Article Text

Guidelines in Emergency Medicine Network (GEMNet): guideline for the use of thromboprophylaxis in ambulatory trauma patients requiring temporary limb immobilisation
1. Catherine Roberts,
2. Daniel Horner,
3. Grant Coleman,
4. Laura Maitland,
5. Thomas Curl-Roper,
6. Rachel Smith,
7. Ellena Wood,
8. Kevin Mackway-Jones
1. Emergency Department, Manchester Royal Infirmary, Manchester
1. Correspondence to Dr Catherine Roberts, Emergency Department, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Trust, Sharoe Green Lane, Fulwood, Preston PR2 9HT, UK; Catherine.roberts{at}lthtr.nhs.uk

## Abstract

▸ The Guidelines in Emergency Medicine Network (GEMNet) has been created to promote best medical practice in a range of conditions presenting to emergency departments (EDs) in the UK.

▸ This guideline presents a summary of the best available evidence to guide the use of thromboprophylaxis in adult ambulatory outpatients who present to the ED following acute limb trauma and require temporary immobilisation.

▸ The document has been developed following discussion among emergency physicians and collegiate fellows to decide which topics would benefit from the development of clinical guidelines.

▸ The document is intended as a guideline for use in the ED by emergency physicians and is based on the review of the best existing evidence for treatments used in this setting.

▸ The document is summarised as a Clinical Decision Support Guideline that has been presented as an easy to follow algorithm.

▸ The intention is for each guideline to be updated and reviewed as further evidence becomes available. The formal revision date has been set at 5 years from publication, though the guideline is subject to continuous informal review.

• Emergency Care Systems
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## Introduction

### Responsibility for development

This document has been developed in response to a perceived need to improve clinical effectiveness for care in this field, in addition to the call for routine risk assessment through recent National Institute of Clinical Excellence (NICE) guidance.1 The intention is to distil information from the medical literature into practical advice for clinicians working in the department. The information is presented in the form of a Clinical Decision Support Guideline available on the shop floor in the form of a Clinical Decision Support Manual and on individual A4-sized forms.

### Funding

Funding for the development of this guideline was received from the College of Emergency Medicine.

### The Guideline Working Group

A Guideline Working Group met to discuss this condition and decide on the clinical questions, consider the evidence available and develop the recommendations. Due process ensured that the working group had access to the relevant information and the required resources in order to develop in a constructive manner.

The guideline has been developed in accordance with the principles described by the National Institute for Health and Clinical Excellence guideline development methods.2

## Topic introduction

The relationship between temporary limb immobilisation and venous thromboembolism (VTE) has been documented since 1944.3 This link persists despite modern medical care, with lower limb immobilisation recently implicated as an aetiological factor in approximately 1.5–3% of all VTE events.4 ,5 The actual incidence of VTE in patients with temporary plaster immobilisation is estimated anywhere between 5% and 39%, depending on the type of patient and the type of immobilisation.6–10 When compared with an annual VTE incidence of 0.12–0.18% in a normal undifferentiated population, these figures serve as a stark reminder of risk.11–13

The concept of prescribing thromboprophylaxis to ambulatory patients in temporary immobilisation is not a novel one. Prophylaxis is commonplace in some European countries,14–16 being recommended in national guidance from both the French and German Medical Societies.17 However, contemporary literature would suggest that UK and American practice does not mirror that seen within Europe. A recent UK national survey indicates that over 60% of departments do not routinely use thromboprophylaxis. In those that do there is little agreement as to the practicalities of administration.18 ,19

The lack of consensus decision making for this cohort is likely, in part, due to an absence of clear guidance. Although the Department of Health recently highlighted VTE prevention as a clinical priority, implementing a national programme20 and producing NICE guidelines regarding the indications and use of thromboprophylaxis in inpatients,1 advice regarding outpatient therapy is scant. In relation to the use of thromboprophylaxis in patients with temporary immobilisation, guidance is limited to a single sentence, which provides no practical advice for shop floor clinicians.

A further barrier to consideration and implementation stems from the failure to recognise VTE as a significant problem within this cohort of patients. There is evidence to suggest clinicians often consider serious VTE to be rare within this group, despite regular published reports within the medical literature21 ,22 and national media.23 ,24 Additionally, a significant proportion of VTE events documented following temporary immobilisation are distal calf thrombi.9 ,25 ,26 Equipoise remains regarding the management of distal deep vein thrombosis (DVT).27 ,28 However, this does not mean that the condition is without risk of serious morbidity. Propagation rates as high as 39% have been demonstrated with conservative management, and embolisation has been reported within a single week.29 ,30 In addition, a real potential of subsequent post-thrombotic syndrome exists.31

This guideline seeks to address the gap in UK national guidance, applicable to emergency physicians, with regard to the use of thromboprophylaxis in ambulatory trauma patients with temporary limb immobilisation. We aim to summarise and distil the relevant evidence with regard to the prevention of VTE in this cohort of patients, with the goal of providing a structured treatment pathway, and this has been presented as a series of clinical questions, which have been answered using the previously described Best BETs methodology.32

This guideline does not aim to replace previous advice but to present a complementary structured guideline and evidence-based flowchart to aid the decision-making process for these patients within the emergency department (ED). It is hoped that this will help to optimise and standardise the care delivered to this group.

