Immobilization and the risk of venous thromboembolism. A meta-analysis on epidemiological studies

doi:10.1016/j.thromres.2009.05.006

Thrombosis Research

Volume 124, Issue 4, September 2009, Pages 468-476

https://doi.org/10.1016/j.thromres.2009.05.006 Get rights and content

Abstract

Background

The thrombogenic burden of immobilization remains unknown especially in the medical setting. Most of epidemiological studies estimating the link between risk factors and venous thromboembolism (VTE) have not been designed to evaluate immobilization. The aim of this work was to estimate the risk of VTE in medical bedridden patients by a systematic review and a meta-analysis.

Methods

A research on PUBMED and EMBASE was carried out to retrieve case-control and cohort studies showing the proportion of bedridden patients with or without VTE. Included studies were assigned in six groups according to the following criteria: 1) their design (cohort or case-control), 2) the targeted population (with or without suspicion of VTE) and 3) the medical setting (ambulatory or hospital). Odd-Ratios and Relative Risk for case-control and cohort studies were calculated using a random effect method. Heterogeneity and publication bias were statistically assessed by the I² statistics and funnel plots with Egger's tests.

Results

43 studies were included (24181 patients). The pooled RR ranged from 1.46 to 2.77 in the subgroups of cohort studies (n = 36) with an overall RR of 1.86 (1.61-2.14; P < 0.001). The pooled OR were 2.79 and 2.47 in the two subgroups of case-control studies (n = 7), both statistically significant (overall OR: 2.52; 1.70-3.74; P < 0.001). Heterogeneity through studies was demonstrated in four subgroups. Publication bias was only observed in one subgroup.

Conclusions

Among medical patients, immobilization increases the risk of VTE. Nevertheless, a specific role of underlying conditions can not be excluded.

Introduction

Based on pathophysiological arguments, immobilization has been suspected of being a risk factor for venous thromboembolism (VTE). The supine position can lead to a muscular and diaphragm dysfunction which decreases the venous flow in the legs and causes “venous stasis”. Venous stasis may in turn induce an hypercoagulability state, by activating the extrinsic pathway of coagulation via hypoxemia, and also by producing endothelial damage [1], [2] or by reducing the fibrinolytic activity [3], [4]. In clinical settings, thrombogenic effects of bedrest remain discussed. In the recent literature, conflicting results are reported going from clear thrombogenic effects [5] to non significant trends [6]. These discrepancies highlight difficulties in analyzing and extrapolating data from epidemiological studies in this context. Indeed, in order to compile results in a comprehensive review, numerous methodological parameters have to be taken into account such as the design of the study (cohort or case-control studies, retro or prospective studies), the study population (ambulatory or hospitalized patients), the exact definition of immobilization and the procedure for venous thrombosis assessment. Moreover most of the epidemiological studies which analyze the link between risk factors and VTE have not been designed and powered to evaluate the real effect of immobilization. When a link has been established, it seemed often impossible to dissociate the specific effect of bedrest from the effect induced by the underlying conditions which may have precipitated immobilization. Prospective studies, theoretically needed to demonstrate an independent role, are very difficult to carry out, especially because of the number of patients required.

However, despite the lack of data concerning the link between bedrest and VTE, bedrest is actually recognized as a necessary but not sufficient condition to initiate a preventive treatment in current guidelines for VTE prevention [7].

Meta-analysis may overcome some of the methodological issues in publications addressing the risk associated with immobilization. In particular, it provides a better methodological strength by increasing the number of included patients.

The objective of this study was, in the medical setting, to evaluate the risk of deep vein thrombosis in ambulatory or hospitalized bedridden patients by a systematic review and a meta-analysis of epidemiological studies.

Section snippets

Criteria of considered studies

Only case-control or cohort studies were considered, regardless of their retrospective or prospective design. Case reports and reviews were excluded from this analysis.

Hospitalized patients and ambulatory patients were considered separately in this analysis. All validated strategies which enable to confirm or exclude deep vein thrombosis (DVT) or pulmonary embolism (PE) were accepted. Only studies aiming at evaluating recent (less than one month) medical immobilization, regardless of the

Review procedure (cf. Fig. 1)

3100, 2648 articles and 1613 occurrences, respectively, were identified during the three steps of the review strategy. Among the 199 articles entirely recovered and read, 52 were retained according to the inclusion and exclusion criteria and submitted to the second reading. Other exclusion criteria, not previously detected, were found in nine studies during the rereading.

Methodological characteristics of the included studies (cf. Table 1)

Finally, 43 studies accounting for 24181 patients were selected, summing 1498 immobilized patients within 5479 patients with

Main Results

This meta-analysis conducted in medical non-selected patients was based on a systematic review of epidemiological studies using the two main databases for medical clinical research (PUBMED and EMBASE). The main result is that immobilization increases significantly the risk of venous thromboembolism with a risk of VTE about two times higher in immobilized patients than in patients with a normal walking.

