Author(s): Nimia Reyes, Karon Abe

Deep vein thrombosis (DVT) is a condition in which a blood clot develops in the deep veins, usually in the lower extremities. A pulmonary embolism (PE) occurs when a part of the DVT clot breaks off and travels to the lungs, which can be life-threatening. Venous thromboembolism (VTE) refers to DVT, PE, or both. VTE is often recurrent and can lead to long-term complications (e.g., post-thrombotic syndrome after a DVT, chronic thromboembolic pulmonary hypertension after a PE).

Extended periods of limited mobility inherent to long-distance travel could increase a traveler’s risk for VTE. An association between VTE and air travel was first reported in the early 1950s; since then, long-distance air travel has become more common, leading to increased concerns about travel-related VTE.

Pathogenesis

Virchow’s classic triad for thrombus formation is venous stasis, vessel wall damage, and a hypercoagulable state. Prolonged, cramped sitting during long-distance travel interferes with venous flow in the legs, creating venous stasis. Seat-edge pressure to the popliteal area of the legs can aggravate venous stasis and contribute to vessel wall damage. Coagulation activation can result from an interaction between air cabin conditions (e.g., hypobaric hypoxia) and individual risk factors for VTE. Studies of the pathophysiologic mechanisms for the increased risk of VTE after long-distance travel have not produced consistent results, but venous stasis appears to play a major role. Other factors specific to air travel might increase coagulation activation, particularly in travelers with preexisting risk factors for VTE.

Incidence

The annual incidence of VTE in the general population is estimated to be 0.1% but is greater in subpopulations with risk factors for VTE (Box 8-03). The actual incidence of travel-related VTE is difficult to determine because there is no national surveillance for VTE and no consensus on the definition of travel-related VTE, particularly regarding duration of travel and period of observation after travel.

Air Travel–Related Venous Thromboembolism

Studies estimating the incidence of air travel–related VTE have used various criteria to determine risk factors and end points. For example, investigators have defined long-distance air travel as lasting anywhere from >3 hours to >10 hours. Although no standard definition exists, >4 hours is most often used. Post-flight observation period is similarly inconsistent and ranges from “hours after landing” to ≥8 weeks; 4 weeks, however, is most common. Finally, study outcomes range from asymptomatic DVT to symptomatic DVT/PE to severe or fatal PE. Asymptomatic DVT was estimated to be 5–20 times more common than symptomatic events, but asymptomatic DVT is of uncertain clinical significance and often resolves spontaneously.

In general, the incidence of air travel–related VTE appears to be low. For flights >4 hours, one study reported an absolute risk for VTE of 1 in 4,656 flights; another reported an absolute risk of 1 in 6,000 flights. People who travel on long-distance flights generally are healthier and therefore at a lower risk for VTE than the general population. Five prospective studies conducted to assess the incidence of DVT after travel >8 hours among travelers at low to intermediate risk for VTE yielded an overall VTE incidence of 0.5%; the incidence of symptomatic VTE was 0.3%.

Studies indicate that long-distance air travel might increase a person’s overall risk for VTE by 2- to 4-fold. Some studies found that long-distance air travel increased the risk of VTE occurring, while others either found no definitive evidence of increased risk, or found that risk increased only if ≥1 additional VTE risk factors were present. Level of risk correlates with duration of travel and with preexisting risk factors for VTE. Risk decreases with time after air travel and returns to baseline by 8 weeks; most air travel–related VTE occurs within the first 1–2 weeks after the flight.

A similar increase in risk for VTE is noted with other modes of long-distance travel (bus, car, train), which implies that increased risk is due mainly to prolonged limited mobility rather than by the air cabin environment.

Risk Factors

Most travel-related VTE occurs in travelers with preexisting risk factors for VTE (Box 8-03). The combination of air travel with preexisting individual risk factors might synergistically increase risk. Some studies have shown that 75%–99.5% of people who developed travel-related VTE had ≥1 preexisting risk factor; one study showed that 20% had ≥5 risk factors. For travelers without preexisting risk factors, the risk of travel-related VTE is low.

For air travelers, height appears to be an additional risk factor; people <1.6 m (5 ft, 3 in) and those >1.9 m (6 ft, 3 in) tall were at increased risk. Because airline seats are higher than car seats and cannot be adjusted to a person’s height, air travelers <1.6 m (5 ft, 3 in) tall might be more prone to seat-edge pressure to the popliteal area. Air travelers >1.9 m (6 ft, 3 in) tall are also at increased risk, possibly because taller travelers have less leg room.

