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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]?

Clinical Scenario

A 23-year-old female presents to your department following a fall and is diagnosed with a Weber B ankle fracture by one of your junior colleagues. They arrange plaster immobilisation and fracture clinic follow-up for 1 week later. Before discharge they approach you and raise the question of thromboprophylaxis. The patient is a smoker and on the combined oral contraceptive pill, but otherwise has no clear risk factors for venous thromboembolism (VTE).

You wonder if there is any means of predicting the patient's risk for subsequent VTE in order to help make an evidence based decision regarding thromboprophylaxis.

Search Strategy

Cochrane database and MEDLINE/EMBASE were searched to the week ending Friday 13th 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

1 Cochrane review was deemed directly relevant to the three part question. 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.
148 papers were identified and reviewed by title and abstract. Only 4 of these papers were deemed directly relevant to the three part question. These papers are included in the table of evidence below:

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Riou et al 2007 France	3698 adult patients presenting to the ED with isolated non surgical lower limb injury below the knee. 2761 (75%) completed follow up and underwent full leg compression ultrasound of the affected limb.	Prospective multicentre observational cohort (level of evidence 2b)	Incidence of VTE after removal of immobilisation	6.4% (95% CI 5.5 to 7.4%)	ED physicians were left to decide on type of VTE prophylaxis: over 60% patients received some form of pharmacological prophylaxis. This sample is thus not truly reflective of an untreated Emergency Department population. Only 75% ultrasound follow up rate (2761 patients).
			Predictive Variables of VTE development after multivariate analysis	Age >50 (OR 3.14, p<0.0001), Rigid immobilisation (OR 2.70, p<0.0001), Non weight bearing status (OR 4.11, P=0.0015) and Severe injury (OR 1.88, p=0.0002)
Eisele et al 1998 Germany	731 outpatients with recent injury or surgery of the leg/pelvis. All patients underwent pre and post ultrasonic investigation for DVT in the lower extremeties.	Prospective interventional cohort. A subjective scoring system to ascertain risk of VTE within the cohort was created based on previous research and expert opinion. This scoring system was applied to each patient with a binary risk outcome and prescription of prophylaxis in tandem with a 'high risk' score. (level of evidence 4)	Incidence of VTE in patients deemed to be at 'high risk' of development.	4%	Scoring system was not independently derived from original research (no mention of risk stratification/risk ratios for independent variables/derivation set). All patients deemed to be at high risk were treated with LMWH/UFH. No attempt at external validation. No confidence intervals given. No sub group analysis to identify risk factors for those developing DVT in the conservatively treated cohort.
			Incidence of VTE in patients deemed to be at 'low risk' of development.	0.6%
Kujath et al 1993 Germany	253 ambulatory outpatients with lower limb injuries treated with immobilisation by plaster cast	Prospective randomised controlled trial. 126 patients randomised to LMWH and 127 receiving no thromboembolic prophylaxis. Data on risk factors collated and analysed to determine quantfiable risk in relation to development of thrombosis. (level of evidence 2b)	Incidence of VTE in therapeutic arm	4.8%	No multivariate analysis performed on individual risk factors: the presence of each risk factor was compared in patients with and without thrombosis to evaluate statistical significance. Included patients undergoing surgical intervention at a later date. 5 patients had DVT on ultrasound with failed phlebographic confirmation.
			Incidence of VTE in conservative arm	16.5%
			Number of average risk factors present in patients developing DVT	1.96
Giannadakis et al, 2000, Germany	178 ambulatory patients immobilised in plaster casts for lower limb injuries deemed to be at low risk of thromboembolic disease, and therefore prescribed no pharmacological prophylaxis. Most of these patients had a fibular ligament injury (144), with the remaining 34 patients having metatarsal fractures (16), ankle fractures (11), calcaneal fractures (4) and talar fractures (3).	Prospective observational cohort. All patients were clinically examined and underwent colour-coded duplex sonography for detection of DVT after removal of the cast at the end of the immobilisation period. Confirmation of DVT was performed by contrast venography when suspected on ultrasound (level 2b)	Incidence of lower limb DVT within the cohort	1.1% (95% CI 0% to 4.4%)	Very low incidence of fractures within the cohort and no subgroup analysis. ‘Low risk’ cohort defined by local guidance rather than validated decision tool. Investigation of pulmonary VTE based on clinical suspicion only. Limited data on method of duplex assessment including objective criteria for diagnosis of calf thrombi.
			Incidence of clinically suspected pulmonary VTE within the cohort	0%

Comment(s)

No formal validated decision rule/risk assessment tool is currently available to allow stratification of thromboprophylaxis in ambulatory emergency department 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 VTE. 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. 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 al noted a mean of two risk factors present in patients with lower limb immobilisation developing deep vein thrombosis and 2.7 risk factors in those developing VTE despite prophylaxis. Both figures were statistically significant compared to 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 imply a need for prophylaxis. In support of this approach are the data regarding the safety of prophylactic low molecular weight heparin (LMWH) in ambulatory patients with temporary immunisation. A recent Cochrane Review reported an incidence of major bleeding of <0.3%, with no cases of heparin induced thrombocytopenia noted in 750 patients. A subsequent systematic review also noted no significant risk of major or minor bleeding in over 700 patients treated with LMWH prophylaxis, when compared to a similar number treated with placebo (RR 1.22, 95% CI 0.61 to 2.46, p=0.57). These data suggest that in the majority of ‘at risk’ patients, the benefits of prophylaxis are indeed likely to outweigh the potential harms.

Editor Comment

DVT, deep vein thrombosis; ED, emergency department; LMWH, low molecular weight heparin; UFH, unfractionated heparin; VTE, venous thromboembolism.

Clinical Bottom Line

Ambulatory patients with temporary lower leg immobilisation who are over 50, 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, patients should be considered as high risk.

Level of Evidence

Level 2 - Studies considered were neither 1 or 3.

References

1. Riou B, Rothmann C, Lecoules N, Bouvat E, Bosson J-L, Ravaud P, Samama CM and Hamadouche M Incidence and risk factors for venous thromboembolism in patients with nonsurgical isolated lower limb injuries American Journal of Emergency Medicine 2007;25:502-508
2. Eisele R, Hoellen I and Kinzi L. Drug prophylaxis of deep vein thrombosis in traumatology: Is there a benefit of a score in outpatients? Lagenbeck's Archives of Surgery 1998;383:481-484
3. Kujath P, Spannagel U and Habscheid W. Incidence and prophylaxis of deep vein thrombosis in outpatients with injury of the lower limb Haemostasis 1993;23(Suppl 1):20-26
4. Giannadakis K, Gehling H, Sitter H, et al. Is a general pharmacologic thromboembolism prophylaxis necessary in ambulatory treatment by plaster cast immobilisation in lower limb injuries? Der Unfallchirurg 2000;103:475–8.