PB0560 - Use of heparin-calibrated assays to estimate anti-factor Xa activity of factor Xa inhibitors (FXaI): a literature correlation analysis

Background: Measurement of drug activity in patients on direct oral anticoagulant (DOAC) therapy with FXaI (rivaroxaban, apixaban, edoxaban) may guide the management of acute complications, such as major bleeding. As specific calibrated FXaI assays are not readily available, studies have evaluated correlation between heparin-calibrated and specific FXaI assays, suggesting that heparin-calibrated assays may be suitable to assess FXaI plasma activity. LEX-210 (NCT04867837, Octapharma) will evaluate four-factor PCC (Octaplex®) in patients with acute major bleeding on FXaI and aims to include patients with baseline anti-Xa activity equivalent to ≥100 ng/mL according to the locally available test.

Aims: To enable LEX-210 investigators to convert heparin-calibrated anti-factor Xa assay results in international units (IU)/mL to equivalent DOAC concentration in ng/mL, based on correlation analysis of published data, to recruit patients.

Methods: Literature was searched (PubMed, June 2021) for original data on correlations between heparin-calibrated and FXaI-specific assays. Data from animals or spiked (not patient-derived) samples, or correlating against FXaI concentrations determined using liquid-chromatography-tandem mass spectrometry, were excluded. Fitted regression equations were extracted/calculated from included papers. Where >1 report was available for a device/reagent/FXaI combination, data were meta-analysed.

Results: 8/57 screened articles contained relevant data. Correlation curves against FXaI-calibrated anti-Xa assays were obtained for heparin-calibrated assays, for different combinations of device/reagent/calibrator. The correlation curves and corresponding conversion table for a commonly used device (STA-R coagulation analyzer) and FXaI (rivaroxaban) are shown (Figure 1/Table 1). Fewer data were available for edoxaban. Enrolment in LEX-210 is ongoing, with investigators consulting conversion tables where only heparin-calibrated assays are available.

Conclusion(s): Conversion tables based on correlation data enable clinicians to estimate FXaI plasma activity using anti-Xa assays calibrated for heparin, if FXaI-calibrated assays are unavailable. Until FXaI calibrations become more widespread, this approach may be valuable for managing patients with reversal/hemostatic agents when presenting with FXaI-related major bleeding.