Deep Vein Thrombosis & Pulmonary Embolism
Deep vein thrombosis (DVT) is a condition in which a blood clot develops in the deep veins, most commonly in the lower extremities. A part of the clot can break off and travel to the lungs, causing a pulmonary embolism (PE), which can be life threatening. Venous thromboembolism (VTE) refers to DVT, PE, or both. VTE is often recurrent, and long-term complications, such as postthrombotic syndrome after a DVT or chronic thromboembolic pulmonary hypertension after a PE, are frequent.
People traveling for extended periods of time may be at increased risk for DVT/PE because they have prolonged limited mobility. More than 300 million people travel on long-distance flights each year. An association between VTE and air travel was first reported in the early 1950s, and since then, long-distance air travel has become more common, leading to increased concerns about travel-related VTE.
Virchow’s classic triad for thrombus formation is venous stasis, vessel wall damage, and the hypercoagulable state. Prolonged cramped sitting during long-distance travel interferes with venous flow in the legs and causes venous stasis. Seat-edge pressure on the popliteal area may contribute to vessel wall damage as well as venous stasis. Coagulation activation may result from an interaction between cabin conditions (such as 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 may increase coagulation activation, particularly in travelers with preexisting risk factors for VTE.
The annual incidence of VTE in the general population has been estimated at 0.1% but is higher in subpopulations with risk factors for VTE (Box 2-10). The actual incidence of travel-related VTE is difficult to determine, since there is no national surveillance for VTE and no consensus on the definition of travel-related VTE, particularly in regard to duration of travel and period of observation after travel. Estimates of travel-related VTE incidence vary because of differences between studies in duration of travel, measured outcome, period of observation after the flight, and the populations observed.
In general, the overall incidence of travel-related VTE is low. Two studies reported that the absolute risk of VTE for flights >4 hours is 1 in 4,656 flights and 1 in 6,000 flights. People who travel on long-distance flights are generally healthier and therefore are at lower risk for VTE than the general population. Five prospective studies that assessed the incidence of DVT among travelers at low to intermediate risk for VTE after travel >8 hours yielded an overall incidence of VTE of 0.5%, while the incidence of symptomatic VTE was 0.3%.
Box 2-10. Venous thromboembolism (VTE) risk factors
General risk factors for VTE include the following:
- Older age (increasing risk after age 40)
- Obesity (BMI ≥30 kg/m2)
- Estrogen use (hormonal contraceptives or hormone replacement therapy)
- Pregnancy and the postpartum period
- Thrombophilia (such as factor V Leiden mutation or antiphospholipid syndrome) or a family history of VTE
- Previous VTE
- Active cancer
- Serious medical illness (such as congestive heart failure or inflammatory bowel disease)
- Recent surgery, hospitalization, or trauma
- Limited mobility
Association with Travel
Numerous studies have examined the association between travel, particularly air travel, and VTE with varying results due to differing study methods. Outcomes ranged from asymptomatic DVT to symptomatic DVT/PE and to severe or fatal PE. Asymptomatic DVT is estimated to be 5- to 20-fold more common than symptomatic events, is of uncertain clinical significance, and often resolves spontaneously. Definitions of long-distance travel ranged from flight duration >3 hours to >10 hours (most >4 hours). The period of observation after the flight ranged from hours after landing to ≥8 weeks (most 4 weeks).
Overall, these studies indicate that long-distance air travel may increase a person’s risk for VTE by 2- to 4-fold. However, published results from these studies vary; some studies found that long-distance travel increased the risk of VTE, and others either found no definitive evidence that it increased the risk of VTE or found that it increased the risk only if ≥1 additional risk factors were present.
A similar increase in risk is also seen with other modes of travel, such as car, bus, or train, implying that the increase in risk is caused mainly by prolonged limited mobility rather than by the cabin environment. The risk is the same for economy-class and business-class travel. The risk increases with increasing travel duration and with preexisting risk factors for VTE. The 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.