## Scope

This guideline encompasses adult patients (>16 years of age) presenting to the ED with ambulatory limb trauma suitable for temporary limb immobilisation and community follow-up. The guideline excludes all hospital inpatients, the majority of whom will be prescribed thromboprophylaxis as standard. The key aspects of the guideline include evidence-based assessment of the incidence and nature of VTE, individualised risk assessment, prophylaxis options and risks associated with prophylactic anticoagulation. The initial assessment and management recommendations can be followed using resources available in any UK ED. Disposition, follow-up and ongoing care may vary depending on local resources, but the guideline may be adapted as appropriate.

This document does not provide guidance regarding patients less than 16 years of age, patients with multiple injuries, hospital inpatients or those with complex haematological issues. The use of physical or limited availability treatments such as intermittent pneumatic compression devices is also excluded because of limited availability throughout the country and applicability to the patient with lower limb immobilisation.

## Methodology

This guideline was developed using a novel methodology that has recently been used in cardiothoracic surgery.33 Many guidelines perform a single systematic review of the literature in order to answer all of the relevant clinical questions. In order to maximise sensitivity, we performed a separate shortcut systematic review of the literature for each clinical question identified.

Guideline development was structured into several stages. Initially the two lead guideline developers (CR and DH) met to discuss the scope of the guideline and to identify all clinical questions that may have been relevant. To answer the clinical questions identified, we performed a series of structured shortcut systematic reviews (Best BETs), the principles of which have been previously described.32

Having gathered and collated the evidence for each clinical question, the principle guideline developers met to create a series of guideline recommendations, which were used to create an evidence-based flowchart. Following consultation with the senior author (KMJ), modifications were made before the final guideline was agreed upon.

### Levels of evidence and grading of recommendations

Studies included in this guideline were graded for level of evidence according to previously accepted definitions.34 In summary, level 1 evidence comes from well-designed randomised controlled trials (RCTs), level 2 evidence from large cohort studies or poorly designed RCTs, level 3 evidence from small cohort studies or case–control studies and level 4 evidence from experimental studies, case series or case studies. The suffix ‘a’ implies that evidence at this level is from systematic review or meta-analysis, whereas the suffix ‘b’ implies that the evidence is from original research.

The recommendations that have been made were graded according to the level of evidence upon which they were based:

• Grade A: based on multiple level 1a or 1b papers.

• Grade B: based on individual level 1a or 1b papers or multiple level 2a or 2b papers.

• Grade C: based on individual level 2a or 2b papers or multiple level 3a or 3b papers.

• Grade D: based on individual level 3a or 3b papers or level 4 papers.

• Grade E: based on consensus guidelines or studies of expert opinion.

### Definitions of thromboprophylaxis and immobilisation

For the purposes of this guideline, thromboprophylaxis is defined as any anticoagulant therapy administered by any route at a dose considered to be prophylactic, rather than therapeutic, for the patient concerned.

Immobilisation is defined as any clinical decision taken to manage the affected limb in such a way as to prevent normal weight-bearing status and/or use of that limb.

Transient/temporary risk refers to a provoking risk factor, with a definitive temporal association. Permanent risk refers to an ongoing risk factor with no definitive time period of association or clear cessation date.

VTE refers to a composite outcome, including any of distal DVT, proximal DVT, central venous thrombosis and pulmonary embolism.

## Summary of recommendations

### The risk of VTE in upper limb immobilisation

• There is no evidence to suggest a significant risk of VTE in ambulatory patients with isolated injury and temporary upper limb immobilisation (Grade C).

### The risk of VTE in lower limb immobilisation

• There is reasonable evidence to suggest a significant risk of VTE in ambulatory patients with isolated injury and subsequent temporary lower limb immobilisation (Grade A).

### Assessing individual risk in the ED

• No validated clinical prediction score exists to enable protocolised risk assessment in ambulatory patients with temporary limb immobilisation (Grade E).

Ambulatory patients with lower limb immobilisation and any of the following temporary risk factors should be considered to be at increased risk of venous thromboembolic disease:

• Rigid immobilisation

• Non-weight-bearing status

• Acute severe injury (dislocation, fracture or complete tendon rupture) (Grade C).

• Combination of two or more risk factors for VTE in patients with isolated limb injury increases the risk of developing subsequent VTE (Grade C).

### Who stands to benefit from thromboprophylaxis

• There is no direct evidence to suggest that ambulatory patients with lower limb injuries immobilised in splints will benefit from routine thromboprophylaxis (Grade C).

• There is evidence to support the use of thromboprophylaxis in ambulatory patients with isolated limb injury who are immobilised in below knee plaster cast (Grade A).

