A comparative in vitro study of the anticoagulant effects of branded versus biosimilar preparations of enoxaparin

Abstract

The introduction and approval of biosimilars of Low Molecular Weight Heparins (LMWH) has led to their interchangeable use with branded versions in anticoagulant therapy. Enoxaparin is an example of a LMWH, having both its branded version (Clexane®) and biosimilar versions available on the market. No studies have compared the effects of branded vs. biosimilar enoxaparin on coagulation assays. Therefore, the main aim of this study was to compare the in vitro anticoagulant effects of Clexane® and three biosimilar versions (Critinox®, Inhixa® and Qnox®), together with a World Health Organisation (WHO) Calibrator, on a panel of coagulation assays. Plasma from six first-time donors was collected and pooled into one large platelet-poor plasma (PPP) pool. PPP aliquots were spiked with five concentrations of the different enoxaparins (range 0.2 – 2.0 IU/mL). These were measured using the Chromogenic anti-Xa assay and Chromogenic anti-IIa assay. The following coagulation assays were performed in duplicates for each enoxaparin preparation: Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT), PT-derived Fibrinogen, Clauss Fibrinogen, Thrombin Time (TT), Dilute Russell’s Viper Venom Time (dRVVT) Screen and Confirm, one-stage factors VII, VIII, and IX, and chromogenic assays for factors VIII and IX. Correlation testing was carried out between increasing enoxaparin concentrations and the assay results, and One-way ANOVA/Kruskal-Wallis tests were used to detect any differences in mean results across the enoxaparins. Positive correlations were observed between increasing concentrations of enoxaparins and PT, APTT, TT and dRVVT Screen and Confirm. Negative correlations were observed with all one-stage assays and Chromogenic FVIII. No correlation was observed for the fibrinogen assays and Chromogenic FIX. This study concluded that branded and biosimilar versions of enoxaparin exhibited very similar in vitro anticoagulant effects across the coagulation assay panel tested.