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
Since low molecular weight heparins (LMWH) are partly eliminated
by renal excretion, their pharmacodynamic profile may be modified in
very elderly patients with age-related renal impairment. The aim of
this prospective study was to determine whether tinzaparin (Innohep ® )
175 anti-Xa IU/kg administered subcutaneously once daily over
10 days does accumulate in hospital patients greater than 70 years of
age. Plasma anti-Xa and anti-IIa amidolytic levels and APTT were determined
prior 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 and
Thirty consecutive inpatients (6 men, 24 women) requiring LMWHs
at a curative dose for acute thromboembolic disease were included.
Patients’ characteristics (mean ± SD) were: age 87.0 ± 5.9 years (range
71-96), body weight 62.7 ± 14.6 kg (range 38-90) and creatinine clearance
40.6 ± 15.3 mL/min (range 20-72). The mean actual dose of tinzaparin
delivered was 174.8 anti-Xa IU/kg. Since no patient had an
anti-Xa activity above 1.5 IU/mL, the dose of tinzaparin remained fixed
over 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 and
anti-IIa activities after repeated administration of tinzaparin over the
10 day treatment period. No correlation was found between anti-Xa and
anti-IIa activities and age, weight, or creatinine clearance. No major
bleeding occurred during the study and only one minor haematoma at
the injection site was reported. No thrombo-embolic complication or
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 seems
to be required in patients with creatinine clearance above 20 mL/min
during the first ten day treatment.