No accumulation of the peak anti-factor Xa activity of tinzaparin in elderly patients with moderate-to-severe renal impairment: the IRIS substudy

Background: In the elderly, concerns have been raised regarding the risk of accumulation of low molecular weight heparins, owing to their renal elimination. Although data exist for tinzaparin, they are observational. Objectives: To assess whether: (i) there was an accumulation of anti-factor Xa activity; and (ii) there was any relationship between anti-FXa activity and age, weight, creatinine clearance or clinical outcomes in patients with moderate-to-severe renal impairment receiving tinzaparin (175 IU kg(-1) per 24 h) for acute venous thromboembolism. Methods: In 38 centers participating in the Innohep in Renal Insufficiency Study (IRIS), peak plasma anti-FXa activity was measured on day 2/day 3 and on day 5 or at visit S (VS) (end of tinzaparin treatment). There was considered to be absence of accumulation if the 90% confidence interval (CI) of the (anti-FXa day 5/VS)/(anti-FXa day 2/3) ratio did not exceed the predefined limit of 1.25. Results: Eighty-seven patients, with a mean age of 83 +/- 5 years (range: 75-99 years) and a mean creatinine clearance (CrCl) of 40.8 mL min(-1), 24.1% of whom had severe renal impairment, were included. The mean duration of tinzaparin treatment was 8.4 days. No significant accumulation was detected: the mean accumulation ratio was 1.06 (90% CI 1.01-1.11). There was no correlation between the accumulation ratio and age, weight, or CrCl. The mean anti-FXa activity did not differ significantly between the eight patients who experienced clinically relevant bleeding and those who did not. Conclusions: No accumulation of anti-FXa activity was observed in elderly patients with renal impairment receiving therapeutic doses of tinzaparin, suggesting that there is no need for systematic anti-FXa monitoring in these patients. The high proportion of high molecular weight moieties in tinzaparin may account for its reduced dependence on renal elimination.