presence or absence of the DOAC. Bob indicates that he has often seen on-therapy levels that reach or exceed the upper limit.

Several in vitro diagnostics companies make available rivaroxaban, apixaban, and edoxaban calibrators and controls. While the US FDA has approved limited kits designed to perform chromogenic anti-Xa assays based on these products, laboratory directors are not prevented from using the products to offer laboratory-developed tests [LDTs]. Likewise, the laboratory may develop and offer the ecarin chromogenic assay or the plasma-diluted thrombin time to measure the direct thrombin inhibitor dabigatran. These assays provide more accurate quantitation of the DOACs.


  • Gosselin RC, Adcock DM, Bates SM, et al. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost 2018;118:437–50.
  • Gosselin RC, Grant RP, Adcock DM. Comparison of the effect of the anti-Xa direct oral anticoagulants apixaban, edoxaban, and rivaroxaban on coagulation assays. IJLH 2016, doi:10.1111/ijlh.12528.
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