Fright of Long-Haul Flights: Focus on Travel-Associated Thrombosis

Abstract

Travel-related thrombosis (TRT), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), poses a significant health risk associated with long-haul travel. Prolonged immobility, dehydration, and cabin pressure changes during flights contribute to venous stasis, hypoxia, and hypercoagulability, collectively increasing the risk of venous thromboembolism (VTE). While the absolute risk of TRT is relatively low in the population overall, it rises significantly among high-risk groups, including individuals with a history of VTE, thrombophilia, pregnancy, or recent surgery. This review explores the epidemiology, pathophysiology, clinical presentation, and diagnostic evaluation of TRT while highlighting the importance of early recognition and prevention. Risk assessment models can provide guidance for identifying at-risk travelers. Preventive strategies include pharmacological prophylaxis with low-molecular-weight heparin (LMWH) for high-risk individuals and nonpharmacological measures such as compression stockings, intermittent pneumatic compression, mobility exercises, and hydration. Guidelines from international societies recommend tailored interventions based on individual risk profiles, as randomized controlled trials are scarce. Given that long-haul travel dramatically expands, this review critically analyzes the available TRT management strategies in various clinical settings, aiming to increase awareness of this global health issue.

Keywords

thrombosis - venous thromboembolism - pulmonary embolism - risk factors - risk assessment - prevention strategies

Publikationsverlauf

Artikel online veröffentlicht:
27. Februar 2025

• References

• 1 Kuipers S, Schreijer AJ, Cannegieter SC, Büller HR, Rosendaal FR, Middeldorp S. Travel and venous thrombosis: a systematic review. J Intern Med 2007; 262 (06) 615-634
• 2 Brill A. Multiple facets of venous thrombosis. Int J Mol Sci 2021; 22 (08) 3853
• 3 Şabanoğlu C. The secret enemy during a flight: economy class syndrome. Anatol J Cardiol 2021; 25 (Suppl. 01) 13-17
• 4 Kakkos SK, Geroulakos G. Economy class stroke syndrome: case report and review of the literature. Eur J Vasc Endovasc Surg 2004; 27 (03) 239-243
• 5 Symington IS, Stack BH. Pulmonary thromboembolism after travel. Br J Dis Chest 1977; 71 (02) 138-140
• 6 Homans J. Thrombosis of the deep leg veins due to prolonged sitting. N Engl J Med 1954; 250 (04) 148-149
• 7 Milne R. Venous thromboembolism and travel: is there an association?. J R Coll Physicians Lond 1992; 26 (01) 47-49
• 8 Landgraf H, Vanselow B, Schulte-Huermann D, Mülmann MV, Bergau L. Economy class syndrome: rheology, fluid balance, and lower leg edema during a simulated 12-hour long distance flight. Aviat Space Environ Med 1994; 65 (10 Pt 1): 930-935
• 9 House of Lords. Science and Technology Committee. Air Travel and Health: an Update. Report and Evidence. The Stationery Office Ltd., London, 2007. Accessed January 2025 at: https://publications.parliament.uk/pa/ld200708/ldselect/ldsctech/7/7.pdf
• 10 Jacobson BF, Münster M, Smith A. et al. The BEST study–a prospective study to compare business class versus economy class air travel as a cause of thrombosis. S Afr Med J 2003; 93 (07) 522-528
• 11 Kuipers S, Venemans A, Middeldorp S, Büller HR, Cannegieter SC, Rosendaal FR. The risk of venous thrombosis after air travel: contribution of clinical risk factors. Br J Haematol 2014; 165 (03) 412-413
