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      Deep venous thrombosis

      Latest update: - Authors: Matilde Hens, Nele Alders, Ula Maniewski

      Long-distance travel, whether by plane, car or bus increases the risk of venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE). The risk is elevated when the travel duration exceeds more than 4 hours, and further increases with longer travel times. The risk remains elevated for approximately 4 weeks after the journey. Prolonged immobility, resulting in venous stasis, is considered the primary causative factor. 

      Even with an increased risk, the absolute risk for the average traveller remains relatively low. Estimates of the absoluterisk of a symptomatic DVT in the weeks following a flight of more than 4 hours range from 1/4600 to 27/1.000.000 travellers. The risk for a severe pulmonary embolism is even lower. 

      However, when travellers have other risk factors (e.g. a history of VTE, recent surgery, active cancer, limited mobility, pregnancy, oestrogen use, obesity, blood clotting disorders or older age) the risk of travel related VTE increases. It's worth noting that when multiple risk factors are present, they may reinforce each other, as shown in some studies

      Symptoms

      Symptoms of a DVT include swelling, redness and pain in the affected leg. The symptoms of pulmonary embolism include sudden shortness of breath, chest pain, tachycardia, dizziness, loss of consciousness and anxiety.

      Prevention

      Prevention strategies can be divided into 4 groups: 

      • awareness of VTE as a disease and information on signs/symptoms
      • general measures
      • compression stockings
      • pharmacological prophylaxis

      Awareness

      All travellers should be aware of the signs and symptoms of DVT and PE and should be advised to seek immediate medical attention if they experience any of these symptoms.

      General measures

      All travellers, including those using other preventive measures (such as anticoagulants or compression stockings), should be advised to follow to the subsequent general measures:

      • Standing up and walking around regularly (every 1 to 2 hours). A seat next to the aisle can facilitate this. 
      • Additionally, exercise can be done to activate the calf muscles by flexing and extending the knees and ankles.
      • Avoid the use of alcohol and sleeping medication
      • Maintain adequate hydration.
      • Wear loose and comfortable clothing.

      These measures have not been formally studied, but they do not have any negative effects or costs.

      Compression stockings

      The use of compression stockings reduces the incidence of asymptomatic VTE, but their effect on preventing symptomatic DVT, PE or death in travellers could not be assessed. No serious adverse effects were reported in association with the use of compression stockings, and they were well tolerated. Furthermore, the use of compression stockings can increase the traveller's awareness and they can potentially reduce oedema.

      Compression stockings may be particularly useful for travellers at substantially increased risk for VTE, who are not using anticoagulants. This includes people who are travelling for more than 4 hours, with:

      • one of the following risk factors:
        • major surgery in the last 6 weeks
        • active malignancy
        • postpartum women (up to 6 weeks postpartum)
        • immobile patients
        • previous history of VTE: if pharmacological prophylaxis is not possible
      • OR 2 or more of the following risk factors:
        • oestrogen use (oral hormone replacement therapy or combined oral contraception)
        • obesity (BMI > 30kg/m2)
        • pregnancy 
        • low-risk hereditary thrombophilia (e.g., heterozygote factor V Leiden, heterozygote prothrombin gene mutations, Protein C and Protein S deficiencies) without previous history of VTE
        • age > 60y
        • large varicose veins
        • clinical cardiovascular disease (e.g., coronary heart disease, heart failure, peripheral artery disease, …) 

      Compression stockings should be used in addition to the general measures described above.

      Below knee graduated compression stockings with a pressure of 15-30 mmHg at the ankle are recommended. These stockings do not need to be custom-made and can be purchased without a prescription, for example at orthopaedic stores, pharmacies, or medical equipment shops.

      Pharmacological prophylaxis

      Data on the efficacy of anticoagulants in VTE prevention in travellers is limited, but there is there is substantial evidence supporting their efficacy in primary and secondary prevention for other indications. The risk of major bleeding with preventive doses of low molecular weight heparins (LMWHs) or preventive doses of direct oral anticoagulants (DOACs) is low. However, the specific risk-benefit ratio for travellers is unknown.

      Prophylactic use of anticoagulants can be considered for the following travellers, provided that the risk of bleeding does not outweigh the risk for thrombosis:

      • Travellers who have a personal history of VTE.
      • Other travellers who are at substantially increased risk due to the presence of multiple of the above-mentioned risk factors, where the use of compression stockings is not feasible.

      For the prevention of VTE in travellers, both DOACs and LMWH can be used. Factors to consider when selecting the best option for the patient include patient convenience (oral intake versus injection), costs and the presence of a contraindication to a particular drug.

      Examples of anticoagulants that can be used for VTE prevention in travellers:

      • rivaroxaban (Xarelto®, PO): single dose of 10mg 1-2 hours before departure
      • apixaban (Eliquis®,PO): single dose of 5 mg 1-2 hours before departure
      • enoxaparin (Clexane®,SC): single injection of 40mg 2-4 hours before departure
      • nadroparin (Fraxiparine®,SC): single injection of 3,800 IU for people under 70kg or 5,700 IU for people over 70kg - 2-4 hours before departure.

      For trips exceeding 24 hours, intake or injection should be administered every 24 hours.

      The prophylactic use of acetylsalicylic acid (aspirin) is not recommended. In general, they are effective in preventing arterial thrombotic events but their effectiveness in VTE prevention has not been proven.There are no data in travellers and in other populations. Compared to anticoagulation therapy (e.g., DOAC’s) its effectiveness is inferior, with similar bleeding risks.

      Reference

      Clarke, M. J., Broderick, C., Hopewell, S., Juszczak, E., & Eisinga, A. (2021). Compression stockings for preventing deep vein thrombosis in airline passengers. Cochrane Database of Systematic Reviews, 2021(4). 

      Schünemann, H. J., Cushman, M., Burnett, A. E., Kahn, S. R., Beyer-Westendorf, J., Spencer, F. A., Rezende, S. M., Zakai, N. A., Bauer, K. A., Dentali, F., Lansing, J., Balduzzi, S., Darzi, A., Morgano, G. P., Neumann, I., Nieuwlaat, R., Yepes-Nuñez, J. J., Zhang, Y., & Wiercioch, W. (2018). American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Advances, 2(22), 3198–3225. 

      Cesarone, M. R., Belcaro, G., Nicolaides, A. N., Incandela, L., De Sanctis, M. T., Geroulakos, G., Lennox, A., Myers, K. A., Moia, M., Ippolito, E., & Winford, M. (2002). 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, 53(1), 1–6. 

      Chandra, D., Parisini, E., & Mozaffarian, D. (2009). Meta-analysis: travel and risk for venous thromboembolism. Annals of Internal Medicine, 151(3), 180–190. 

      Kuipers, S., Venemans, A., Middeldorp, S., Büller, H. R., Cannegieter, S. C., & Rosendaal, F. R. (2014). The risk of venous thrombosis after air travel: Contribution of clinical risk factors. British Journal of Haematology, 165(3), 412–413. 

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