title: No accumulation of the peak anti-factor Xa activity of tinzaparin in elderly patients with moderate-to-severe renal impairment: the IRIS substudy.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France. virginie.siguret@parisdescartes.fr
authors.forename: V
authors.initials: V
authors.lastname: Siguret
authors.forename: I
authors.initials: I
authors.lastname: Gouin-Thibault
authors.forename: E
authors.initials: E
authors.lastname: Pautas
authors.forename: A
authors.initials: A
authors.lastname: Leizorovicz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D065427:Factor Xa Inhibitors; D005260:Female; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics*; D006495:Heparin, Low-Molecular-Weight / Q000493:pharmacokinetics*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D000078222:Tinzaparin
chemical_list: D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D000078222:Tinzaparin