• 12 Chandra D, Parisini E, Mozaffarian D. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med 2009; 151 (03) 180-190
• 13 Kuipers S, Cannegieter SC, Middeldorp S, Robyn L, Büller HR, Rosendaal FR. The absolute risk of venous thrombosis after air travel: a cohort study of 8,755 employees of international organisations. PLoS Med 2007; 4 (09) e290
• 14 Lapostolle F, Surget V, Borron SW. et al. Severe pulmonary embolism associated with air travel. N Engl J Med 2001; 345 (11) 779-783
• 15 WHO Research into Global Hazards of Travel (WRIGHT) project: final report of phase I. Final report of phase I. World Health Organization 2007. Accessed January 2025 at: https://iris.who.int/bitstream/handle/10665/43684/9789241595537_eng.pdf?sequence=1&isallowed=y
• 16 Martinelli I, Taioli E, Battaglioli T. et al. Risk of venous thromboembolism after air travel: interaction with thrombophilia and oral contraceptives. Arch Intern Med 2003; 163 (22) 2771-2774
• 17 MacCallum PK, Ashby D, Hennessy EM. et al. Cumulative flying time and risk of venous thromboembolism. Br J Haematol 2011; 155 (05) 613-619
• 18 Arfvidsson B, Eklof B, Kistner RL, Masuda EM, Sato DT. Risk factors for venous thromboembolism following prolonged air travel. Coach class thrombosis. Hematol Oncol Clin North Am 2000; 14 (02) 391-400 , ix
• 19 Philbrick JT, Shumate R, Siadaty MS, Becker DM. Air travel and venous thromboembolism: a systematic review. J Gen Intern Med 2007; 22 (01) 107-114
• 20 Tourn J, Crescence L, Bruzzese L, Panicot-Dubois L, Dubois C. Cellular and molecular mechanisms leading to air travel-induced thrombosis. Circ Res 2025; 136 (01) 115-134
• 21 Schreijer AJ, Cannegieter SC, Meijers JC, Middeldorp S, Büller HR, Rosendaal FR. Activation of coagulation system during air travel: a crossover study. Lancet 2006; 367 (9513): 832-838
• 22 Piazza G. Beyond Virchow's Triad: does cardiovascular inflammation explain the recurrent nature of venous thromboembolism?. Vasc Med 2015; 20 (02) 102-104
• 23 Sándor T. Travel thrombosis: pathomechanisms and clinical aspects. Pathophysiology 2008; 15 (04) 243-252
• 24 Krasiński Z, Chou A, Stępak H. COVID-19, long flights, and deep vein thrombosis: what we know so far. Cardiol J 2021; 28 (06) 941-953
• 25 Humphreys S, Deyermond R, Bali I, Stevenson M, Fee JP. The effect of high altitude commercial air travel on oxygen saturation. Anaesthesia 2005; 60 (05) 458-460
• 26 Nagda NL, Hodgson M. Low relative humidity and aircraft cabin air quality. Indoor Air 2001; 11 (03) 200-214
• 27 Kraus C, Kadriu B, Lanzenberger R, Zarate Jr CA, Kasper S. Prognosis and improved outcomes in major depression: a review. Transl Psychiatry 2019; 9 (01) 127
• 28 Hoirisch-Clapauch S, Nardi AE, Gris JC, Brenner B. Coagulation and mental disorders. Rambam Maimonides Med J 2014; 5 (04) e0036
• 29 Austin AW, Wissmann T, von Kanel R. Stress and hemostasis: an update. Semin Thromb Hemost 2013; 39 (08) 902-912
• 30 Halleux CM, Declerck PJ, Tran SL, Detry R, Brichard SM. Hormonal control of plasminogen activator inhibitor-1 gene expression and production in human adipose tissue: stimulation by glucocorticoids and inhibition by catecholamines. J Clin Endocrinol Metab 1999; 84 (11) 4097-4105
• 31 Lang UE, Borgwardt S. Molecular mechanisms of depression: perspectives on new treatment strategies. Cell Physiol Biochem 2013; 31 (06) 761-777
• 32 Lopez-Vilchez I, Serra-Millas M, Navarro V. et al. Prothrombotic platelet phenotype in major depression: downregulation by antidepressant treatment. J Affect Disord 2014; 159: 39-45
