Practical Nomogram Predicting Apixaban or Rivaroxaban Concentrations from Low-Molecular-Weight Heparin Anti-Xa Values: Special Interest in Acute Ischemic Stroke Patients

Abstract

In patients with acute ischemic stroke (AIS) using a direct oral factor-Xa anticoagulant (DOAC) during the last 48 hours, a fixed plasma heparin-calibrated anti-Xa activity (0.5 IU/mL) was proposed as a threshold below which patients could be eligible for thrombolysis and/or thrombectomy. Besides, specific DOAC-calibrated anti-Xa thresholds up to 50 ng/mL have been proposed. However, specific DOAC assays are not widely available contrarily to low-molecularweight heparin (LMWH) anti-Xa activity. We developed and validated a nomogram for predicting apixaban and rivaroxaban concentrations based on LMWH anti-Xa assay. Our prospective study included apixaban (n=325) and rivaroxaban (n=276) patients. On the same sample, we systematically measured specific DOAC concentration and LMWH anti-Xa activity, using STA®-Liquid-Anti-Xa (Stago) and specific DOAC- or LMWH-calibrators, respectively. The nomogram was built using quantifiable values for both assays on the derivation cohorts with a log-linear regression model. Model performances including sensitivity, specificity, and true positive rate for different thresholds were checked on the validation cohorts. The models built from the derivation cohorts predicted that values <30 ng/mL and <50 ng/ mL DOAC thresholds corresponded to LMWH-anti-Xa values <0.10 IU/mL and <0.64 IU/mL for apixaban; <0.10 IU/mL and <0.71 IU/mL for rivaroxaban. The model accurately predicted apixaban/ rivaroxaban concentrations in the validation cohort. This easy-to-use nomogram, developed with our reagent, allowed accurately predicting DOAC concentrations based on LMWH-anti-Xa results in emergency situations such as AIS when drug-specific assessments are not rapidly available. Using DOAC <50 ng/mL equivalent threshold, instead of the fixed LMWH <0.5 IU/mL one, would allow proposing thrombolysis to more patients.