J Stroke.  2023 Jan;25(1):126-131. 10.5853/jos.2022.03034.

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

• Brakta C
• Stépanian A
• Reiner P
• Delrue M
• Mazighi M
• Curis E
• Siguret V

• KMID: 2539065
• DOI: http://doi.org/10.5853/jos.2022.03034

Abstract

Background and Purpose
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.
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.
Results
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.
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.

Keyword

Fibrinolysis; Stroke; Anticoagulant; DOAC; Anti-Xa; Low-molecular-weight heparin; Nomogram

Figure

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  Figure 1. Relationships between plasma LMWH anti-Xa activity (IU/mL) and apixaban (left) or rivaroxaban (right) concentration in the derivation cohort (at the top) and in the validation cohort (in the middle) and relationships between the effective measured concentration (using specific calibrators) and the DOAC concentration predicted by the model (at the bottom). Black dots, values of the derivation cohort; yellow dots, values below or above limits of quantification limits; green dots, values within the predicted interval in the validation cohort and those out (red dots); purple triangles, patients switched from apixaban to LMWH within the last three days, showing additive anti-Xa effects of both LMWH and residual apixaban in sample; blue solid line curve, the exponential relationship (dashed line 95% prediction interval); vertical yellow dashed lines, the lower and upper limits of anti-Xa quantification; horizontal yellow dashed lines, the lower limit of DOAC quantification. LMWH, low-molecular-weight heparin; DOAC, direct oral factor-Xa anticoagulant.

Reference

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