• There is evidence to support the use of thromboprophylaxis in ambulatory patients with isolated limb injury who are immobilised in above knee plaster cast (Grade C).

• Thromboprophylaxis should be strongly considered for ambulatory patients with lower limb injury and temporary risk (see above), in addition to any permanent additional risk factor for venous thromboembolic disease (Grade C).

### Types and duration of thromboprophylaxis

• Current evidence investigating oral anticoagulants is too limited to allow recommendation of any oral therapy as thromboprophylaxis for ambulatory patients with temporary lower limb immobilisation (Grade B).

• When indicated, the use of prophylactic low molecular weight heparin (LMWH) is effective at reducing incidence of VTE in ambulatory patients with lower limb immobilisation (Grade A).

• If commenced, prophylactic LMWH should be given for the duration of the plaster immobilisation period (Grade E).

### Risks associated with thromboprophylaxis

• The use of prophylactic LMWH is associated with low rates of heparin-induced thrombocytopenia (HIT) and major bleeding when used for thromboprophylaxis in ambulatory patients with plaster cast immobilisation (Grade A).

## Evidence for recommendations

Below are summaries of the shortcut systematic reviews used to establish the recommendations for this guideline. The three part question and search details are presented with comments and clinical bottom line.

### The risk of venous thromboembolic disease (VTE) in upper limb immobilisation

Assessing whether ambulatory patients with temporary upper limb immobilisation are at an increased risk of VTE

Three part question

In (patients with isolated upper extremity injury) does (the use of temporary immobilisation via plaster cast/sling) increase the risk of (subsequent venous thromboembolic events during short-term follow-up)?

Search strategy

Cochrane Database week ending 13 May 2011

MEDLINE and EMBASE via NHS evidence week ending 13 May 2011

[(exp IMMOBILIZATION) OR (exp CASTS, SURGICAL) OR (exp SPLINTS) OR (sling.ti,ab) OR (cast*.ti,ab) OR (immobilisation.mp) OR (plaster AND of AND paris.mp) OR (back-slab.ti/ab)] AND [(exp UPPER EXTREMITY) OR (upper AND extremity.ti,ab) OR upper AND extremity.ti,mp) OR (arm.ti,ab) OR (exp ARM INJURIES) OR (exp HAND) OR (exp HAND INJURIES) OR (exp FINGER) OR (exp FINGER INJURIES) OR (exp SHOULDER DISLOCATION) OR (exp FRACTURES, BONE)] AND [(exp VENOUS THROMBOEMBOLISM) OR (exp THROMBOEMBOLISM) OR (exp PULMONARY EMBOLISM) OR (exp DEATH, SUDDEN) OR (exp VENOUS THROMBOSIS) OR (exp THROMBOPHLEBITIS) OR (VTE.ti,ab) OR (deep AND vein AND thrombosis.mp) OR (pulmonary AND embolism.mp) OR (thrombo*.ti,ab) OR (exp RISK FACTORS) OR (*UPPER EXTREMITY DEEP VEIN THROMBOSIS/co) OR (*UPPER EXTREMITY DEEP VEIN THROMBOSIS/di)]

Search outcome

In total 104 papers were identified, of which four were felt to be relevant to the three part question. These papers are shown in table A1.

In total four studies relevant to the clinical question were identified: three retrospective cohort studies35–37 and one case–control study.38 All of these are relatively small and none were designed to directly test an association between temporary upper limb immobilisation and upper limb DVT.

### Clinical bottom line

There is currently no evidence to suggest that temporary upper limb immobilisation is associated with an increased risk of upper limb DVT.

Recommendation

• There is no evidence to suggest a significant risk of VTE in ambulatory patients with temporary upper limb immobilisation (Grade C).

### The risk of venous thromboembolic disease (VTE) in lower limb immobilisation

Assessing whether ambulatory patients with temporary lower limb immobilisation are at an increased risk of VTE

Three part question

In (non-surgical ambulatory patients with isolated lower limb injury) does (temporary immobilisation) increase the 3-month risk of (venous thromboembolic disease or sudden death)?

Search strategy

MEDLINE was searched using the OVID interface from 1948 to July Week 1 2011. EMBASE was searched using the OVID interface from 1980 to 2011 Week 27.

The Cochrane Database of Systematic Reviews was also searched using direct terminology applicable to the three part question.

(exp IMMOBILIZATION/) OR (exp CASTS, SURGICAL/) OR (exp SPLINTS/) OR (immobilisation.ti,ab) OR (immobilisation.mp) OR (plaster AND of AND paris.mp) OR (plaster AND of AND paris.ti,ab) OR (plaster AND cast.ti,ab) OR (backslab.ti,ab) OR exp Splints/] AND [(lower AND limb.ti,ab) OR (lower AND limb.mp) OR exp LEG/ OR exp Lower extremity/] AND [(exp VENOUS THROMBOEMBOLISM/) OR (exp THROMBOEMBOLISM/) OR exp Deep Vein Thrombosis/ OR (exp PULMONARY EMBOLISM/) OR (deep AND vein AND thrombosis.mp) OR (pulmonary AND embolism.mp) OR (VTE.ti,ab) OR (exp DEATH, SUDDEN)]

Search outcome

One hundred twenty-four papers were retrieved, of which four were directly relevant to the three part question33 ,34 ,36 ,38. These papers are shown in table A2.

