Low molecular weight heparin for prevention of venous thromboembolism in patients with lower‐leg immobilization
Abstract
Background
Immobilization of the lower leg is associated with venous thromboembolism. Low molecular weight heparin (LMWH) is an anticoagulant treatment which might be used in adult patients with lower‐leg immobilization to prevent deep venous thrombosis and its complications.
Objectives
To investigate the current literature on thromboprophylactic practice for patients with lower‐limb injuries who are immobilized in plaster casts or braces, to assess the need for concrete guidelines, and to assess whether it is possible to come to an evidence‐based conclusion.
Search methods
The Cochrane Peripheral Vascular Disease Group searched their Specialized Register (last searched 20 May 2008) and the Central Register of Controlled Trials (CENTRAL) (last searched The Cochrane Library 2008, Issue 2). We searched MEDLINE (until May 2008) and EMBASE (until May 2008) and reference lists of articles. We contacted pharmaceutical companies of LMWHs for relevant studies.
Selection criteria
Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that described thromboprophylaxis by means of LMWH compared with no prophylaxis or placebo in adult patients with lower‐leg immobilization. Immobilization was by means of a plaster cast or brace.
Data collection and analysis
Two authors independently assessed trial quality and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager (RevMan 5).
Main results
We included six RCTs fulfilling the above criteria with a total of 1490 patients. We found an incidence of venous thromboembolism ranging from 4.3% to 40%, in patients who had a leg injury that had been immobilized in a plaster cast or a brace for at least one week and who received no prophylaxis, or placebo. This number was significantly lower in patients who received daily subcutaneous injections of LMWH during immobilization (event rates ranging from 0% to 37%; odds ratio (OR) 0.49; fixed 95% confidence interval (CI) 0.34 to 0.72; with minimal evidence of heterogeneity with an I2 of 20%, P = 0. 29). Comparable results were seen in the following subcategories: operated patients, conservatively treated patients, patients with fractures, patients with soft‐tissue injuries, patients with proximal thrombosis, patients with distal thrombosis and patients with below‐knee casts. Complications of major bleeding events were extremely rare (0.3%) and there were no reports of heparin‐induced thrombocytopenia.
Authors' conclusions
Use of LMWH in outpatients significantly reduces VTE when immobilization of the lower leg is required.
PICOs
Plain language summary
Low molecular weight heparin for prevention of venous thromboembolism in adults with lower‐leg immobilization in an outpatient setting
Immobilization of the lower limb with plaster cast or brace in adult patients is associated with deep venous thrombosis (DVT). In order to prevent this complication preventive treatment with anticoagulants is often used, most commonly low molecular weight heparin (LMWH). Different indications for the use of LMWH are given in existing national guidelines. Therefore we searched the literature for trials on this topic, in order to develop an evidence‐based stand on this matter.
Six randomized controlled trials were found and judged to be of sufficient quality to use in a meta‐analysis. The trials involved 1490 patients: 750 patients received LMWH subcutaneously once daily; 740 patients received no prophylaxis or placebo. Incidence rates of DVT ranging from 4.3% to 40% were found in the control groups and ranging from 0% to 37% in the LMWH groups. There was a significant difference (odds ratio 0.49, 95% confidence interval = 0.34 to 0.72). Further analysis showed a significant reduction of the occurrence of DVT when using LMWH in the following subgroups: operated patients; conservatively treated patients; patients with fractures; patients with soft‐tissue injuries; patients with below‐knee casts; a group with proximal thrombosis and a group with distal thrombosis.
There were few reported adverse effects in the treated patients. Two patients in the treatment group and one in the placebo group had to discontinue the LMWH due to major bleeding events. In the treatment group minor bleeding events were reported in up to 8% of cases. One patient developed facial eczema.
We conclude that LMWH should be considered in adult patients with immobilization of the lower leg to prevent occurrence of venous thromboembolism. It should not only be considered in patients with an above‐knee cast but also in patients with a below‐knee cast. LMWH can safely be used for this indication.
