Vol 28, No 6 (2021)
Review Article
Published online: 2021-08-02

open access

Page views 8735
Article views/downloads 1929
Get Citation

Connect on Social Media

Connect on Social Media

COVID-19, long flights, and deep vein thrombosis: What we know so far

Zbigniew Krasiński1, Andre Chou1, Hubert Stępak1
Pubmed: 34355776
Cardiol J 2021;28(6):941-953.

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) pandemic has presently stunted the growth of the airline industry. Despite the setbacks, pre-COVID-19 passenger numbers are forecasted to return by as early as 2024. As the industry recovers, the number of long-distance flights will surely continue to increase like it did before the pandemic. The incidence of venous thromboembolism (VTE) following air travel is also likely to increase. Although not common, the unique environment of air travel exposes individuals with particular health conditions to an elevated risk of acquiring VTEs. Numerous factors increasing the risk of developing VTE related to air travel have been identified, including inherited and acquired flight-related aspects. Non-pharmacological approaches to reduce air travel-related VTEs involve simple foot movements, compression socks and stockings, intermittent pneumatic compression devices, a novel modified airline seat, and foot exercisers. Pharmacological methods include heparins and direct oral anticoagulants. More than 30 reliable articles were evaluated to present the current knowledge regarding air travel-related VTEs, their risk factors, and prophylactic methods. Issues in research methodologies found in the literature were identified and discussed. Further research involving international collaboration projects is recommended. The authors’ perspectives regarding long flights in previously infected COVID-19 individuals are also included.

