Enhanced anticoagulant activity of enoxaparin in patients with ESRD as measured by thrombin generation time

Abstract

Background: Patients with renal dysfunction who undergo systemic anticoagulation with enoxaparin are at increased risk for bleeding. Although there is decreased renal clearance of enoxaparin in this population, the clinical utility of monitoring antifactor Xa activity is controversial because it is weakly correlated to bleeding. The goal of this study was to investigate the role of other novel anticoagulation markers, such as thrombin generation time, platelet contractile force, and clot elastic modulus, while controlling for antifactor Xa activity in patients with and without renal dysfunction. Methods: Thirty anticoagulant- and antiplatelet-naive subjects completed this trial (10 controls, 10 patients with chronic kidney disease, and 10 patients with end-stage renal disease [ESRD]). Blood samples were obtained and spiked ex vivo with increasing concentrations of enoxaparin antifactor Xa activity (0.25, 0.5, 1.0, and 3.0 IU/mL). Thrombin generation time, platelet contractile force, and clot elastic modulus were measured in each group at each antifactor Xa activity concentration. Results: Subjects with ESRD had an approximately 50% greater anticoagulant effect, determined by thrombin generation time prolongation, than controls at antifactor Xa activity concentrations of 0.5 to 3.0 IU/mL. This may explain why subjects with ESRD with seemingly therapeutic antifactor Xa levels still experience adverse bleeding. There were no intergroup differences in platelet function, determined by platelet contractile force and clot elastic modulus. Conclusion: Antifactor Xa poorly predicts the degree of anticoagulation in patients with ESRD administered low-molecular-weight heparin (LMWH). Thrombin generation time may be a clinically useful anticoagulation monitoring tool to monitor LMWH therapy, especially in patients with renal dysfunction. Additional randomized prospective studies are needed to corroborate these findings.