Comment(s)

Temporary immobilisation in non-surgical isolated limb trauma within the preceding 2 months has been recently associated with 2% of all venous thromboembolic events.4 These events can be potentially fatal. Limb immobilisation has also recently been highlighted as provoking the highest risk of VTE among all causes of immobilisation.39 National guidance promotes clear advice regarding thromboprophylaxis in hospital inpatients. There is little advice regarding ambulatory patients seen in the ED who are exposed to similar risk. To address the issue properly, we must first understand the scale of the problem by identifying the incidence of disease in order to quantify risk. There are several common issues regarding the majority of studies generating data within the designated cohort. First, the use of VTE event as an outcome generates controversy: an event can range from an isolated asymptomatic distal DVT to a life-threatening PE. Some would argue that these events have profoundly differing morbidity/mortality rates and as such should not be collated as an outcome. Second, many studies group post-surgical ambulatory together with conservatively treated patients. This can distort the ED cohort and should be carefully avoided when addressing epidemiological questioning.

### Clinical bottom line

The incidence of VTE following temporary immobilisation for isolated lower limb trauma in ambulatory patients is approximately 11%. This rate can vary in different ambulatory cohorts from 5% to 30%, depending on the type of injury and immobilisation used. Although the majority of these events will be distal DVT, pulmonary emboli do occur in this cohort and contribute to total incidence.

Recommendation

• There is good evidence to suggest a significant risk of VTE in ambulatory patients with temporary lower limb immobilisation (Grade A).

### Assessing individual risk in the ED

Can individual assessment be used to predict VTE risk in the ED for patients with isolated limb trauma and temporary immobilisation?

Three part question

In (patients with lower extremity injury requiring temporary immobilisation) can (risk assessment/stratification) predict (likelihood of venous thromboembolic events within the subsequent 3 months)?

Search strategy

Cochrane Database and MEDLINE/EMBASE were searched to the week ending Friday 13 May 2011, using NHS evidence as an interface.

(exp IMMOBILIZATION/) OR (exp CASTS, SURGICAL/) OR (exp SPLINTS/) OR (immobilisation.ti,ab) OR (immobilisation.mp) OR (plaster AND of AND paris.mp) OR (plaster AND of AND paris.ti,ab) OR (plaster AND cast.ti,ab) OR (backslab.ti,ab)] AND [(lower AND limb.ti,ab) OR (lower AND limb.mp) OR exp LEG/] AND [(exp VENOUS THROMBOEMBOLISM/) OR (exp THROMBOEMBOLISM/) OR (exp PULMONARY EMBOLISM/) OR (deep AND vein AND thrombosis.mp) OR (pulmonary AND embolism.mp) OR (VTE.ti,ab) OR (exp DEATH, SUDDEN)]

Search outcome

One Cochrane review was deemed directly relevant to the three part question.9 However, this article contained no information regarding quantification of risk factors or prediction of risk for VTE. It was therefore discarded from the final analysis.

One hundred forty-eight papers were identified and reviewed by title and abstract. Only four of these papers were deemed directly relevant to the three part question.40–43 These papers are included in table A3.

No formal validated decision rule/risk assessment tool is currently available to allow stratification of thromboprophylaxis in ambulatory ED patients with temporary lower limb immobilisation. However, work has been done to identify contributory risk factors for the development of VTE during immobilisation and determine those patients most likely to benefit from thromboprophylaxis. Scoring systems based on these data and expert opinion are currently in use within the UK (Plymouth VTE trauma score), designed to approximate levels of risk and advise on thromboprophylaxis accordingly. These scores are in urgent need of validation prior to regional or national adoption. The largest study (2761 patients) addressing risk factors for the development of VTE in immobilised non-surgical isolated lower limb injuries used multivariate analysis to define predictive variables for VTE39. The authors list age >50, rigid immobilisation, non-weight-bearing status and severe injury (fracture/dislocation/complete tendon rupture) all individually resulting in an OR >1.8. Smaller previous studies support these data, noting a much lower incidence of VTE in young, low-risk, weight-bearing cohorts with predominate soft tissue injuries.8 ,41 These individual factors can thus immediately be used to highlight a cohort at increased risk for VTE. How much risk is worthy of routine prophylaxis? This is unfortunately where a dearth of high-quality evidence exists. Kujath et al42 noted a mean of two risk factors present in patients with lower limb immobilisation developing DVT and 2.7 risk factors in those developing VTE despite prophylaxis. Both figures were statistically significant compared with quantitative risk factors in those patients not developing VTE. Thus, the presence of any additional known risk factor in tandem with the above risk group implies a need for prophylaxis. In support of this approach are the data regarding the safety of prophylactic LMWH in ambulatory patients with temporary immunisation. A recent Cochrane review reported an incidence of major bleeding of <0.3%, with no cases of HIT noted in 750 patients.9 A subsequent systematic review also noted no significant risk of major or minor bleeding in over 700 patients treated with LMWH prophylaxis when compared with a similar number treated with placebo (RR 1.22, 95% CI 0.61 to 2.46, p=0.57).44 These data suggest that in the majority of ‘at-risk’ patients, the benefits of prophylaxis are indeed likely to outweigh the potential harms.