• 33 Lahlou-Laforet K, Alhenc-Gelas M, Pornin M. et al. Relation of depressive mood to plasminogen activator inhibitor, tissue plasminogen activator, and fibrinogen levels in patients with versus without coronary heart disease. Am J Cardiol 2006; 97 (09) 1287-1291
• 34 Tsantes AE, Nikolopoulos GK, Bagos PG, Bonovas S, Kopterides P, Vaiopoulos G. The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk. Thromb Res 2008; 122 (06) 736-742
• 35 McIntosh IB, Swanson V, Power KG, Raeside F, Dempster C. Anxiety and health problems related to air travel. J Travel Med 1998; 5 (04) 198-204
• 36 Carreira-Míguez M, Navarro-Jiménez E, Clemente-Suárez VJ. Behavioral patterns of depression patients and control population. Int J Environ Res Public Health 2022; 19 (15) 9506
• 37 Ströhle A. Physical activity, exercise, depression and anxiety disorders. J Neural Transm (Vienna) 2009; 116 (06) 777-784
• 38 Penninx BW, Pine DS, Holmes EA, Reif A. Anxiety disorders. Lancet 2021; 397 (10277): 914-927
• 39 Brenner B. Interventions to prevent venous thrombosis after air travel, are they necessary? Yes. J Thromb Haemost 2006; 4 (11) 2302-2305
• 40 Mendis S, Yach D, Alwan A. Air travel and venous thromboembolism. Bull World Health Organ 2002; 80 (05) 403-406
• 41 Dubois-Silva Á, Barbagelata-López C, Piñeiro-Parga P. et al; RIETE Investigators. Deep vein thrombosis symptoms and 30-day mortality in acute pulmonary embolism. Eur J Intern Med 2023; 108: 43-51
• 42 Mackman N. New insights into the mechanisms of venous thrombosis. J Clin Invest 2012; 122 (07) 2331-2336
• 43 Kahn SR, Lim W, Dunn AS. et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141 (Suppl. 02) e195S-e226S
• 44 Tovey C, Wyatt S. Diagnosis, investigation, and management of deep vein thrombosis. BMJ 2003; 326 (7400): 1180-1184
• 45 Huisman MV, Tromeur C, Le Gal G, Le Roux PY, Righini M. Diagnostic management of acute pulmonary embolism. Presse Med 2024; 53 (03) 104241
• 46 Patel H, Sun H, Hussain AN, Vakde T. Advances in the diagnosis of venous thromboembolism: a literature review. Diagnostics (Basel) 2020; 10 (06) 365
• 47 Eklöf B, Maksimovic D, Caprini JA, Glase C. Air travel-related venous thromboembolism. Dis Mon 2005; 51 (2-3): 200-207
• 48 Mercer A, Brown JD. Venous thromboembolism associated with air travel: a report of 33 patients. Aviat Space Environ Med 1998; 69 (02) 154-157
• 49 Schobersberger W, Fries D, Mittermayr M. et al. Changes of biochemical markers and functional tests for clot formation during long-haul flights. Thromb Res 2002; 108 (01) 19-24
• 50 Schreijer AJ, Hoylaerts MF, Meijers JC. et al. Explanations for coagulation activation after air travel. J Thromb Haemost 2010; 8 (05) 971-978
• 51 Kearon C, Akl EA, Comerota AJ. et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141 (Suppl. 02) e419S-e496S
• 52 Seed SM, Khov SL, Binguad FS, Abraham GM, Aungst TD. Identification and review of mobile applications for travel medicine practitioners and patients. J Travel Med 2016; 23 (04) taw034
• 53 Ferretti A, Hedrich N, Lovey T, Vayena E, Schlagenhauf P. Mobile apps for travel medicine and ethical considerations: a systematic review. Travel Med Infect Dis 2021; 43: 102143
• 54 Flaherty GT, Hamer DH, Chen LH. Travel in the time of COVID: a review of international travel health in a global pandemic. Curr Infect Dis Rep 2022; 24 (10) 129-145
