Summary

Since low molecular weight heparins (LMWH) are partly eliminatedby renal excretion, their pharmacodynamic profile may be modified invery elderly patients with age-related renal impairment. The aim ofthis prospective study was to determine whether tinzaparin (Innohep ® )175 anti-Xa IU/kg administered subcutaneously once daily over10 days does accumulate in hospital patients greater than 70 years ofage. Plasma anti-Xa and anti-IIa amidolytic levels and APTT were determinedprior to the first injection (day 0), and then, at peak level i.e.5 h after the second injection (day 2) and subsequently on days 5, 7 and10.Thirty consecutive inpatients (6 men, 24 women) requiring LMWHsat a curative dose for acute thromboembolic disease were included.Patients’ characteristics (mean ± SD) were: age 87.0 ± 5.9 years (range71-96), body weight 62.7 ± 14.6 kg (range 38-90) and creatinine clearance40.6 ± 15.3 mL/min (range 20-72). The mean actual dose of tinzaparindelivered was 174.8 anti-Xa IU/kg. Since no patient had ananti-Xa activity above 1.5 IU/mL, the dose of tinzaparin remained fixedover 10 days.Anti-Xa and anti-IIa peak levels measured on day 2 were 0.66 ±0.20 IU/mL (range 0.26-1.04) and 0.33 ± 0.10 IU/mL (range 0.18-0.55), respectively. Ex vivo anti-Xa/anti-IIa ratios were close to 2.1.APTT ratios (patient/control) were strongly correlated with anti-IIa activity(p < 0.01). There was no progressive increase of the anti-Xa andanti-IIa activities after repeated administration of tinzaparin over the10 day treatment period. No correlation was found between anti-Xa andanti-IIa activities and age, weight, or creatinine clearance. No majorbleeding occurred during the study and only one minor haematoma atthe injection site was reported. No thrombo-embolic complication ordeath occurred.Tinzaparin may thus be administered safely at a treatment dose(175 anti-Xa IU/kg) in older patients with age-related renal impairment.Neither dose adjustment, nor serial anti-Xa activity monitoring seemsto be required in patients with creatinine clearance above 20 mL/minduring the first ten day treatment.