Optimal low-molecular-weight heparin regimen in major orthopaedic surgery

Paul Zufferey; Silvy Laporte; Sara Quenet; Serge Molliex; Christian Auboyer; Hervé Decousus; Patrick Mismetti

doi:10.1160/TH03-02-0086

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(04): 654-661
DOI: 10.1160/TH03-02-0086

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Optimal low-molecular-weight heparin regimen in major orthopaedic surgery

A meta-analysis of randomised trials

Paul Zufferey

¹Anesthesiology and Intensive Care Department and the University Hospital of Saint-Etienne, France

²Clinical Pharmacology Unit, Thrombosis Research Group, University Hospital of Saint-Etienne, France

,

Silvy Laporte

²Clinical Pharmacology Unit, Thrombosis Research Group, University Hospital of Saint-Etienne, France

,

Sara Quenet

²Clinical Pharmacology Unit, Thrombosis Research Group, University Hospital of Saint-Etienne, France

,

Serge Molliex

¹Anesthesiology and Intensive Care Department and the University Hospital of Saint-Etienne, France

,

Christian Auboyer

¹Anesthesiology and Intensive Care Department and the University Hospital of Saint-Etienne, France

,

Hervé Decousus

²Clinical Pharmacology Unit, Thrombosis Research Group, University Hospital of Saint-Etienne, France

,

Patrick Mismetti

²Clinical Pharmacology Unit, Thrombosis Research Group, University Hospital of Saint-Etienne, France

› Author Affiliations

Abstract

Summary

Low-molecular-weight heparins (LMWH) are routinely used for thromboprophylaxis in major lower limb orthopaedic surgery. However the optimal LMWH regimen, offering the greatest efficacy with an acceptable risk of bleeding, has not been clearly established with regard to dose and timing of treatment initiation. We performed a meta-analysis of all available randomised trials comparing LMWH to placebo. Relative risks (RR) and corresponding 95% confidence intervals (CI) were calculated. By means of subgroup analysis, we evaluated the consistency of the results according to the timing of treatment initiation (preoperative versus postoperative) and dose of LMWH used (low doses, i.e. 4000 anti-Xa IU or below versus high doses). The possibility of a dose-effect relationship of LMWH was also evaluated by meta-regression. Thirteen studies were included (1925 patients). In four studies, LMWH treatment was started postoperatively. Daily LMWH doses ranged from 3000 anti-Xa IU to over 6000 anti-Xa IU. Compared to placebo, LMWH significantly reduced the risk of asymptomatic deep-vein thrombosis (DVT) (RR=0.51, 95% CI=[0.45-0.59], p<0.001) without significantly increasing the risk of major haemorrhage (RR=0.80 [0.36-1.79], p=0.58). We found no convincing evidence that starting prophylaxis preoperatively was associated with a significantly reduced risk of asymptomatic DVT relative to starting postoperatively. Our results showed a strong correlation between the risk of DVT and LMWH dose (meta-regression, test of slope p=0.03).These findings are tentative because the comparisons are across trials, but nevertheless suggest that the different LMWH regimens currently recommended are effective and safe.

Keywords

Deep-vein thrombosis/prevention - heparins/low-molecular-weight heparins - orthopaedic surgery - meta-analysis

Full Text

References

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