Elderly Patients Treated with Tinzaparin (Innohep ® ) Administered once Daily (175 Anti-Xa IU/kg): Anti-Xa and Anti-IIa Activities over 10 Days
V. Siguret (1) , E. Pautas (2) , M. Février (3) , C. Wipff (1) , B. Durand-Gasselin (4) , M. Laurent (2) , J.-P. Andreux (1) , M. d’Urso (4) , P. Gaussem (1)
From (1) Laboratoire d’Hématologie and (2) Unité de Gériatrie Aiguë, Hôpital Charles Foix, Ivry/Seine, (3) Service de Biologie and (4) Service de Gériatrie, Hôpital Notre Dame de Bon Secours, Paris, France
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.