### Clinical bottom line

Ambulatory patients with temporary lower leg immobilisation who are in a rigid cast, non-weight bearing or with a severe injury should be considered as an at-risk group for VTE. If there are any other current proven VTE risk factors, including advancing age, patients should be considered as high risk.

Recommendations

• No validated clinical prediction score exists to enable protocolised risk assessment in ambulatory patients with temporary limb immobilisation (Grade E).

Ambulatory patients with lower limb immobilisation and any of the following temporary risk factors should be considered to be at increased risk of venous thromboembolic disease:

• Rigid immobilisation

• Non-weight-bearing status

• Acute severe injury (dislocation, fracture or complete tendon rupture) (Grade C).

• Combination of two or more risk factors for VTE in patients with isolated limb injury increases the risk of developing subsequent VTE (Grade C).

### Who stands to benefit from thromboprophylaxis

1. Patients temporarily immobilised in splints/wool and crepe dressings.

2. Patients temporarily immobilised in above knee plaster casts.

3. Patients temporarily immobilised in below knee plaster casts.

#### Patients temporarily immobilised in splints/wool and crepe dressings

Three part question

In (patients with knee injuries requiring immobilisation in a cricket pad splint) does (prophylactic anticoagulation with LMWH) reduce the risk of (venous thromboembolic disease over the subsequent 3 months)?

Search strategy

MEDLINE and EMBASE databases via the OVID interface the week ending 24 June 2011

MEDLINE: (exp venous thrombosis OR exp thromboembolism OR exp pulmonary embolism OR DVT.mp OR deep vein thrombosis.mp OR PE.mp OR pulmonary embolism.mp OR venous thromb$.mp) AND (exp splint OR splints.mp OR cricket pad splint.mp OR exp immobilization OR immobilization.mp) EMBASE: (exp vein thrombosis OR exp thromboembolism OR exp lung embolism OR exp venous thromboembolism OR exp deep vein thrombosis OR DVT.mp OR deep vein thrombosis.mp OR PE.mp OR pulmonary embolism.mp OR venous thromb$.mp) AND (exp splint OR splints.mp OR cricket pad splint.mp OR exp immobilization OR immobilization.mp)

Both searches were limited to human subjects only.

Search outcome

In total 401 and 1221 papers were found in the MEDLINE and EMBASE searches, respectively. None of which were felt to be relevant to the three part question.

No trials investigating the relationship between VTE and immobilising splints exist. One study by Lassen et al26 does include patients treated with ‘braces’. However, the authors do not specify the type of brace use, the numbers included are small and there is no prespecified subgroup analysis performed on this cohort.

### Clinical bottom line

There is no evidence demonstrating that ambulatory patients with lower limb injuries immobilised in splints are at an increased risk of VTE.

Recommendation

• Routine thromboprophylaxis should not be given to partially weight-bearing patients with knee injuries immobilised in splints (Grade C).

#### Patients temporarily immobilised in below knee plaster casts

A previously published shortcut review on this topic45 was updated.

Three part question

In (ambulatory patients with acute lower extremity injury requiring temporary immobilisation with below knee plaster cast) does (prophylactic dose anticoagulation with LMWH) reduce the risk of (venous thromboembolic disease within 90 days)?

Search strategy

MEDLINE and EMBASE via the Ovid interface the week ending 5 June 2011.

MEDLINE: (exp venous thrombosis OR exp thromboembolism OR exp pulmonary embolism OR DVT.mp OR deep vein thrombosis OR PE.mp OR pulmonary embolism.mp OR venous thromb$.mp) AND (exp splint OR splints.mp OR cricket pad splint.mp OR exp immobilization OR immobilisation.mp) EMBASE: (exp vein thrombosis OR exp thromboembolism OR exp lung embolism OR exp venous thrombosis OR exp deep vein thrombosis OR DVT.mp OR deep vein thrombosis.mp OR PE.mp OR pulmonary embolism.mp OR venous thromb$.mp) AND (exp splint OR splints.mp OR cricket pad splint.mp OR immobilisation.mp)

All searches were limited to human subjects only.

Search outcome

Four hundred thirty-nine and 1280 records were found in the MEDLINE and EMBASE searches, respectively. Following an initial review, 14 of these were thought to be relevant to the three part question. However, nine of these were subsequently rejected as they dealt with surgically managed patients or duplicated studies reported elsewhere. This left four RCTs and a Cochrane review. All four of the RCTs were included in the Cochrane review and therefore this was considered as the best evidence available.9 This paper is summarised in table A4.