Article available in PDF format

View PDF Download PDF file

References

  1. International Air Transport Association. 20 Year Passenger Forecast [Internet]. www.iata.org. 2020. https://www.iata.org/en/publications/store/20-year-passenger-forecast/.
  2. Bowler T. Carbon fibre planes: Lighter and stronger by design. BBC News [Internet]. 2014 Jan 28. https://www.bbc.com/news/business-25833264 (cited 2018 Jul 7).
  3. Annual growth in global air traffic passenger demand from 2005 to 2018. Statista [Internet]. 2018 Jun 1. https://www.statista.com/statistics/193533/growth-of-global-air-traffic-passenger-demand/ (https://www.bbc.com/news/business-25833264).
  4. Simpson K. Shelter deaths from pulmonary embolism. Lancet. 1940; 236(6120): 744.
  5. Homans J. Thrombosis of the deep leg veins due to prolonged sitting. N Engl J Med. 1954; 250(4): 148–149.
  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.
  7. Scurr J, Machin S, Bailey-King S, et al. Frequency and prevention of symptomless deep-vein thrombosis in long-haul flights: a randomised trial. The Lancet. 2001; 357(9267): 1485–1489.
  8. Watson HG. Travel and thrombosis. Blood Rev. 2005; 19(5): 235–241.
  9. Sándor T. Travel thrombosis: Pathomechanisms and clinical aspects. Pathophysiology. 2008; 15(4): 243–252.
  10. Nicolaides AN. Thromboembolism: etiology, advances in prevention, and management. University Park Press, Baltimore 1975: 348.
  11. Parsi K, McGrath MA, Lord RSA. Traveller’s Venous Thromboembolism: A Review of World Literature, a Survey of World Airlines and an Australian Perspective. Australian New Zealand J Phlebology. 2001; 5(1): 32–53.
  12. Schobersberger W, Schobersberger B, Mittermayr M, et al. Air travel, hypobaric hypoxia, and prothrombotic changes. JAMA. 2006; 296(19): 2313–4; author reply 2314.
  13. Dusse LM, Silva MV, Freitas LG, et al. Economy class syndrome: what is it and who are the individuals at risk? Rev Bras Hematol Hemoter. 2017; 39(4): 349–353.
  14. Landgraf H, Vanselow B, Schulte-Huermann D, et al. 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.
  15. Schreijer AJM, Cannegieter SC, Doggen CJM, et al. The effect of flight-related behaviour on the risk of venous thrombosis after air travel. Br J Haematol. 2009; 144(3): 425–429.
  16. Tao K, Davenport M. Deep venous thromboembolism in a triathlete. J Emerg Med. 2010; 38(3): 351–353.
  17. Getzin AR, Silberman MR. Iliac artery flow limitations in endurance athletes. Curr Sports Med Rep. 2010; 9(6): 334–337.
  18. Béliard S, Feuvrier D, Ducroux E, et al. May Thurner syndrome revealed by left calf venous claudication during running, a case report. BMC Sports Sci Med Rehabil. 2018; 10: 3.
  19. Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016; 41(1): 3–14.
  20. Lapostolle F, Le Toumelin P, Chassery C, et al. Gender as a risk factor for pulmonary embolism after air travel. Thromb Haemost. 2009; 102(6): 1165–1168.
  21. Geerts W, Bergqvist D, Pineo G, et al. Prevention of venous thromboembolism. Chest. 2008; 133(6): 3815–4535.
  22. Nopp S, Moik F, Jilma B, et al. Risk of venous thromboembolism in patients with COVID-19: A systematic review and meta-analysis. Res Pract Thromb Haemost. 2020 [Epub ahead of print]; 4(7): 1178–1191.
  23. Parker S, Mahomed O. Hypoxia and thrombosis in COVID-19: new considerations for air passengers. J Travel Med. 2020; 27(8).
  24. Bartholomew JR, Schaffer JL, McCormick GF. Air travel and venous thromboembolism: minimizing the risk. Cleve Clin J Med. 2011; 78(2): 111–120.
  25. Kuipers S, Venemans A, Middeldorp S, et al. The risk of venous thrombosis after air travel: contribution of clinical risk factors. Br J Haematol. 2014; 165(3): 412–413.
  26. Bauer KA, Lip GY, Leung LLK, et al. Overview of the causes of venous thrombosis. Post TW, ed [Internet]. https://www.uptodate.com/contents/overview-of-the-causes-of-venous-thrombosis/ (cited 2019 Jul 13).
  27. Iqbal O, Eklof Bo, Tobu M, et al. Air travel-associated venous thromboembolism. Med Princ Pract. 2003; 12(2): 73–80.
