Serial Trough Anti-Xa Levels to Assess Low Molecular Weight Heparin Accumulation in Patients with Chronic Kidney Disease: Analysis of Crcl <30 Ml/Min from the Trivet Study

Abstract Background. The predominant renal elimination of low molecular weight heparin (LMWH) has raised concerns regarding the safety of therapeutic dose LMWH in patients with renal impairment, particularly those with Cockcroft Gault creatinine clearance (CrCl) <30 ml/min. Anti-Xa levels are used a surrogate measure of bleeding risk in patients receiving LMWH, with trough levels used as a measure of LMWH accumulation. Tinzaparin may be less dependent on renal clearance compared to other LMWHs. Aims. To assess for tinzaparin accumulation in patients with venous thromboembolism (VTE) and varying degrees of renal impairment using serial trough anti-Xa level measurements. The degree of accumulation occurring in patients with CrCl <30 ml/min was further evaluated by subdividing patients with CrCl <30 ml/min into those with CrCl 20-29 ml/min and <20 ml/min. Methods. Prospective multicenter cohort study of patients with objectively confirmed VTE treated with tinzaparin (Tinzaparin in Renal Insufficient Venous Thromboembolism (TRIVET) study; NCT00186745). Informed consent was obtained and the study approved by the ethics board at each site. Patients were stratified into 4 groups based on calculated CrCl (ml/min): >60, 30-60, <30 and hemodialysis (HD)-dependent. Tinzaparin 175 IU/kg was administered subcutaneously once daily for up to 7 days. Trough anti-Xa levels were measured twice, prior to the 3rd - 5th dose and prior to the 5th - 7thdose of tinzaparin. Accumulation was defined as anti-Xa >0.5 IU/mL which resulted in a predefined dose reduction. Bleeding and recurrent thrombotic events were recorded.