Erik Hansen, David Nazarian.
Response/Recommendation: It is well established that travel on airplanes, especially ‘long-haul flights’, is a major risk factor for development of venous thromboembolism (VTE). Individuals with preexisting risk factors for VTE appear to be at the greatest risk. There is a paucity of literature examining the influence of long-distance travel prior to surgery on the risk of postoperative VTE. Similarly, while it is commonly accepted that airplane travel in the acute postoperative period should be avoided due to an increased risk of VTE, there is limited evidence supporting this notion. Lastly, due to limited literature on the optimal strategy for VTE risk mitigation in patients who engage in long-distance travel either pre- or post-operatively, the choice of prophylactic agent should be individualized, taking into account the relative risks and benefits of different pharmacological and non-pharmacological options for each patient.
Strength of Recommendation: Limited.
Rationale: Although air travel and orthopaedic surgery, especially joint replacement surgery, are both well documented risk factors for the development of VTE, neither the American Academy of Orthopaedic Surgeons (AAOS) nor the American College of Chest Physicians (ACCP) have published guidelines regarding the safety of flying in the early postoperative period. The Center for Disease Control and Prevention (CDC) noted that there are “combined effects observed between these established risk factors and different forms of travel”, but also do not provide an evidence-based justification of this recommendation, largely due to the dearth of literature on this subject1.
Air travel and risk of venous thromboembolism (VTE): A large body of literature on the topic of air travel as a risk factor for VTE currently exists, dating back to the early 1950’s when VTE was first termed “economy class syndrome” by John Homans2,3. One meta-analysis found that air travel was associated with a nearly 3-fold increased risk of VTE, with a dose-response relationship of 18% higher risk for each 2-hour increase in travel duration4. Another meta-analysis of 14 studies involving over 4,000 episodes of deep venous thrombosis (DVT) demonstrated a relative risk of 2.8 (95% confidence interval [CI] 2.2 – 3.7) for long-duration flights5. A study in the New England Journal of Medicine corroborated this finding, noting that a greater distance traveled was a significant risk factor for pulmonary embolism (PE), with an incidence of 4.8 cases/million for those traveling more than 10,000 km compared to 1.5 cases/million for those traveling greater than 5,000 km, and 0.01 cases/million for those traveling less than 5,000 km6. In a case-control study on the topic of long-haul flights (> 8 hours), the relative risk of VTE was found to be 2.8 (95% CI 1.46 – 5.49) for travelers, although the authors noted that all flight-associated thromboses occurred exclusively in passengers with at least one established risk factor for venous thrombosis7. In one of the largest population-based case-control studies the Multiple Environmental and Genetic Assessment (MEGA) study, the authors found that traveling increased risk of VTE 2-fold (odds ratio [OR] 2.1, 95% CI 1.5 – 3.0), and the risk of flying was similar to the risk of traveling by car, bus or train. There was also an additive risk for those with predisposing factors for VTE, as it was found that travel, led to an even higher risk of VTE in individuals with factor V Leiden (OR 8.1, 95% CI 2.7 – 24.7), those with a body mass index (BMI) of > 30kg/m2 (OR 9.9, 95% CI 3.6 – 27.6) and those who were taking oral contraceptive pills (OCP) (OR > 20)8. It was also shown that the risk of developing VTE increased by almost 20 times among passengers who had recently undergone surgery when compared to passengers who had not (OR 19.8)5. The extent of additional risk contributed by these different risk factors, however, was not clear.
Cooper et al., performed a retrospective cohort study of 1,465 consecutive total joint arthroplasty (TJA) patients, which comprised 220 patients (15%) who took a flight home at a mean of 2.9 days after surgery (range, 1 – 10 days) and a control group of 1,245 patients (85%) who did not. The authors found no difference in the rate of DVT, PE, or VTE between the groups, with the caveat that all patients received appropriate risk-stratified VTE prophylaxis after surgery1. Another retrospective review examined 608 patients who had extended travel for an average of 1,377 miles and 6.5 days after total hip arthroplasty (THA) and received appropriate DVT prophylaxis. There were no deaths or symptomatic PE in the study and only 5 (0.82%) symptomatic DVT and 9 (1.5%) bleeding complications occurred9.
Timing: Regarding the timing of diagnosis of VTE in relation to travel, the abovementioned MEGA study found that of the 233 events that occurred within 8 weeks of travel, 29% were diagnosed in the first week, after which the incidence gradually decreased8. This pattern was also described in a separate study from Australia, thus supporting a causal relation10. Two additional studies found that the majority of VTE occurred within the first 2 weeks after landing, with a mean interval of 4 days, although the risk was present for up to 8 weeks5,11,12. In the single paper that examined the impact of preoperative travel on the risk of VTE in patients who were scheduled to receive a TJA, Citak et al., compared 155 patients (87 THA, 68 total knee arthroplasties [TKA]) to 187 patients (92 THA, 95 TKA) without bus, air or car travel for longer than 30 minutes. The study found that patients with preoperative air travel were not at higher risk of VTE compared to patients without preoperative air travel who underwent TKA (hazard ratio [HR] = 0.95; 95% CI = 0.14 – 6.52)13.