  28. Cannegieter SC, Doggen CJM, van Houwelingen HC, et al. Travel-related venous thrombosis: results from a large population-based case control study (MEGA study). PLoS Med. 2006; 3(8): e307.
  29. Bauer KA, Leung LLK, Mahoney DH, Tirnauer JS. Protein S deficiency. Post TW, ed [Internet]. https://www.uptodate.com/contents/protein-s-deficiency/ (cited 2019 Jul 13).
  30. Presgrave P, Ma D. Genetic predisposition to venous thromboembolism: molecular basis and a practical guide to management. Australian New Zealand J Phlebology. 2000; 4: 39–45.
  31. Bauer KA, Leung LLK, Tirnauer JS. Antithrombin deficiency. Post TW, ed [Internet]. https://www.uptodate.com/contents/antithrombin-deficiency/.
  32. 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.
  33. de Groot PG, Lutters B, Derksen RH, et al. Lupus anticoagulants and the risk of a first episode of deep venous thrombosis. J Thromb Haemost. 2005; 3(9): 1993–1997.
  34. Alemzadeh-Ansari MJ, Kazemisaleh D, Moshkani-Farahani M, et al. Do pregnant women have a higher risk for venous thromboembolism following air travel? Adv Biomed Res. 2015; 4: 60.
  35. Heit JA, Kobbervig CE, James AH, et al. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med. 2005; 143(10): 697–706.
  36. Cannegieter SC, Rosendaal FR. Pregnancy and travel-related thromboembolism. Thromb Res. 2013; 131 Suppl 1: S55–S58.
  37. Brenner B. Interventions to prevent venous thrombosis after air travel, are they necessary? Yes. J Thromb Haemost. 2006; 4(11): 2302–2305.
  38. Reducing the Risk of Venous Thromboembolism during Pregnancy and the Puerperium [Internet]. Royal College of Obstetricians and Gynaecologists; 2015. https://www.rcog.org.uk/globalassets/documents/guidelines/gtg-37a.pdf (cited 2019 Jul 13).
  39. Meroni PL, Moia M, Derksen RH, et al. Venous thromboembolism in the antiphospholipid syndrome: management guidelines for secondary prophylaxis. Lupus. 2003; 12(7): 504–507.
  40. Naouri D, Lapostolle F, Rondet C, et al. Prevention of medical events during air travel: a narrative review. Am J Med. 2016; 129(9): 1000.e1–1000.e6.
  41. Long haul flight may have led to Jonah Lomu’s death. The New Zealand Herald [Internet]. 2015 Nov 23. https://www.nzherald.co.nz/sport/long-haul-flight-may-have-led-to-jonah-lomus-death/DWWBA7BFLUMHBEHVAYY5SNAECM/ (cited 2020 Dec 9).
  42. Abdollahi M, Cushman M, Rosendaal FR. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost. 2003; 89(3): 493–498.
  43. Liu F, Silva D, Malone MV, et al. MTHFR A1298C and C677T Polymorphisms Are Associated with Increased Risk of Venous Thromboembolism: A Retrospective Chart Review Study. Acta Haematol. 2017; 138(4): 208–215.
  44. Guba SC, Fink LM, Fonseca V. Hyperhomocysteinemia. An emerging and important risk factor for thromboembolic and cardiovascular disease. Am J Clin Pathol. 1996; 106(6): 709–722.
  45. Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol. 2000; 151(9): 862–877.
  46. den Heijer M, Koster T, Blom HJ, et al. Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med. 1996; 334(12): 759–762.
  47. Lievers KJ, Boers GH, Verhoef P, et al. A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk. J Mol Med (Berl). 2001; 79(9): 522–528.
  48. Schwarz T, Siegert G, Oettler W, et al. Venous thrombosis after long-haul flights. Arch Intern Med. 2003; 163(22): 2759–2764.
  49. Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1995; 346(8990): 1575–1582.
  50. Contraceptive Use. In: National Survey of Family Growth [Internet]. https://www.cdc.gov/nchs/fastats/contraceptive.htm.
  51. Arya R, Barnes JA, Hossain U, et al. Long-haul flights and deep vein thrombosis: a significant risk only when additional factors are also present. Br J Haematol. 2002; 116(3): 653–654.
  52. Pérez-Rodríguez E, Jiménez D, Díaz G, et al. Incidence of air travel-related pulmonary embolism at the Madrid-Barajas airport. Arch Intern Med. 2003; 163(22): 2766–2770.
