Tinzaparin and enoxaparin given at prophylactic dose for eight days in medical elderly patients with impaired renal function

Isabelle Mahé; Manvel Aghassarian; Ludovic Drouet; Claire Bal dit-Sollier; Karine Lacut; Jean-Jacques Heilmann; Dominique Mottier; Jean-François Bergmann

doi:10.1160/TH06-09-0513

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(04): 581-586
DOI: 10.1160/TH06-09-0513

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Tinzaparin and enoxaparin given at prophylactic dose for eight days in medical elderly patients with impaired renal function

A comparative pharmacokinetic study

Isabelle Mahé

¹Internal Medicine Department A, Lariboisière Hospital, Paris, France

,

Manvel Aghassarian

¹Internal Medicine Department A, Lariboisière Hospital, Paris, France

,

Ludovic Drouet

²Hematology Laboratory, Lariboisière Hospital, Paris, France

,

Claire Bal dit-Sollier

²Hematology Laboratory, Lariboisière Hospital, Paris, France

,

Karine Lacut

³Equipe Accueil, La Cavale Blanche Hospital Brest, France

,

Jean-Jacques Heilmann

⁴LEO-Pharma, Saint Quentin en Yvelines, France

,

Dominique Mottier

³Equipe Accueil, La Cavale Blanche Hospital Brest, France

,

Jean-François Bergmann

¹Internal Medicine Department A, Lariboisière Hospital, Paris, France

› Author Affiliations

Abstract

Summary

Low-molecular-weight heparins (LMWHs) accumulate in patients with impaired renal function. As this accumulation depends on heparin chain length and subsequent reticulo-endothelial/renal elimination, LMWHs might have different pharmacodynamic profiles. The primary objective was to examine if any accumulation effect of two LMWHs, enoxaparin and tinzaparin, occurred after repeated administration of a prophylactic dose over eight days in elderly patients (age >75 years) with creatinine clearance between 20 and 50 ml/min and body weight <65Kg. Patients were openly randomized to two groups (enoxaparin 4,000 IU or tinzaparin 4,500 IU once daily). Anti-Xa was measured on day 1 and day 8. Blood samples were taken at 0, 2, 4, 5, 6, 9, 12, 16 and 24 hours. The primary end point was the accumulation factor calculated as a ratio between the maximal anti-Xa activity on day 1and day 8. Fifty-five patients were included (mean age 87.9 ± 5.5 ).The creatinine clearance was 34.7 ± 11.4 ml/min; the body weight was 52.3 ± 8.6 kg. The accumulation factor defined was not significant for tinzaparin (1.05, p=0.29) while it was significantly enhanced for enoxaparin (1.22, p <0.0001). In this pharmacodynamic study performed in elderly patients with impaired renal function, a statistically significant accumulation effect was observed after eight days of prophylactic treatment with enoxaparin but not with tinzaparin, which are two LMWHs with different chain lengths. Trials based on clinical end points should be conducted to evaluate the clinical relevance of these observations.

Keywords

LMWHs - thromboprophylaxis - elderly - renal insufficiency

Full Text

References

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