The use of thromboprophylaxis in ambulatory patients with plaster cast immobilisation is commonplace in most European countries. Current UK use is minimal, likely as a result of recent national guidance failing to give clear recommendations. Since the original BET on this topic in 2007,45 there have been three systematic reviews published.9 ,44 ,46 Two of these include postoperative orthopaedic surgical ambulatory patients within the analysis44 ,46 and are thus limited in their applicability to an emergency medicine cohort. The Cochrane review cited above, however, does subgroup non-surgical patients to address specific risk within the conservatively managed outpatient group. The evidence presented suggests that the use of thromboprophylaxis can significantly reduce the chance of a venous thromboembolic (VTE) event in patients with a below knee plaster cast and those conservatively treated. ARR varies between 6.8% and 7.1% in these groups. These data would suggest a NNT of 14 to prevent one event. Furthermore it is worth noting that all included studies within the meta-analysis exclude patient groups considered to be high risk for developing VTE; the rate of DVTs seen will likely underestimate that found in an undifferentiated ED population. However, the clinical significance of these results is uncertain. Despite the high rate of DVTs seen the majority (66–100%) were asymptomatic and would therefore be unlikely to be detected in normal clinical practice. In addition, pulmonary embolism was only seen in 0.3% cases and no deaths occurred within the untreated cohort. A high prevalence of distal DVT serving as a positive outcome also generates debate regarding routine use; the rate of propagation, embolisation and post-thrombotic syndrome seen to follow distal DVT remains poorly quantified.31 Although rates of HIT and major bleeding were low overall (<0.3%), concerns remain regarding the wider impact of generalised use. It is necessary to balance any benefit gained against the potential risk of increased bleeding with the use of LMWH. Therefore individual stratification of both VTE and bleeding risk would seem prudent prior to prophylaxis.

### Clinical bottom line

The use of LMWH thromboprophylaxis is effective at reducing the incidence of VTE in ambulatory patients with below knee plaster casts. For every 14 patients treated, one episode of VTE will be prevented. The vast majority of VTE episodes will be asymptomatic DVT. The risk of PE or sudden death without prophylaxis is low.

Recommendations

• There is evidence to support the use of thromboprophylaxis in ambulatory patients with isolated limb injury who are immobilised in below knee plaster cast (Grade A).

#### Patients temporarily immobilised in above knee plaster casts

Three part question

In (patients with lower extremity injury requiring temporary immobilisation with above knee plaster of paris) does (prophylactic anticoagulation with LMWH) reduce the risk of (venous thromboembolic disease within the next 3 months)?

Search strategy

MEDLINE and EMBASE via the OVID interface the week ending 8 July 2011. The Cochrane Database was also searched using direct terminology.

MEDLINE: (exp venous thrombosis OR exp thromboembolism OR exp pulmonary embolism OR DVT.mp OR depp vein thrombosis.mp OR PE.mp OR pulmonary embolism.mp OR venous thromb.mp OR exp immobilization OR immobilization.mp)

EMBASE: (exp vein thrombosis OR exp thromboembolism OR exp lung embolism OR exp venous thromboembolism OR exp deep vein thrombosis OR DVT.mp OR deep vein thrombosis.mp OR PE.mp OR pulmonary embolism.mp OR venous thromb$.mp) AND (exp splint OR splints.mp OR cricket pad splint.mp OR immobilisation.mp) All searches were limited to human studies only. Search outcome Four hundred forty and 1280 records were found in the MEDLINE and EMBASE searches, respectively. Following an initial abstract review, 14 of these were deemed relevant. However, 13 were subsequently rejected as they either duplicated data presented elsewhere (nine) or they did not include patients treated in above knee casts (four). The remaining paper is shown in table A5. Comments The evidence for use of thromboprophylaxis in ambulatory patients immobilised with above knee casts is limited and comes from a single RCT.25 Unfortunately, these patients were not part of a predetermined subgroup and therefore the numbers included are small and no statistical analysis has been performed. However, the data suggest an ARR in the order of 8% associated with the use of thromboprophylaxis, which would give an NNT of 12. These results are comparable with the effect of thromboprophylaxis seen in patients treated with below knee casts.9 Given that an above knee cast provides a greater degree of immobility7 it would be logical to assume that the risk of VTE is at best the same with the two different types of immobilisation. It should also be noted that a large proportion of above knee casts are also non-weight bearing, which has itself been demonstrated to be an independent risk factor for the development of VTE in ambulatory patients with lower limb immobilisation.43 ### Clinical bottom line Although the evidence examining the use of thromboprophylaxis in this specific subgroup is limited, that which does exist suggests the use of thromboprophylaxis to be effective at reducing the incidence of VTE. Recommendation • Ambulatory patients immobilised in above knee plaster casts are at increased risk of VTE and thromboprophylaxis should be considered (Grade C). ### Thromboprophylaxis 1. Type 2. Duration #### Can we use oral thromboprophylaxis for temporary immobilisation in ambulatory patients with isolated limb injury Three part question In (ambulatory patients with temporary immobilisation of the lower limb following isolated trauma) does the use of (aspirin, a factor Xa inhibitor or any other method of oral thromboprophylaxis) prevent (venous thromboembolic disease over the subsequent 3 months)? Search strategy MEDLINE was searched using the OVID interface from 1948 to July Week 1 2011. EMBASE was searched using the OVID interface from 1980 to 2011 Week 27. The Cochrane Database of Systematic Reviews was also searched using direct terms. [(lower limb adj (immobiliz)).mp. OR Immobilization/ OR (Immobiliz) OR exp Casts, Surgical/ OR plaster cast.mp OR plaster of paris.mp OR exp Splints/] AND [exp Lower Extremity/ OR Lower Extremity.tw OR exp LEG/] AND [Aspirin/ OR aspirin.mp. OR Factor Xa/ OR factor xa inhibitor.mp] AND [exp Thromboembolism/ OR exp Venous Thrombosis OR exp Deep Vein Thrombosis OR thromboembolism.mp OR thrombo$.mp OR exp Sudden death/ OR pulmonary embolism.mp]