• 55 Coughlin SS, Stewart J. Use of consumer wearable devices to promote physical activity: a review of health intervention studies. J Environ Health Sci 2016;2(06):
• 56 Hayssen H, Cires-Drouet R, Englum B. et al. Systematic review of venous thromboembolism risk categories derived from Caprini score. J Vasc Surg Venous Lymphat Disord 2022; 10 (06) 1401-1409.e7
• 57 van Belle A, Büller HR, Huisman MV. et al; Christopher Study Investigators. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA 2006; 295 (02) 172-179
• 58 Wells PS, Anderson DR, Bormanis J. et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997; 350 (9094): 1795-1798
• 59 Pandor A, Tonkins M, Goodacre S. et al. Risk assessment models for venous thromboembolism in hospitalised adult patients: a systematic review. BMJ Open 2021; 11 (07) e045672
• 60 McKerrow Johnson I, Shatzel J, Olson S, Kohl T, Hamilton A, DeLoughery TG. Travel-associated venous thromboembolism. Wilderness Environ Med 2022; 33 (02) 169-178
• 61 Chamnanchanunt S, Rojnuckarin P. Direct oral anticoagulants and travel-related venous thromboembolism. Open Med (Wars) 2018; 13: 575-582
• 62 Kuipers S, Cannegieter SC, Middeldorp S, Rosendaal FR, Büller HR. Use of preventive measures for air travel-related venous thrombosis in professionals who attend medical conferences. J Thromb Haemost 2006; 4 (11) 2373-2376
• 63 Kakkos S, Kirkilesis G, Caprini JA. et al. Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism. Cochrane Database Syst Rev 2022; 1 (01) CD005258
• 64 Olsen JHH, Öberg S, Rosenberg J. The effect of compression stocking on leg edema and discomfort during a 3-hour flight: a randomized controlled trial. Eur J Intern Med 2019; 62: 54-57
• 65 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 (04) CD004002
• 66 Geerts WH, Bergqvist D, Pineo GF. et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008; 133 (Suppl. 6) 381S-453S
• 67 Hitos K, Cannon M, Cannon S, Garth S, Fletcher JP. Effect of leg exercises on popliteal venous blood flow during prolonged immobility of seated subjects: implications for prevention of travel-related deep vein thrombosis. J Thromb Haemost 2007; 5 (09) 1890-1895
• 68 Powell-Dunford N, Adams JR, Grace C. Medical advice for commercial air travel. Am Fam Physician 2021; 104 (04) 403-410
• 69 Couch RD. Travel, time zones, and sudden cardiac death. Emporiatric pathology. Am J Forensic Med Pathol 1990; 11 (02) 106-111
• 70 Schmitt HE, Mihatsch MJ. Thrombosis of the popliteal vein. Cardiovasc Intervent Radiol 1992; 15 (04) 234-239
• 71 Teenan RP, McKay AJ. Peripheral arterial thrombosis related to commercial airline flights: another manifestation of the economy class syndrome. Br J Clin Pract 1992; 46 (03) 165-166
• 72 Kakkos SK, Gohel M, Baekgaard N. et al; Esvs Guidelines Committee. Editor's choice - European Society for Vascular Surgery (ESVS) 2021 clinical practice guidelines on the management of venous thrombosis. Eur J Vasc Endovasc Surg 2021; 61 (01) 9-82
• 73 Schunemann HJ, Cushman M, Burnett AE. et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv 2023; 7 (09) 1671
• 74 Thrombosis Canada. 2023 Air Travel-Related Thrombosis – Guidelines. Accessed January 2025 at: https://thrombosiscanada.ca/clinical_guides/pdfs/91_20.pdf
• 75 Watson HG, Baglin TP. Guidelines on travel-related venous thrombosis. Br J Haematol 2011; 152 (01) 31-34
• 76 Riat R. Addendum to Guidelines on travel-related venous thrombosis. Accessed January 2025 at: https://b-s-h.org.uk/media/exvd4gap/2023-11-15-bsh-addendum1-travel-related-thrombosis.pdf
