Tinzaparin for venous thromboembolism in patients with renal impairment - a single-centre, prospective pilot study.

Low molecular weight heparins (LMWH) are used extensively for prophylaxis and treatment of venous thromboembolism (VTE), bridging therapy for warfarin, and standard of care in cancer-associated VTE. Tinzaparin has the highest molecular weight of all LMWH, and relies least on renal clearance to Cockcroft-Gault creatinine clearance (CrCl) of 20ml/min. Previous pharmacological studies have demonstrated safety and effectiveness in elderly patients. Prospective clinical trials have confirmed these findings to CrCl 20ml/min and in cancer-associated VTE. We describe the pilot program developed at Concord Repatriation General Hospital for tinzaparin. Twenty patients were established on tinzaparin as therapeutic anticoagulation with CrCl or CKD-EPI estimated glomerular filtration rate (eGFR) 20-50ml/min with an indication for anticoagulation. Tinzaparin anti-Xa levels were tested at days 2, 7 and 14 (+/- one day) and transition to oral anticoagulants were allowed at clinician discretion. No accumulation of tinzaparin was seen into day 14. Two patients required dose-adjustment, five patients had bleeding complications (two major, three minor), and four patients died during follow-up, all attributable to patients' comorbidities. CrCl and BSA-standardised CrCl were significantly correlated with tinzaparin anti-Xa level only on day 2, and this effect was lost when patients with CrCl >50ml/min were excluded. Data from our cohort confirms previous pharmacokinetic studies using therapeutic tinzaparin in patients with CrCl or CKD-EPI eGFR 20-50ml/min with no signs of accumulation. Bleeding and death outcomes were also comparable to other trials using tinzaparin in cancer-associated VTE. Tinzaparin is an attractive alternative anticoagulant with once-daily administration in a range of potential indications. This article is protected by copyright. All rights reserved.