Prophylaxis: The ninth edition of the ACCP guidelines from 2012 suggested the following preventive measures for patients deemed to be at risk of VTE on long-haul flights: walking, calf muscle exercises, and aisle seating (evidence level 2C)14 cited in15. A recent Cochrane review of 11 randomized studies with a total of 2,906 patients (1,273 high-risk patients) on flights lasting more than 5 hours concluded that there was high-quality evidence demonstrating a reduction in the incidence of asymptomatic DVT, and moderate-quality evidence demonstrating a reduction in superficial venous thrombosis following the use of graduated elastic compression stockings16. Furthermore, the ACCP guidelines suggested that passengers on long-haul flights who are at risk of VTE should wear below the knee compression stockings providing 15 to 30 mmHg of pressure at the ankle during the flight (evidence level 2C).
No consensus has been reached in regards to pharmacologic prophylaxis, and this should be prescribed on a case-by-case basis. Antiplatelets did not prove to be an effective prophylactic agent for primary or secondary long-haul flight-related VTE11,17, cited in15,18; cited in19. While the LONFIT-3 study suggested that the risk of VTE could be eliminated by taking low-molecular-weight heparin (LMWH), there is still a lack of evidence supporting its widespread use in this situation17,20, cited in15. Direct oral anticoagulants (DOAC) have theoretical benefits given their short half-lives, rapid onset of action, and oral administration. In a retrospective review of over 600 patients flying an average of 6.5 days after THA, who were prescribed anticoagulants such as enoxaparin, dalteparin, fondaparinux or warfarin, no deaths or symptomatic PE were reported, and only 5 (0.82%) symptomatic DVT and 9 (1.5%) bleeding complications occurred9.
Conclusion: Extended travel, whether by air, car, or train, has been associated with a higher risk of VTE in the general population because of the limited movement in a seated position, which may lead to positional lower extremity venous stasis. This risk is further exacerbated in comorbid conditions such as obesity and Factor V Leiden deficiency. Long-haul travel beyond 6 to 8 hours is associated with a dose-response increase in the rate of VTE because of a prolonged reduction in venous outflow. Similarly, joint replacement surgery is associated with an elevated risk of VTE in the postoperative period. Notwithstanding, there is no conclusive evidence to suggest that these independent risks are additive when the two exposures temporally related (i.e., extended travel before or after lower extremity arthroplasty surgery). Studies have suggested that a greater protection against VTE is afforded with the use of more potent anticoagulants in favor of antiplatelet agents when long-haul travel occurs within 6 weeks after surgery. The overall recommendation is therefore to individualize the VTE prophylaxis strategy in patients who choose to undergo extended travel in the perioperative period, and surgeons should consider the use of oral anticoagulants in patients who carry additional thrombotic risk factors.
1. Cooper HJ, Sanders SA, Berger RA. Risk of symptomatic venous thromboembolism associated with flying in the early postoperative period following elective total hip and knee arthroplasty. J Arthroplasty. 2014;29(6):1119-1122. doi:10.1016/j.arth.2014.01.005
2. Cruickshank JM, Gorlin R, Jennett B. Air travel and thrombotic episodes: the economy class syndrome. Lancet. 1988;2(8609):497-498. doi:10.1016/s0140-6736(88)90134-1
3. Homans J. Thrombosis of the deep leg veins due to prolonged sitting. N Engl J Med. 1954;250(4):148-149. doi:10.1056/NEJM195401282500404
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6. Lapostolle F, Surget V, Borron SW, et al. Severe pulmonary embolism associated with air travel. N Engl J Med. 2001;345(11):779-783. doi:10.1056/NEJMoa010378
7. Schwarz T, Siegert G, Oettler W, et al. Venous thrombosis after long-haul flights. Arch Intern Med. 2003;163(22):2759-2764. doi:10.1001/archinte.163.22.2759
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13. Citak M, Klatte TO, Suero EM, Lenhart J, Gehrke T, Kendoff D. Are patients with preoperative air travel at higher risk for venous thromboembolism following primary total hip and knee arthroplasty? Technol Health Care. 2015;23(3):307-311. doi:10.3233/THC-150893
14. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e152S-e184S. doi:10.1378/chest.11-2295
15. Marques MA, Panico MDB, Porto CLL, Milhomens AL de M, Vieira J de M. Venous thromboembolism prophylaxis on flights. J Vasc Bras. 2018;17(3):215-219. doi:10.1590/1677-5449.010817
16. Clarke MJ, Broderick C, Hopewell S, Juszczak E, Eisinga A. Compression stockings for preventing deep vein thrombosis in airline passengers. Cochrane Database Syst Rev. 2021;4:CD004002. doi:10.1002/14651858.CD004002.pub4
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20. Toff WD, Sugerman H, Eklöf BG. Venous thrombosis related to air travel–reply. JAMA. 2013;309(13):1347. doi:10.1001/jama.2013.1343