Purpose: Renal impairment, which is frequently observed in elderly patients, raises the question of low molecular weight heparins treatment dose adjustment in this population. Thus, we conducted a prospective study to determine whether tinzaparin, administered subcutaneously at treatment dose (175 anti-Xa IU/kg) once daily for 10 days, does accumulate in patients older than 70 years of age.
Methods: Accumulation criteria were an increase of plasma anti-Xa and anti-IIa levels determined prior to the first injection and on days 2, 5, 7 and 10. The characteristics of the 30 consecutive included patients receiving tinzaparin at treatment dose (six men, 24 women) were: age 87.0 +/- 5.9 years (range: 71-96 years), body weight: 62.7 +/- 14.6 kg (range: 38-90 kg) and creatinine clearance 40.6 +/- 15.3 mL/min (range: 20-72 mL/min).
Results: None of the patients required a dose adjustment of tinzaparin over the 10-day treatment period. Anti-Xa and anti-IIa activity levels on day 2 were 0.66 +/- 0.20 IU/mL (range: 0.26-1.04 IU/mL) and 0.33 +/- 0.10 IU/mL (range: 0.18-0.55 IU/mL), respectively. These levels did not significantly change over the 10 days. These results favor the absence of the accumulation effect of tinzaparin. There was no correlation between anti-Xa and anti-IIa activities and age, weight, or creatinine clearance. Concerning the side-effects, only one minor hematoma at the injection site was reported.
Conclusion: Tinzaparin may thus be administered in older patients with renal impairment, at a treatment dose (175 anti-Xa IU/kg/d) for a 10-day treatment period, without accumulation effect nor hemorrhagic side-effect in patients with creatinine clearance greater than 20 mL/min.