Most travel-related VTE occurs in travelers with preexisting risk factors for VTE (Box 2-10). The combination of air travel with preexisting individual risk factors may have a synergistic effect on the risk for VTE. Some studies have shown that 75%–99.5% of those 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. However, a person may not be aware that he or she has a risk factor such as inherited thrombophilia.
For air travelers, height appears to be an additional risk factor. Risk of travel-related VTE increases with height <1.6 m (5 ft, 3 in). Airplane seats are higher than car seats and cannot be adjusted to a person’s height; therefore, shorter people who travel by air may experience seat-edge pressure to the popliteal area. Risk of travel-related VTE also increases with height >1.9 m (6 ft, 3 in), possibly because taller travelers have less leg room.
Signs and symptoms of DVT/PE are nonspecific:
- Typical signs or symptoms of DVT in the extremities include pain or tenderness, swelling, increased 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.
Imaging studies are needed for diagnosis:
- Duplex ultrasonography is the standard imaging procedure for diagnosis of DVT.
- Computed tomographic pulmonary angiography is the standard imaging procedure for diagnosis of PE. Ventilation-perfusion scan is the second-line imaging procedure.
Anticoagulants are the medications most commonly used to treat DVT or PE. 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 warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban.
It is critical that patients who are at increased risk be evaluated with enough time prior to departure so that travelers understand how to take the medication and the health provider can evaluate whether there are any potential adverse effects of the combination of these medications with others that the travel health provider has prescribed.
Preventive Measures for Long-Distance Travelers
The American College of Chest Physicians published the 9th edition of their Antithrombotic Therapy and Prevention of Thrombosis Evidence-Based Clinical Practice Guidelines in February 2012. Recommendations for long-distance travelers (considered grade 2C: weak recommendation, low- or very low-quality evidence) are the following:
- For long-distance travelers at increased risk of VTE (Box 2-10), frequent ambulation, calf muscle exercise, and sitting in an aisle seat if feasible are suggested.
- For long-distance travelers at increased risk of VTE (Box 2-10), use of properly fitted, below-knee graduated compression stockings (GCS) providing 15–30 mm Hg of pressure at the ankle during travel is suggested. For all other long-distance travelers, use of GCS is not recommended.
- For long-distance travelers, the use of aspirin or anticoagulants to prevent VTE is not recommended.
There is no evidence for an association between dehydration and travel-related VTE and no direct evidence that drinking plenty of nonalcoholic beverages to ensure adequate hydration or avoiding alcoholic beverages has a protective effect. Therefore, while maintaining hydration is reasonable and unlikely to cause harm, it cannot be recommended specifically to prevent travel-related VTE.
There is evidence that immobility while flying is a risk for VTE and indirect evidence that maintaining mobility may prevent VTE. In view of the role of venous stasis in the pathogenesis of travel-related VTE, it would be reasonable to recommend frequent ambulation and calf muscle exercises for long-distance travelers.
Compared with aisle seats, window seats in one study were reported to increase the general risk of VTE by 2-fold, while obese travelers had a 6-fold increase in risk. Aisle seats are reported to have a protective effect, compared with window or middle seats, probably because travelers are freer to move around.
GCS are indicated for long-distance travelers at increased risk. GCS appear to reduce asymptomatic DVT in travelers and are generally well tolerated.
Global use of anticoagulants for long-distance travel is not indicated. Pharmacologic prophylaxis for long-distance travelers at particularly high risk should be decided on an individual basis. In cases where the potential benefits of pharmacologic prophylaxis outweigh the possible adverse effects, anticoagulants rather than antiplatelet drugs (such as aspirin) are recommended.
- General measures for long-distance travelers:
- Calf muscle exercises
- Frequent ambulation
- Aisle seating when feasible
- Additional measures for long-distance travelers at increased risk of VTE:
- Properly fitted below-knee GCS
- Anticoagulant prophylaxis only in particularly high-risk cases where the potential benefits outweigh the risks
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Nimia L. Reyes, Michele G. Beckman, Karon Abe