Search outcome

Thirty-seven papers were found, of which only one addressed the three part question.47 This paper is shown in table A6.

Comment(s)

Multiple prospective RCTs have been conducted investigating the use of LMWH as thromboprophylaxis for transiently immobilised patients with limb injury. Unfortunately, little evidence investigates the efficacy of other forms of prophylaxis. The increasing emergence of studies supporting the prophylactic use of oral factor Xa inhibitors in orthopaedic surgery48 ,49 will no doubt lead to wider use of these drugs within thromboembolism research. As yet, they have not been trialled in immobilised ambulatory patients. Only one trial has assessed the use of aspirin in this situation. This was a pilot study in a German Journal with several methodological concerns.

### Clinical bottom line

There is currently little evidence to support the use of oral thromboprophylaxis for ambulatory patients with immobilisation of the lower limb. While pilot studies would suggest aspirin may have a similar efficacy to LMWH, further trials are needed. If required, prophylaxis should be currently achieved with LMWH, for which a large evidence base exists.

Recommendation

Current evidence investigating oral anticoagulants is too limited to allow recommendation of any oral therapy as thromboprophylaxis for ambulatory patients with temporary lower limb immobilisation (Grade B).

#### If the decision is taken to prescribe thromboprophylaxis for immobilised ambulatory limb trauma, what duration of prophylaxis is indicated?

Three part question

In (ambulatory patients with temporary lower limb immobilisation) what is (the optimum duration of thromboprophylaxis needed) to prevent (a venous thromboembolic event)?

Search strategy

MEDLINE and EMBASE databases were searched via the OVID interface the week ending 8 April 2012 using the following strategies.

MEDLINE: (exp venous thromboembolism OR exp pulmonary embolism OR exp thromboembolism OR exp venous thrombosis OR venous thromboembolism.mp OR deep vein thrombosis.mp OR DVT.mp OR pulmonary embolism.mp OR PE.mp OR venous thromb$.mp) AND (Casts, surgical OR plaster cast$.mp OR plaster of paris.mp OR exp immobilization OR immobilisation.mp) AND (exp heparin OR exp anticoagulants OR exp heparin, low-molecular-weight OR low molecular weight heparin.mp OR thromboprophylaxis.mp)