Clinical Presentation

Signs and symptoms of DVT/PE are nonspecific. Typical signs or symptoms of DVT in the extremities include pain or tenderness, swelling, warmth in the affected area, and redness or discoloration of the overlying skin. The most common signs or symptoms of acute PE include unexplained shortness of breath, pleuritic chest pain, cough or hemoptysis, and syncope.

Diagnosis

Imaging studies are needed for diagnosis. Duplex ultrasonography is the standard imaging procedure for DVT diagnosis. Computed tomographic pulmonary angiography is the standard imaging procedure for diagnosis of PE. Ventilation-perfusion scan is the second-line imaging procedure.

Treatment

Anticoagulant medications commonly are used to treat DVT or PE; anticoagulants also are used for VTE prophylaxis. Bleeding can be a complication of anticoagulant therapy. The most frequently used injectable anticoagulants are unfractionated heparin, low molecular weight heparin (LMWH), and fondaparinux. Oral anticoagulants include apixaban, betrixaban, dabigatran, edoxaban, rivaroxaban, and warfarin.

Preventive Measures

The American College of Chest Physicians (ACCP) and the American Society of Hematology (ASH) each provide guidelines on the prevention of VTE in long-distance travelers.

American College of Chest Physicians Guidelines

ACCP 2012 guidelines (Grade 2C: weak recommendations, low- or very low-quality evidence): for long-distance travelers (>6 hours travel) at increased risk of VTE, the ACCP recommends frequent ambulation, calf muscle exercise, sitting in an aisle seat if feasible, and use of properly fitted below-the-knee graduated compression stockings (GCS) providing 15–30 mmHg of pressure at the ankle during travel. For long-distance travelers not at increased risk of VTE, use of GCS is not recommended. ACCP suggests against the use of aspirin or anticoagulants to prevent VTE in long-distance travelers.

American Society of Hematology Guidelines

ASH 2018 guidelines (conditional recommendations, very low certainty in the evidence of effects): for long-distance travelers (>4 hours travel) at substantially increased VTE risk (e.g., recent surgery, prior history of VTE, postpartum, active malignancy, or ≥2 risk factors, including combinations of the above with hormone replacement therapy, obesity, or pregnancy) the ASH guideline panel suggests GCS or prophylactic low molecular weight heparin (LMWH). If GCS or LMWH are not feasible, ASH suggests using aspirin rather than no VTE prophylaxis. For travelers without risk factors, ASH suggests not using GCS, LMWH, or aspirin for VTE prophylaxis.

Graduated Compression Stockings & Pharmacologic Prophylaxis

GCS appear to reduce asymptomatic DVT in travelers and are generally well tolerated. Decisions regarding use of pharmacologic prophylaxis for long-distance travelers at high risk should be made on an individual basis. When the potential benefits of pharmacologic prophylaxis outweigh the possible adverse effects, anticoagulants rather than antiplatelet drugs (e.g., aspirin) are recommended. People at increased risk should be evaluated with enough time before departure so that they understand how to take the medication; evaluate whether the traveler could have potential adverse effects from the combination of pharmacologic prophylaxis with any other medications they are taking.

Hydration

No evidence exists for an association between dehydration and travel-related VTE. Furthermore, no direct evidence exists to support the concept that drinking plenty of nonalcoholic beverages to ensure adequate hydration or avoiding alcoholic beverages has a protective effect. Therefore, maintaining hydration is reasonable and unlikely to cause harm, but it cannot be recommended specifically to prevent travel-related VTE.

In-Flight Mobility & Seat Assignment

Immobility while flying is a risk for VTE. Indirect evidence suggests that maintaining mobility could prevent VTE. In view of the role that venous stasis plays in the pathogenesis of travel-related VTE, recommending frequent ambulation and calf muscle exercises for long-distance travelers is reasonable.

An aisle seat also might be a protective factor to reduce the risk of developing VTE. In one study, travelers seated in window seats experienced a 2-fold increase in general risk for VTE compared with passengers in aisle seats; travelers with a body mass index ≥30 kg/m2 who sat in window seats had a 6-fold increase in risk. Conversely, aisle seats are reported to have a protective effect compared with window or middle seats, probably because travelers are freer to move around.

Recommendations

General protective measures for long-distance travelers include calf muscle exercises, frequent ambulation, and aisle seating when possible. Additional protective measures for long-distance travelers at increased risk of VTE include properly fitted below-the-knee GCS and anticoagulant prophylaxis, but only in particularly high-risk cases where the potential benefits outweigh the risks.