  53. Chandra D, Parisini E, Mozaffarian D. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med. 2009; 151(3): 180–190.
  54. Belcaro G, Cesarone MR, Dugall M, et al. Venous Thromboembolism from Air Travel: The LONFLIT Studies. In: Shirato K, editor. Venous Thromboembolism [Internet]. Tokyo: Springer-Verlag; 2005, p. 103-116. http://link.springer.com/10.1007/4-431-27121-X_10 (cited 2018 Nov 24).
  55. 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(7): 522–528.
  56. Chee YL, Watson HG. Air travel and thrombosis. Br J Haematol. 2005; 130(5): 671–680.
  57. Domingueti CP, Dusse LM, Carvalho Md, et al. Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. J Diabetes Complications. 2016; 30(4): 738–745.
  58. Belcaro G, Stansby G, Nicolaides AN. The Venous Clinic. Imperial College Press, London 1999.
  59. Belcaro G, Geroulakos G, Nicolaides AN, et al. Venous thromboembolism from air travel: the LONFLIT study. Angiology. 2001; 52(6): 369–374.
  60. Belcaro G, Cesarone MR, Rohdewald P, et al. Prevention of venous thrombosis and thrombophlebitis in long-haul flights with pycnogenol. Clin Appl Thromb Hemost. 2004; 10(4): 373–377.
  61. Bartholomew JR, Evans NS. Travel-related venous thromboembolism. Vasc Med. 2019; 24(1): 93–95.
  62. Pomp ER, Rosendaal FR, Doggen CJM. Smoking increases the risk of venous thrombosis and acts synergistically with oral contraceptive use. Am J Hematol. 2008; 83(2): 97–102.
  63. Morio H. Pulmonary Thromboembolism Associated with Air Travel in Jaan. In: Shirato K, editor. Venous Thromboembolism. Springer, Tokyo 2005: 87–93.
  64. Parsi K. Traveller’s Venous Thromboembolism [Master of Science (Medicine)]. University of New South Wales, Sydney 2001.
  65. White R, Keenan C. Effects of race and ethnicity on the incidence of venous thromboembolism. Thromb Res. 2009; 123: S11–S17.
  66. Keenan CR, White RH. The effects of race/ethnicity and sex on the risk of venous thromboembolism. Curr Opin Pulm Med. 2007; 13(5): 377–383.
  67. Inflight wellbeing. Air New Zealand [Internet]. https://www.airnewzealand.co.nz/inflight-wellbeing (cited 2018 Aug 7).
  68. Hitos K, Cannon M, Cannon S, et al. 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(9): 1890–1895.
  69. Chen AH, Frangos SG, Kilaru S, et al. Intermittent pneumatic compression devices -- physiological mechanisms of action. Eur J Vasc Endovasc Surg. 2001; 21(5): 383–392.
  70. Belcaro G, Cesarone MR, Nicolaides AN, et al. Prevention of venous thrombosis with elastic stockings during long-haul flights: the LONFLIT 5 JAP study. Clin Appl Thromb Hemost. 2003; 9(3): 197–201.
  71. Cesarone MR, Belcaro G, Nicolaides AN, et al. The LONFLIT4-Concorde--Sigvaris Traveno Stockings in Long Flights (EcoTraS) Study: a randomized trial. Angiology. 2003; 54(1): 1–9.
  72. Sajid MS, Tai NRM, Goli G, et al. Knee versus thigh length graduated compression stockings for prevention of deep venous thrombosis: a systematic review. Eur J Vasc Endovasc Surg. 2006; 32(6): 730–736.
  73. Cesarone MR, Belcaro G, Nicolaides AN, et al. Prevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trial. Angiology. 2003; 54(5): 531–539.
  74. Lurie F, Kistner RL, Eklof Bo, et al. Prevention of air travel-related deep venous thrombosis with mechanical devices: active foot movements produce similar hemodynamic effects. J Vasc Surg. 2006; 44(4): 889–891.
  75. Comerota AJ, Katz ML, White JV. Why does prophylaxis with external pneumatic compression for deep vein thrombosis fail? Am J Surg. 1992; 164(3): 265–268.
  76. Abramowitz HB, Gertz SD. Venous stasis, deep venous thrombosis and airline flight: can the seat be fixed? Ann Vasc Surg. 2007; 21(3): 267–271.
  77. Coleridge PD. Independent Clinical Trials. https://airogym.com/en/content/17-independent-clinical-trials (cited 2018 Nov 24).
  78. Paydar S, Sabetian G, Khalili H, et al. Management of Deep Vein Thrombosis (DVT) Prophylaxis in Trauma Patients. Bull Emerg Trauma. 2016; 4(1): 1–7.
