Unresponsiveness of Activated Partial Thromboplastin Time to Bivalirudin in Adults Receiving Extracorporeal Membrane Oxygenation

Author:

Jatis Andrew J.1,Nei Scott D.2,Seelhammer Troy G.3,Mara Kristin C.4,Wieruszewski Patrick M.23ORCID

Affiliation:

1. From the Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois

2. Department of Pharmacy, Mayo Clinic, Rochester, Minnesota

3. Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota

4. Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota.

Abstract

Activated partial thromboplastin time (aPTT) is the standard for monitoring bivalirudin but demonstrates a nonlinear response at higher drug concentrations. The objective of this study was to assess the relationship between bivalirudin dose and aPTT in patients receiving extracorporeal membrane oxygenation (ECMO) to determine a threshold where aPTT unresponsiveness occurs. Two hundred fourteen adults receiving bivalirudin during ECMO between 2018 and 2022 were included. Piecewise regression in a linear mixed effects model was used to determine a bivalirudin dose threshold of 0.21 mg/kg/hr for aPTT unresponsiveness. For doses of less than 0.21 mg/kg/hr (n = 135), every 0.1 mg/kg/hr dose increase led to an aPTT increase of 11.53 (95% confidence interval [CI] = 9.85–13.20) seconds compared to only a 3.81 (95% CI = 1.55–6.06) seconds increase when dose was greater than or equal to 0.21 mg/kg/hr (n = 79) (p interaction < 0.001). In multivariable logistic regression, venovenous configuration (odds ratio [OR] = 2.83, 95% CI = 1.38–5.77) and higher fibrinogen concentration (OR = 1.22, 95% CI = 1.05–1.42) were associated with greater odds of unresponsiveness, whereas older age (OR = 0.79, 95% CI = 0.63–0.98), kidney dysfunction (OR = 0.48, 95% CI = 0.25–0.92), and a higher baseline aPTT (OR = 0.89, 95% CI = 0.82–0.97) were associated with lower odds. Alternative methods are necessary to ascertain bivalirudin’s hemostatic impact when doses exceed 0.21 mg/kg/hr during ECMO.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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