• 77 ACOG Committee Opinion No. ACOG committee opinion no. 746 summary: air travel during pregnancy. Obstet Gynecol 2018; 132 (02) 533-534
• 78 Ali MAM, Spinler SA. COVID-19 and thrombosis: from bench to bedside. Trends Cardiovasc Med 2021; 31 (03) 143-160
• 79 Brito-Dellan N, Tsoukalas N, Font C. Thrombosis, cancer, and COVID-19. Support Care Cancer 2022; 30 (10) 8491-8500
• 80 Scutelnic A, van de Munckhof A, Miraclin AT. et al. Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19. Eur Stroke J 2024; 9 (03) 676-686
• 81 Oldenburg J, Klamroth R, Langer F. et al. Diagnosis and management of vaccine-related thrombosis following AstraZeneca COVID-19 vaccination: guidance statement from the GTH. Hamostaseologie 2021; 41 (03) 184-189
• 82 Iba T, Levy JH. Thrombosis and thrombocytopenia in COVID-19 and after COVID-19 vaccination. Trends Cardiovasc Med 2022; 32 (05) 249-256
• 83 Lippi G, Favaloro EJ. Cerebral venous thrombosis developing after COVID-19 vaccination: VITT, VATT, TTS, and more. Semin Thromb Hemost 2022; 48 (01) 8-14
• 84 Izadi M, Alemzadeh-Ansari MJ, Kazemisaleh D, Moshkani-Farahani M, Shafiee A. Do pregnant women have a higher risk for venous thromboembolism following air travel?. Adv Biomed Res 2015; 4: 60
• 85 Ram S, Shalev-Ram H, Neuhof B. et al. Air travel during pregnancy and the risk of venous thrombosis. Am J Obstet Gynecol MFM 2023; 5 (01) 100751
• 86 Hillen HF. Thrombosis in cancer patients. Ann Oncol 2000; 11 (Suppl. 03) 273-276
• 87 Wang R, Tang LV, Hu Y. Genetic factors, risk prediction and AI application of thrombotic diseases. Exp Hematol Oncol 2024; 13 (01) 89
• 88 Harbsmeier AN, Altintas I, Iversen K, Andersen O, Nehlin JO. Biomarkers and the post-thrombotic syndrome: a systematic review of biomarkers associated with the occurrence of the post-thrombotic syndrome after lower extremity deep venous thrombosis. Phlebology 2023; 38 (09) 577-598
• 89 Cross B, Turner RM, Zhang JE, Pirmohamed M. Being precise with anticoagulation to reduce adverse drug reactions: are we there yet?. Pharmacogenomics J 2024; 24 (02) 7
• 90 Ding J, Yue X, Tian X, Liao Z, Meng R, Zou M. Association between inflammatory biomarkers and venous thromboembolism: a systematic review and meta-analysis. Thromb J 2023; 21 (01) 82
• 91 Bannoud MA, Martins TD, Montalvão SAL, Annichino-Bizzacchi JM, Filho RM, Maciel MRW. Integrating biomarkers for hemostatic disorders into computational models of blood clot formation: a systematic review. Math Biosci Eng 2024; 21 (12) 7707-7739
• 92 Wikan VE, Tøndel BG, Morelli VM, Brodin EE, Brækkan SK, Hansen JB. Diagnostic blood biomarkers for acute pulmonary embolism: a systematic review. Diagnostics (Basel) 2023; 13 (13) 2301
• 93 Radanliev P, De Roure D, Walton R. et al. COVID-19 what have we learned? The rise of social machines and connected devices in pandemic management following the concepts of predictive, preventive and personalized medicine. EPMA J 2020; 11 (03) 311-332
• 94 Shah N, Costello K, Mehta A, Kumar D. Applications of digital health technologies in knee osteoarthritis: narrative review. JMIR Rehabil Assist Technol 2022; 9 (02) e33489
• 95 Cannard C, Brandmeyer T, Wahbeh H, Delorme A. Self-health monitoring and wearable neurotechnologies. Handb Clin Neurol 2020; 168: 207-232
• 96 Shaffer F, Meehan ZM. A practical guide to resonance frequency assessment for heart rate variability biofeedback. Front Neurosci 2020; 14: 570400