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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]

Clinical Scenario

A 34 year old female presents to the emergency department following an inversion injury to her ankle. An x-ray reveals a fracture, suitable for conservative management in a below-knee plaster cast. You are aware of an ongoing medico-legal case at your trust regarding a patient recently admitted with a pulmonary embolism, which was attributed to plaster cast immobilisation.

You wonder if thromboembolic prophylaxis will significantly reduce the risk of subsequent VTE in your patient.

Search Strategy

MEDLINE and EMBASE databases were searched, using the Ovid interface, the week ending the 25th February 2012

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$.mp) AND (exp casts surgical OR plaster cast$.mp OR exp immobilization OR immobilisation.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$.mp) AND (exp plaster cast OR exp immobilization OR plaster cast$.mp OR immobilisation.mp)

All searches were limited to human studies only.

Search Outcome

490 and 1700 records were found in the MEDLINE and EMBASE searches respectively. Following an initial abstract review 16 of these were deemed to be relevant to the 3 part question. However, 11 of these were subsequently rejected as they dealt with surgically managed patients or duplicated studies reported elsewhere. This resulted in 4 prospective randomised trials and 1 Cochrane review. On inspection, all four RCT’s were included in the Cochrane systematic review. This review is presented below as the highest level of evidence:

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Testroote M et al 2009 Netherlands	Adult outpatients with lower-limb injuries treated in a brace or plaster cast.	Systematic review and meta-analysis of 6 RCTS (1490 patients). Subgroup analyses included 788 patients managed non-surgically and 894 patients treated in a below-knee cast. (level of evidence 1-)	Overall incidence of DVT	Placebo group: 18.1%, LMWH group: 10% OR 0.49 (95% CI 0.34 - 0.72)	Statistical and clinical heterogeneity. The number of patients in the included studies are small. The assessment of patients in below-knee plaster casts includes patients managed surgically.
			Incidence of DVT in conservatively managed patients	Placebo group: 11.3%, LMWH group: 4.2% OR 0.35 (95% CI 0.19 - 0.62)
			Incidence of DVT in patients in a below-knee POP	Placebo group18.6%, LMWH group: 11.8% OR 0.54 (95% CI 0.37 - 0.8)

Comment(s)

The use of thromboprophylaxis in ambulatory patients with plaster cast immobilisation, is commonplace in most European countries. Current UK use is minimal, probably as a result of recent national guidance failing to give clear recommendations. Since the original BET on this topic in 2007 (Brown), three systematic reviews have been published (Testroote, Metz, Ettema). Two of these include postoperative orthopaedic surgical ambulatory patients within the analysis (Metz, Ettema) 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 VTE in patients with a below-knee plaster cast and those conservatively treated. The adjusted relative risk varies between 6.8% and 7.1% in these groups. These data would suggest a number needed to treat 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 deep vein thrombosis (DVT) seen will probably underestimate that found in an undifferentiated emergency department population. However, the clinical significance of these results is uncertain. Despite the high rate of DVT 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% of 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. Although rates of heparin-induced thrombocytopaenia 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 before prophylaxis.

Editor Comment

This report is an update to BET 451 http://www.bestbets.org/bets/bet.php?id=451

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, 1 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

References

1. Testroote M, Stigter WAH, de Visser DC, et al. Low Molecular Weight Heparin for Prevention of Venous Thromboembolism in Patients with Lower-Leg Immobilisation (Review) The Cochrane Database of Systematic Reviews 2009; (4): CD006681.
2. Brown E, Bleetman A Prophylaxis of Venous Thromboembolism in Patients with Lower Limb Plaster Cast Immobilisation EMJ 2007;24:495-496
3. Metz R, Verleisdonk E, van der Heijden G, et al. Insufficient Evidence for Routine Use of Thromboprophylaxis in Ambulatory Patients with an Isolated Lower Leg Injury Requiring Immobilization: Results of a Meta-Analysis Eur J Trauma Emerg Surg 2009;35:169–75
4. Ettema HB, Kollen BJ, Verheyen CC, et al. Prevention of Venous Thromboembolism in Patients with Immobilization of the Lower Extremities: A Meta-Analysis of Randomized Controlled Trials J Thromb Haemost 2008; 6: 1093–8.
5. Brown E, Bleetman A. Prophylaxis of venous thromboembolism in patients with lower limb plaster cast immobilisation [Online] at http://www.bestbets.org/bets/bet.php?id=455 2007