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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 three months]

Clinical Scenario

A patient presents to the Emergency Department with isolated Weber C ankle fracture. He is placed in a non weight bearing plaster cast. He has a previous history of DVT and is an active smoker. You are concerned about the risk of recurrent DVT and discuss the potential benefits of thromboprophylaxis with him. He is keen, but unfortunately claims to be needle phobic and is reluctant to take daily subcutaneous LMWH.
You wonder if there is any evidence to support any type of oral thromboprophylaxis in this situation.

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$ or immobilis$)).mp. OR Immobilization/ OR (Immobiliz$ or Immobilis$) OR exp Casts, Surgical/ OR plaster cast.mp OR plaster of paris.mp OR exp Splints/] AND [exp Lower Extremity/ OR Lower Extremity.tw OR exp LEG/] AND [Aspirin/ OR aspirin.mp. OR Factor Xa/ OR factor xa inhibitor.mp] AND [exp Thromboembolism/ OR exp Venous Thrombosis OR exp Deep Vein Thrombosis OR thromboembolism.mp OR thrombo$.mp OR exp Sudden death/ OR pulmonary embolism.mp]

Search Outcome

37 papers were found, of which only one addressed the three part question. This paper is summarised below:

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Gehling et al. January 1998 Germany	287 patients presenting with lower extremity injuries, who required immobilising bandages or casts.	Randomized controlled trial in which thromboprophylaxis was administered in the form of a subcutaneous injection of divarin 1750 once daily in 143 patients and with Aspirin 2 x 500 mg orally in 144 patients. A clinical examination and colour-coded duplex sonography were performed after removal of the cast for detection of lower extremity venous thrombosis. A phlebography was performed for confirmation when thrombosis was suspected.	Incidence of DVT in group recieving prophylactic LMWH	9/143 (6.3%)	Heterogenous cohort consisting of inpatients, outpatients and surgical patients. No distinction between symptomatic/asymptomatic disease
			Incidence of DVT in group recieving prophylactic Aspirin	7/144 (4.8%)

Comment(s)

Multiple prospective randomised controlled trials 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 surgery [1,2] 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.

Level of Evidence

Level 2 - Studies considered were neither 1 or 3.

References

1. Gehling H, Giannadakis K, Lefering R, Hessmann M, Achenbach S, Gotzen L Prospective randomized pilot study of ambulatory prevention of thromboembolism. 2 times 500 mg aspirin (ASS) vs. clivarin 1750 (NMH). Unfallchirurg. 1998 Jan;101(1):42-9.
2. Lassen M, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, Misselwitz F and Turpie A for the RECORD3 Investigators Rivaroxaban versus Enoxaparin for Thromboprophylaxis after Total Knee Arthroplasty The New England Journal of Medicine 2008;358(26):2776-2786
3. Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D and Ramirez LM for the ADVANCE-3 Investigators Apixaban versus Enoxaparin for Thromboprophylaxis after Hip Replacement The New England Journal of Medicine 2010;363(26):2487-2498