Effects of enoxaparin preparations on thrombin generation and their correlation with their anti-FXa activity

Abstract

Anticoagulant effect of LMWHs is monitored by anti-factor Xa (anti-FXa) activity assay. Since this test has several limitations, the aim of this study was to explore the activity of two LMWHs by thrombin generation assay (TG, which presents an overall picture of hemostatic balance) and its correlation with their anti-FXa activity. In an open-label, randomized cross-over study, 40 mg of two enoxaparins, the original branded formulation (R) and another one, also marketed in Argentina (T), were daily injected subcutaneously, for 7 days, to 20 healthy volunteers, with a 7-day washout interval. Blood samples were collected before treatment and 180 minutes after the injection on days 3 and 7. TG in platelet-poor plasma activated with tissue factor was assessed by lag time (LT), time to peak (TTP), peak (PTG), and endogenous thrombin potential (ETP). Anti-FXa and anti-FIIa activities, free tissue factor pathway inhibitor (free TFPI), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type 1 (PAI-1), and euglobulin lysis time (ELT) were also assayed. The mean (SD) anti-FXa (UI/ml) for T and R increased on days 3 and 7. LT and TTP were significantly prolonged by both LMWHs, with no differences between them. The mean ETP (nmol/L) for T and R at 3 and 7 days after treatment were significantly reduced when compared with basal values (p = 0.001 for all). On day 3, a significant correlation was shown between the variables describing TG and anti-FXa for T and R, without differences between them, for LT (r: 0.516 and 0486), ETP (r: 0.532 and 0.574), PEAK (r: 0.482 and 0.501), and TTP (r: 0.577 and 0.503), respectively. This correlation was also significant on day 7. Anti-FIIa activity and free TFPI increased significantly at 3 and 7 days for both LMWHs, without differences between them. R and T decreased ELT and PAI-1, but had no effect on t-PA. There were no differences between both LMWHs in routine hemostatic tests. No adverse events were reported. Correlation between TG and anti-FXa activity was good. Both enoxaparins induced similar change of coagulation parameters, with a significant increase in fibrinolytic activity.