Air travel and prevention of venous thromboembolism by medication

Evidence Summaries

Level of Evidence = D
There is insufficient evidence on the effectiveness of medication use for the prevention of travel-related venous thromboembolism. Aspirin is probably not effective and for low-molecular-weight-heparin (LMWH) there might possibly be a trend favoring limited effect.

A systematic review 1 included 25 studies (6 case-control studies, 10 cohort studies, and 9 randomized controlled trials) in order to estimate the risk of travel-related venous thromboembolism (VTE), and evaluate the efficacy of preventive treatments. Clinical VTE meaning pulmonary embolism (PE) or deep venous thrombosis (DVT) after prolonged travel is rare (27 symptomatic VTEs per million flights diagnosed through usual clinical care, 0.05% symptomatic DVTs diagnosed through screening ultrasounds), but asymptomatic thrombi of uncertain clinical significance are more common (ranging from 0% to 12%). Multivariate logistic regression analysis showed that mean duration of air travel >8 hours and high clinical risk of VTE ( 1 of previous DVT, prothrombotic blood disorder, body weight >90 kg, limited mobility, cancer, or large varicose veins) increased risk of air-travel-related VTE.

In randomized controlled trials, graduated compression stockings prevented travel-related VTE (P < 0.05 in 4 of 6 studies).

Only 1 study 2 evaluated LMWH (enoxaparin 1 mg/kg injected 2–4 h before flight) and found a trend favoring effective DVT prevention that did not reach statistical significance. The same study found no effect from aspirin (400 mg ASA daily for 3 days, starting 12 h before flight). In control group (n=82) 4.8% of limbs suffered a thrombotic event, in aspirin group (n=84) 3.6% of limbs had a thrombotic event, and in LMWH group (n=82) only 0.6% of limbs had a thrombotic event (p<0.002 in comparison with the other two groups).

No studies tested warfarin or unfractionated heparin. Two studies evaluated preparations containing pycnogenol, an extract of pine bark with antioxidant and possible antithrombotic effects with 1 study reporting fewer DVTs among treated passengers.

Comment: The quality of evidence is downgraded by study quality (most studies enrolled volunteers who tend to be healthier than nonvolunteers), by inconsistency (heterogeneity in interventions and outcomes) and by imprecise results (limited study size for each comparison).


1. Philbrick JT, Shumate R, Siadaty MS et al. Air travel and venous thromboembolism: a systematic review. J Gen Intern Med 2007;22(1):107-14.  [PMID:17351849]
2. Cesarone MR, Belcaro G, Nicolaides AN et al. Venous thrombosis from air travel: the LONFLIT3 study--prevention with aspirin vs low-molecular-weight heparin (LMWH) in high-risk subjects: a randomized trial. Angiology 2002;53(1):1-6.  [PMID:11863301]
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