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Three Part Question

In [patients with leg injuries requiring lower limb plaster cast immobilisation] is [low molecular weight heparin] necessary to [prevent venous thromboembolism]?

Clinical Scenario

A 48 year old man attends the emergency department with pain and swelling in his right calf after a game of squash. Clinical examination supported by ultrasound identifies a partial rupture of the Achilles tendon. You decide to treat him with an equinus plaster cast and arrange follow up. You wonder whether you should prescribe low-molecular weight heparin for venous thromboembolism prophylaxis for the duration of immobilisation in the cast.

Search Strategy

Medline 1950 to week 4 August 2006 using the Dialog Datastar interface.
EMBASE using the Dialog Datastar interface 1950 to week 4 August 2006
Cochrane Issue 3, 2006.
Medline:((casts) OR (casts-surgical#.de.) OR (plaster ADJ cast)) AND ((leg) OR (leg#.w..de.) OR (lower ADJ limb) OR (lower-extremity#.de.)) AND ((low ADJ molecular ADJ weight ADJ heparin) OR (heparin-low-molecular-weight#.de.) OR (lmw ADJ heparin) OR (lmwh) OR (thromboprophylaxis)) AND ((deep ADJ vein ADJ thrombosis) OR (venousthrombosis#. de.) OR (venous ADJ thromboembolism) OR (thromboembolism#.w..de.) OR (pulmonary ADJ embolism) OR (pulmonaryembolism#.
de.)) limited to human and English
Embase:((cast) OR (plaster ADJ cast) OR (plaster-cast#.de.)) AND ((leg) OR (leg#.w..de.) OR (lower ADJ limb) OR (lower ADJ extremity)) AND ((low ADJ molecular ADJ weight ADJ heparin) OR (low-molecular-weight-heparin#.de.) OR (lmw ADJ heparin) OR (lmwh) OR (thromboprophylaxis)) AND ((deep ADJ vein ADJ thrombosis) OR (deep-veinthrombosis#.de.) OR (venous ADJ thromboembolism) OR (venousthromboembolism#.de.) OR (pulmonary ADJ embolism) OR (lung-embolism#.de.)). Limted to human and English
Cochrane:('cast' and 'venous thrombosis' OR 'venous thromboembolism' OR 'deep vein thrombosis' OR 'pulmonary embolism')

Search Outcome

In total 17 papers were found of which four were relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Kock et al, 1995, Germany	239 patients with leg injuries requiring conservative treatment in plaster cast or cylinder cast as outpatients. 176 received 32mg s.c. mono-embolex until cast removal. 163 received no treatment	Prospective, randomised, single centre, open, control trial.	Deep vein thrombosis found at cast removal by clinical examination, leg measurement ultrasound and duplex scanning, with phlebography to confirm positive findings	There were no DVTs in the prophylaxis group (0%), whereas 7/163 (4.3%) in the no treatment group had DVT. This reached statistical significance (p<0.006)	No placebo No assessor blinding Method of randomisation not specified
Lassen et al, 2002, Denmark	371 patients with leg fracture or Achilles tendon rupture requiring at least five weeks of immobilisation in plaster cast or brace. 217 received reviparin s.c. 1750 units daily and 223 received placebo.	Prospective, randomised, doubleblind, placebo controlled multicentre (six hospitals) trial.	Deep vein thrombosis found by ascending venography within one week of cast removal. Ventilation perfusion scanning performed in those showing clinical signs of pulmonary embolus	DVT diagnosed in 17 (9%) in the reviparin group 35; (19%) in the placebo group: the difference was statistically significant (p<0.05). 2 patients developed confirmed PE- both in the placebo group.	Some patients received surgical intervention;results for these patients not distinguishable from those receiving conservative treatment. No detail of placebo content.
Jorgensen et al, 2002, Denmark	205 patients with planned plaster cast on lower extremity for 3 weeks. 99 received 3,500 IU tinzaparin s.c. daily; 106 received no treatment	Prospective, randomised, assessor-blinded, multicentre (3 centres) controlled trial	DVT on ascending venography on day of cast removal	DVT found in 10/99 (10%) of the treatment group and 18/106 (17%) in the control group. These results were not statistically significant (p=0.15)	Not statistically significant result- possibly attributable to either high drop out rate(95 of original 300) or low dose of LMWH. No placebo control
Kujath et al, 1993, Germany	253 outpatients with lower limb injury treated conservatively in lower limb plaster cast. 126 allocated to receive 36mg s.c. fraxiparin daily, 127 received no treatment	Prospective, randomised, open single centre, controlled trial	Deep vein thrombosis at cast removal by USS. Positive or doubtful findings confirmed by venography.	The group had no prophylaxis had 21 DVT (16.5%) compared to 6 in the prophylaxis group (4.8%) The difference was statistically significant (p<0.01)	No placebo. No assessor blinding. Adverse effects of treatment not reported.

Comment(s)

Patients receiving subcutaneous injections on a daily basis need either to be trained to self-inject, to return to a health professional each day, or else remain an inpatient. The vast majority of patients in these studies were outpatients and coped well with self-injecting. Further research is needed to assess the cost-effectiveness of the increased resources needed to offer this treatment. No two studies used the same low-molecularweight heparin; the appropriate dose of any particular LMWH treatment has yet to be determined. There appears to be no significant increased risk of bleeding complications or other adverse reactions from LMWH for VTE prophylaxis.

Editor Comment

Update to this report is BET 2238 at http://www.bestbets.org/bets/bet.php?id=2238

Clinical Bottom Line

In patients requiring lower limb plaster cast immobilisation for injury (fractures and soft tissue), there is evidence supporting the use of LMWH as thromboprophylaxis for venous thromboembolism.

References

1. Kock HJ, Schmit-Neuerburg KP, Hanke J, et al. Thromboprophylaxis with lowmolecular-weight heparin in outpatients with plaster-cast immobilisation of the leg. Lancet 1995;346:459-61.
2. Lassen MR, Borris LC, Nakov RL. Use of the low-molecular-weight heparin reviparin to prevent deep-vein thrombosis after leg injury requiring immobilisation. N Engl J Med 2002;347(10):726-30.
3. Jorgensen PS, Warming T, Hansen K, et al. Low molecular weigh heparin (Innohep) as thromboprophylaxis in outpatients with a plaster cast: a venographic controlled study. Thromb res 2002;105(6):477-80.
4. Kujath P, Spannagel U, Habscheid W. Incidence and prophylaxis of deep venous thrombosis in outpatients with injury of the lower limb. Haemostasis 1993;23(Suppl1):20-6.
5. Roberts C, Horner D. Thromboprophylaxis significantly reduces venous thromboembolism rate in ambulatory patients immobilised in below knee plaster cast. [Online] at Bestbets.org/bets/bet.php?id=2238 2011