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

Abstract

Background and PurposeIn 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. Methods 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. ResultsThe 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. Conclusions 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.

Coagulation assays and direct oral anticoagulant levels among patients having an elective surgery or procedure

“…Efforts should be undertaken to increase the availability of DOAC‐specific calibrators and reduce unnecessary preprocedural coagulation testing among DOAC‐treated patients. Nomograms that make use of widely available low molecular weight heparin (LMWH) anti‐Xa activity measurements to estimate apixaban/rivaroxaban levels <100 ng/ml might prove useful in these situations 21 . Similarly, LMWH anti‐Xa cutoff values might be of use to identify patients with apixaban/rivaroxaban levels below clinically relevant thresholds (<30–50 ng/ml) 22 .…”

“…Nomograms that make use of widely available low molecular weight heparin (LMWH) anti-Xa activity measurements to estimate apixaban/rivaroxaban levels <100 ng/ml might prove useful in these situations. 21 Similarly, LMWH anti-Xa cutoff values might be of use to identify patients with apixaban/ rivaroxaban levels below clinically relevant thresholds (<30-50 ng/ ml). 22 It is worth noting that the clinical significance of DOAC levels <30-50 ng/ml with respect to procedural hemostasis is uncertain.…”

Challenges to Laboratory Monitoring of Direct Oral Anticoagulants

“… 59 , 62 The requirements of additional cost and laboratory expertise may limit widespread implementation and use in all clinical settings on a 24/7 basis. 63 Best practice incentives to reduce cost and/or educate both physicians and clinical laboratory scientists may help overcome implementation barriers.…”

Effectiveness and safety of rivaroxaban for anticoagulation therapy in COVID-19

“…Rivaroxaban is an oral inhibitor of Factor Xa approved for venous thromboembolism prophylaxis and treatment, as well as for stroke prophylaxis in non-valvular atrial fibrillation (NVAF). 12 , 13 There is limited high-quality literature on the use of rivaroxaban as an anticoagulant in patients with COVID-19. 10 , 11 Recently, there have been inconsistent conclusions on the effectiveness and safety of rivaroxaban in COVID-19 patients based on randomized controlled trials (RCTs).…”