  79. Pai M, Douketis JD. Prevention of venous thromboembolism in adult travelers. Post TW, ed [Internet]. https://www.uptodate.com/contents/prevention-of-venous-thromboembolism-in-adult-travelers (cited 2019 Jul 7).
  80. Bevis P, Smith F. Deep vein thrombosis. Surgery (Oxford). 2016; 34(4): 159–164.
  81. 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.
  82. Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005; 106(8): 2710–2715.
  83. Chamnanchanunt S, Rojnuckarin P. Direct Oral Anticoagulants and Travel-related Venous Thromboembolism. Open Med (Wars). 2018; 13: 575–582.
  84. Weitz JI, Bauersachs R, Beyer-Westendorf J, et al. EINSTEIN CHOICE Investigators. Two doses of rivaroxaban versus aspirin for prevention of recurrent venous thromboembolism. Rationale for and design of the EINSTEIN CHOICE study. Thromb Haemost. 2015; 114(3): 645–650.
  85. Clark SL, Onida S, Davies A. Long-haul travel and venous thrombosis: What is the evidence? Phlebology. 2018; 33(5): 295–297.
  86. Zhu Q, Zhou S, Liu Z. Fondaparinux and Direct Oral Anticoagulants. J Am Coll Cardiol. 2018; 71(15): 1710.
  87. National Clinical Guideline Centre (UK). Venous Thromboembolic Diseases: The Management of Venous Thromboembolic Diseases and the Role of Thrombophilia Testing [Internet]. London: Royal College of Physicians (UK); 2012. (National Institute for Health and Clinical Excellence: Guidance). http://www.ncbi.nlm.nih.gov/books/NBK132796/ (cited 2018 Jul 9).
  88. Wolowacz SE, Roskell NS, Plumb JM, et al. Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty. A meta-analysis. Thromb Haemost. 2009; 101(1): 77–85.
  89. Hughes RJ, Hopkins RJ, Hill S, et al. Frequency of venous thromboembolism in low to moderate risk long distance air travellers: the New Zealand Air Traveller's Thrombosis (NZATT) study. Lancet. 2003; 362(9401): 2039–2044.
  90. Ferrari E, Chevallier T, Chapelier A, et al. Travel as a risk factor for venous thromboembolic disease: a case-control study. Chest. 1999; 115(2): 440–444.
  91. Kraaijenhagen R, Haverkamp D, Koopman M, et al. Travel and risk of venous thrombosis. Lancet. 2000; 356(9240): 1492–1493.
  92. Aryal KR, Al-Khaffaf H. Venous thromboembolic complications following air travel: what's the quantitative risk? A literature review. Eur J Vasc Endovasc Surg. 2006; 31(2): 187–199.
  93. Stroup DF. Meta-analysis of Observational Studies in Epidemiology. A Proposal for Reporting. JAMA. 2000; 283(15): 2008.
  94. Tovey C, Wyatt S. Diagnosis, investigation, and management of deep vein thrombosis. BMJ. 2003; 326(7400): 1180–1184.
  95. Wells PS, Anderson DR, Rodger M, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003; 349(13): 1227–1235.
  96. Bell ML, Kenward MG, Fairclough DL, et al. Differential dropout and bias in randomised controlled trials: when it matters and when it may not. BMJ. 2013; 346: e8668.
  97. 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.
  98. Citak M, Klatte TO, Suero EM, et al. 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.
  99. Gajic O, Sprung J, Hall BA, et al. Fatal acute pulmonary embolism in a patient with pelvic lipomatosis after surgery performed after transatlantic airplane travel. Anesth Analg. 2004; 99(4): 1032–1034.
  100. Han H, Yang L, Liu R, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020; 58(7): 1116–1120.
  101. Helms J, Tacquard C, Severac F, et al. CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020; 46(6): 1089–1098.
  102. Schwarz T, Langenberg K, Oettler W, et al. Deep vein and isolated calf muscle vein thrombosis following long-haul flights: pilot study. Blood Coagul Fibrinolysis. 2002; 13(8): 755–757.
  103. Belcaro G, Cesarone MR, Shah SSG, et al. Prevention of edema, flight microangiopathy and venous thrombosis in long flights with elastic stockings. A randomized trial: The LONFLIT 4 Concorde Edema-SSL Study. Angiology. 2002; 53(6): 635–645.
  104. Cesarone MR, Belcaro G, Errichi BM, et al. The LONFLIT4--Concorde Deep Venous Thrombosis and Edema Study: prevention with travel stockings. Angiology. 2003; 54(2): 143–154.