What is the Risk of VTE On a Long Haul Flight?

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We are a global society, and long distance travel is a routine part of life for many of us, our colleagues, and our patients. For some, long distance travel by any modality that involves long periods of stationary positioning (i.e. car, plane, bus, train) carries the unfortunate risk of developing venous thromboembolism (VTE). Though the risk is small, evidence tells us that travel for longer periods of time and certain risk factors increases the likelihood of VTE. The exact pathogenesis for thrombosis with extended travel is unclear. Likely contributing factors include venous stasis due to prolonged immobility and activation of coagulation factors II, VIII, IX, and fibrinogen [1].

Dehydration is also commonly thought to elevate risk and promote coagulopathy, though there is no definitive scientific evidence to support this.

The Risk
Overall, the risk of developing VTE from long term travel is low. Air travel longer than eight hours leads to a two-fold increased risk of VTE over flights shorter than four hours in duration [2]. The risk is also greatest within the first two weeks following long-term travel and returns to baseline by eight weeks after travel. One meta-analysis of 14 studies found that the overall pooled risk for VTE in travelers, compared with non-travelers, was 2.8 (95% CI 2.2-3.7) [3]. Most people who develop travel-related VTE have one or more pre-existing risk factors, though idiopathic cases are sporadically reported. Risk factors include: age > 40, genetic or acquired thrombophilia, women who are pregnant or taking any estrogen containing compounds, obesity, history of prior VTE, recent major surgery or trauma (within three months), varicose veins in the legs, active malignancy, limited mobility, and possibly window seating on aircraft [4-6].

Prevention
The American College of Chest Physician (ACCP) 2012 guidelines provides detailed recommendations for VTE prophylaxis in long-distance travelers [6]. General prophylaxis measures for travel-related VTE have not been formally studied, but evidence-based guidelines and expert clinicians routinely recommend their use. Preventive measures that should be employed by all travelers include avoidance of dehydration and excessive alcohol and caffeine consumption, wearing loose fitting clothing, sitting with legs uncrossed, and periodic ambulation every 1-2 hours for the duration of travel. For long-distance travelers at increased risk of VTE based on the risk factors above, frequent calf muscle stretching via flexion and extension of the ankles, bending of the knees and sliding the legs back and forth to promote thigh muscle stretching, and walking whenever possible is beneficial. For air travel, aisle seating or seating in areas with additional leg room is recommended when feasible. Individuals at increased risk of VTE also benefit from wearing properly fitted below-knee graduated compression stockings that provide 15-30 mm Hg pressure at the ankle [5,6].

Pharmacologic Prophylaxis
The ACCP 2012 guidelines recommend against the routine use of aspirin of blood thinners to prevent travel-related thrombosis; thus pharmacologic thromboprophylaxis is not necessary for most travelers. If individuals are considered at particularly high risk of travel-related VTE due to significant thrombophilia, prior VTE events (including travel-related), or multiple risk factors listed above, pharmacologic prophylaxis may be warranted on an individual basis if potential benefit exceeds the risk of bleeding or other adverse events. There is a lack of data regarding efficacy, safety, or comparative effectiveness of prophylactic anticoagulants during travel. Historically, prophylaxis 1-2 hours prior to travel with subcutaneous injectable anticoagulants, such as enoxaparin has been the standard recommendation. Small studies and case reports have shown both enoxaparin 40mg and fondaparinux 2.5mg injections to be effective, though neither is FDA approved for this indication. Many individuals are uncomfortable with injections, and they may be cost prohibitive and less ideal for some travel situations. Though they are also not FDA approved for this indication, there are some oral anticoagulants that may be an attractive alternative. Oral Factor Xa inhibitors, such as a single dose of rivaroxaban 10mg 2 hours prior to travel should provide adequate prophylactic protection, and offer the advantage of reduced cost and tablet dosage form. Warfarin should not be initiated for travel prophylaxis, as it is not possible to attain therapeutic anticoagulation with a single oral dose. Aspirin has not been shown to confer any prophylactic benefit during travel, and as such, should not be administered as monotherapy or as an adjunct to augment the effects of other anticoagulants. It should also be noted that In travelers who are already receiving therapeutic anticoagulation regardless of the indication, no additional prophylaxis is warranted [5,6]. As always, patients should be involved in discussion and education surrounding the risk vs. benefit of anticoagulant prophylaxis prior to initiation of therapy.


REFERENCES

  1. Schreijer AJ, Hoylaerts MF, Meijers JC, et al. Explanations for coagulation activation after air travel. J Thromb Haemost 2010; 8:971.
  2. MacCallum PK, Ashby D, Hennessy EM, et al. Cumulative flying time and risk of venous thromboembolism. Br J Haematol 2011; 155:613
  3. Chandra D, Parisini E, Mozaffarian D. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med 2009; 151:180.
  4. Schreijer AJ, Cannegieter SC, Doggen CJ, Rosendaal FR. The effect of flight-related behaviour on the risk of venous thrombosis after air travel. Br J Haematol 2009; 144:425.
  5. Gavish I et al. Air travel and the risk of thromboembolism. Intern Emerg Med 2011;6:113-116.
  6. Kahn SR et al. Prevention of VTE in non-surgical patients: Antithrombotic therapy and prevention of thrombosis. 9th ed: ACCP evidence based clinical practice guidelines. Chest Feb 2012;141:2supple195S-e226S.

ABOUT THE AUTHOR

Dr. Hatfield is a Lead Clinical Pharmacist Specialist, Emergency Medicine, at UNC Healthcare. She is an assistant professor of clinical education at UNC Eshelman School of Pharmacy.

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