OC 65.1 - Prediction of apixaban or rivaroxaban concentrations based on low molecular weight heparin anti-Xa activity using nomograms: a useful tool in emergency clinical situations like thrombolysis in stroke

Background: Direct oral anticoagulants (DOACs) are now widely used for the prevention and treatment of thrombo-embolism. In emergency situations such as invasive procedures or intravenous thrombolysis in acute ischemic stroke, plasma DOAC concentration measurement may be useful for decision-making: different thresholds (30, 50, 100 ng/mL) have been proposed according to procedures. However, specific DOAC assays with rapid turnaround time are not widely available in contrast to low molecular weight heparin (LMWH) anti-Xa activity (IU/mL).

Aims: To develop nomograms to predict apixaban and rivaroxaban concentrations up to 100 ng/mL, based on LMWH anti-Xa activity.

Methods: Patients on apixaban or rivaroxaban referred to our laboratory for DOAC determination were included and separated into derivation and validation cohorts. On the same plasma sample, we measured using STA®-Liquid-Anti-Xa (Stago®): i/LWMH-anti-Xa (IU/mL; Multi-HEP®-Stago® calibrator); ii/DOAC concentrations (ng/mL) with the DOAC specific test set-up and calibrators (apixaban or rivaroxaban). Different reagent and calibrator batches were used over the study period. We built regression models from patients of the derivation cohort using R software. Model performances including sensitivity, specificity and negative predictive values for different clinically relevant thresholds are being studied on the validation cohort.

Results: Models were built from the derivation cohorts comprising 85 apixaban and 68 rivaroxaban samples. The obtained nomogram predicting apixaban concentrations (ng/mL) according to LMWH anti-Xa activity (IU/mL) is given on Figure 1. The model predicted that < 30, < 50 or < 100 ng/mL apixaban thresholds corresponded to LMWH anti-Xa values of 0.12, 0.92 and 1.63 IU/mL; it accurately predicted xaban concentrations in the validation cohort (n=67, apixaban). The validation of the rivaroxaban model is on-going.

Conclusion(s): These easy-to-use nomograms allow clinical pathologists accurately predicting apixaban and rivaroxaban concentrations in emergency situations when specific DOAC assessments are not rapidly available.