Generalisability-external validity

This result must be carefully taken into account, in the four subgroups where the

Acknowledgements

Dr Neeltje Steeghs for his kindly contribution to a better exhaustiveness of this meta-analysis letting us knew the details of his work.

GlasgowSmithKline (GSK) for its financial support.

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The NMOSD population may be at risk for VTE due to the following factors. First, immobilization is an important factor in the increased risk of VTE (Pottier et al., 2009). In NMOSD patients, transverse myelitis (TM) is one of the core clinical characteristics and causes sudden paraplegia during acute attack.
Neuromyelitis optica spectrum disorders (NMOSD) patients may be at increased risk of venous thromboembolism (VTE) during the acute attack, but evidence is limited.
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We conducted a retrospective study of NMOSD patients with an acute attack between January 1, 2015, and June 31, 2021. Diagnosis of DVT or PE was objectively confirmed by doppler ultrasound or computed tomographic pulmonary angiography (CTPA) during their acute hospital stay.
We identified 184 attacks in 128 NMOSD patients with the mean age of 46.9 years at the time of the attack and female predominance (152/184, 83.2%). VTE occurred in 22 (12.0%) attacks. Among the 22 attacks, 20 presented with transverse myelitis (TM), 1 cerebral syndrome (CS), and 1 simultaneous TM and brainstem syndrome (BS). Multivariable logistic regression analysis showed that advanced age [odds ratio (OR) = 1.08, 95% confidence interval (CI) = 1.04–1.12, p = 0.000], Nadir Expanded Disability Status Scale (EDSS)>6.5(OR = 3.39, 95% CI = 1.22–10.10, p = 0.029) and intravenous immunoglobulin (IVIG) treatment (OR = 3.21, 95% CI = 1.15–8.91, p = 0.025) were independent risk factors for the development of VTE in the total NMOSD cohort. In the subgroup analysis of the NMOSD patients with TM, age at attack (OR = 1.07, 95% CI = 1.03–1.11, p = 0.002) and IVIG treatment (OR = 4.23, 95% CI = 1.44–12.45, p = 0.009) were independent risk factors for the development of VTE in the total NMOSD cohort, but Nadir EDSS>6.5 was not an independent risk factor.
VTE is a frequent complication in NMOSD patients, especially in patients with TM. Advanced age and IVIG are independent risk factors for VTE. Immobilization is an independent risk factor for VTE in the total NMOSD cohort but not in the subgroup analysis of the patients with TM.
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Few studies have been able to disentangle the effect of immobilization from that of hospitalization, and hospitalization has frequently been used as a proxy for immobilization when studying the risk of VTE, as high-quality data on immobilization is often lacking. A previous meta-analysis on immobilization and VTE-risk among hospitalized inpatients reported a relative risk of 1.5 across 7 cohort studies and an OR of 2.5 across 3 case-control studies [10]. In our study, hospitalization with immobilization was 3-times more common prior to a VTE than hospitalization without immobilization, supporting that immobilization contributes substantially to the risk of VTE among hospitalized patients.
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Regular ArticleImmobilization and the risk of venous thromboembolism. A meta-analysis on epidemiological studies

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Criteria of considered studies

Review procedure (cf. Fig. 1)

Methodological characteristics of the included studies (cf. Table 1)

Main Results

Generalisability-external validity

Acknowledgements

Biochim Biophys Acta

Blood

Ann Vasc Surg

Control Clin Trials

Chest

J Thromb Haemost

Thromb Res

Am J Med

J Vasc Surg

Ann Emerg Med

J Thromb Haemost

Thromb Res

Med Clin (Barc)

Lancet

Am J Med

Rev Med Intern

J Thromb Haemost

Hypoxia/Hypoxemia-Induced activation of the procoagulant pathways and the pathogenesis of ischemia-associated thrombosis

Arterioscler Thromb Vasc Biol

The association between seated immobility and local lower-limb venous coagulability in healthy adult volunteers: a simulation of prolonged travel immobility

Blood Coagul Fibrinolysis

A simplified clinical model to predict pulmonary embolism in patients with acute dyspnea

Int Heart J

A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients

N Engl J Med

Measuring inconsistency in meta-analysis

BMJ

Summing up: the science of reviewing research

Bias in meta-analysis detected by a simple graphical test

BMJ

Sbe26: Assessing the influence of a single study in meta-analysis

Stata Tech Bull

Controlling the risk of spurious findings from meta-regression

Statistics in Medicine

Systematic reviews in health care. Assessing the quality of controlled clinical trials

BMJ

Risk assessment of pulmonary embolism by multivariate analysis

Arch Surg

Pulmonary embolism in very old patients

Aging Clin Exp Res

Regular Article
Immobilization and the risk of venous thromboembolism. A meta-analysis on epidemiological studies