EMBASE: (exp vein thrombosis OR exp thromboembolism OR exp lung embolism OR exp venous thromboembolism OR exp Deep vein thrombosis OR deep vein thrombosis.mp OR DVT.mp OR pulmonary embolism.mp OR venous thromb$.mp) AND (exp plaster cast OR plaster cast.mp OR exp immobilization OR immobilisation.mp) AND (exp heparin OR exp low molecular weight heparin OR exp anticoagulant agent OR thromboprophylaxis.mp) Both searches were limited to human studies only. Search outcome The above searches generated 212 and 826 citations, respectively. None of these were found to be directly relevant to the three part question. Comment(s) There have been no studies examining the optimum duration of thromboprophylaxis needed in ambulatory patients with plaster cast immobilisation. The studies which provide evidence for the use of thromboprophylaxis in this patient cohort universally gave LMWH for the duration of the plaster cast and in the absence of any good evidence to the contrary it would seem prudent to recommend the same.25 ,26 ,42 ,50 A recommendation that is in keeping with the recent NICE guidance and the conclusions from the recent Cochrane review, both of which advise clinicians to offer LMWH for the duration of the plaster cast if indicated.1 ,9 However, the risk of having a VTE event is unlikely to remain the same throughout the period of immobilisation. The highest risk of developing a venous thrombosis is maximal during the first 10 days post-injury and the risk is likely to lessen as patients are allowed to weight bear towards the end of their treatment. This could be used as an argument for limiting the use of thromboprophylaxis to the period of highest risk, an approach that is in keeping with some17 ,41 but not all46 ,51 clinicians who commonly use prophylaxis in this patient cohort. ### Clinical bottom line There is no good evidence regarding the duration of thromboprophylaxis needed in ambulatory patients with temporary lower limb immobilisation. Therefore, it is the recommendation of the authors that thromboprophylaxis should be continued for the duration of the plaster cast, in line with the recent NICE guidance. Recommendation • If commenced, prophylactic LMWH should be given for the duration of the plaster immobilisation period (Grade E). ### Risks associated with thromboprophylaxis What are the risks associated with prescription of thromboprophylactic doses of LMWH over a several-week period, with specific reference to HIT/major bleeding. ### Three part question In (patients with lower extremity injury requiring temporary immobilisation) does (prophylactic anticoagulation with LMWH) increase the incidence of (fatal, major or minor bleeding episodes)? Search strategy MEDLINE and EMBASE databases were searched using the OVID interface the week ending 8th July 2011 using the following strategies. MEDLNE: (exp Casts, Surgical OR plaster cast) AND (exp Heparin, low-molecular-weight OR exp enoxaparin OR exp Dalteparin OR LMWH.mp OR low molecular weight heparin.mp OR clexane.mp OR dalteparin.mp OR fragmin.mp OR tinzaparin.mp OR enoxaparin.mp) EMBASE:(exp plaster cast OR plaster cast$.mp OR exp immobilization OR immobilisation.mp) AND (exp low molecular weight heparin OR low molecular weight heparin.mp OR LMWH.mp OR exp enoxaparin OR enoxaparin.mp OR clexane.mp OR exp dalteparin OR dalteparin.mp OR fragmin. mp OR exp tinzaparin OR tinzaparin.mp)

All searches were limited to human studies only.

Search outcome

One hundred one and 460 records were found, respectively. Four unique RCTs examining the study population were found, along with one prospective observational review and two meta-analyses. The two meta-analyses9 ,44 include the same six papers, four of which are the RCTs identified. Therefore the Cochrane review, along with the prospective observational study,52 is presented below as it gives the most complete data regarding adverse events. This paper is shown in table A7.

Comment(s)

The use of prophylactic LMWH, for the prevention of VTE, is widely employed in both the inpatient and outpatient settings. As with all anticoagulant therapies, its use is associated with an increased risk of bleeding and additionally a theoretical risk of HIT is present, although this is less common with low molecular weight heparin than with unfractionated heparin. The evidence presented demonstrates the use of LMWH to be safe in the target population: a risk of major bleeding of 0.11–0.27% is reported,9 ,44 ,52 with a number needed to harm of 769. When this is compared with the estimated number needed to treat of 14 to prevent one VTE event in the same cohort, it follows that the benefits of LMWH prophylaxis outweigh the risks.9 In addition, no deaths from bleeding were reported in either of the presented studies as well as minimal rates of minor bleeding (1.51–2.7%) and HIT (0–0.17%).9 ,52 Furthermore it is worth noting that LMWH thromboprophylaxis has been proven to be equally safe in the elderly (a subgroup which can cause particular concern) with studies demonstrating rates of major bleeding and HIT of 0.4–0.49% and 0.54–1.4%, respectively,53 ,54 although it is important to note that these studies have been carried out in medical patients and not the target cohort. As persuasive as these figures regarding the benefits and risks of LMWH thromboprophylaxis are, it is important to consider each patient on an individual basis and it is worth remembering that high-risk patients, both for bleeding and VTE risk, have been excluded from the studies likely resulting in an exaggeration of the overall benefit and risk ratio.

## Evidence-based flowchart

### Clinical bottom line

LMWH is safe to use as thromboprophylaxis in patients with lower limb plaster casts. Associated rates of major bleeding and thrombocytopenia are low, less than 0.2% in the related cohort.

Recommendations

The use of prophylactic LMWH is associated with low rates of HIT and major bleeding when used for thromboprophylaxis in ambulatory patients with plaster cast immobilisation (Grade A).

PDI/01: SUITABILITY FOR PROTOCOL-DRIVEN THERAPY

CDU/01: DOES A TRANSIENT RISK OF VTE EXIST (ANY YES)

CDU/02: DOES ANY PERMANENT RISK OF VTE EXIST (ANY YES)

CDU/03: ANY RELATIVE CONTRAINDICATION TO LMWH (ANY YES)

REF/01: THROMBOPROPHYLAXIS IS ADVISED (ALL YES)

## Appendix

Table A1

Risk in upper limb immobilisation

Table A2

Risk in lower limb immobilisation

Table A3

Individualised risk assessment

Table A4

Below knee immobilisation

Table A5

Above knee immobilisation

Table A6

Type of thromboprophylaxis

Table A7

Risks of thromboprophylaxis

View Abstract

## Footnotes

• Competing interests None.

• Provenance and peer review Commissioned; internally peer reviewed.

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