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 pulmonary embolism occurs when a part of the clot breaks off and travels to the lungs, a potential life threat. 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.
Extended periods of limited mobility inherent to long-haul travel may increase a travelers’ risk for DVT/PE; an association between VTE and air travel was first reported in the early 1950s. Since then, as prolonged air travel has become more common (>300 million people take long-distance flights each year) concerns about travel-related VTE have become more prevalent.
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 as well as contribute to vessel wall damage. 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. Coagulation activation may result from an interaction between cabin conditions (such as hypobaric hypoxia) and individual risk factors for VTE.
There is no national surveillance for VTE; research estimates the annual incidence of VTE in the general population at 0.1% although it is higher in subpopulations with risk factors (Box 8-1). In the absence of national surveillance for VTE (as a whole), the incidence of travel-related VTE is even more difficult to determine and varies from study to study. Complicating the matter, no consensus exists on what constitutes a travel-related VTE, particularly duration of travel and period of observation after travel.
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 at lower risk for VTE than the general population. Five prospective studies to assess 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%.
Association with Travel
Studies examining the association between long-range travel, particularly air travel, and VTE do not share common definitions. Flight duration, used both as the criteria for what constitutes long-range travel as well as a surrogate (albeit imprecise) measure of the length of time travelers are immobile, ranges from >3 hours to >10 hours. Duration of observation of travelers after flights also varies, ranging from a few hours after landing to ≥8 weeks posttravel. Furthermore, outcome measures differ—from asymptomatic DVT to symptomatic DVT/PE to severe or fatal PE.
In aggregate, the studies indicate that long-distance air travel may increase the risk for VTE by 2- to 4-fold; however, some studies found that long-distance travel increased the risk for VTE, while others found no definitive evidence of an increase in risk, perhaps because of the aforementioned differences in definitions used. Still others identified an increase in risk only if ≥1 additional risk factor was present. Asymptomatic DVT (which is of uncertain clinical significance and often resolves spontaneously) was estimated to be 5- to 20-fold more common than symptomatic events.
A similar increase in risk for VTE is seen with other modes of long-distance travel (car, bus, or train). This implies that the increase in risk is due mainly to prolonged limited mobility rather than by the air cabin environment, per se. 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.
Box 8-1. 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
Most travel-related VTE occurs in travelers with preexisting risk factors for VTE (Box 8-1). The combination of air travel with preexisting individual risk factors may synergistically increase risk. Some studies have shown that 75%–99.5% of those who developed travel-related VTE had ≥1 preexisting risk factor(s); 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 airline passengers, risk of travel-related VTE varies depending on traveler height, with the lowest risk among adults of average height and the greatest risk among adults at both extremes. Because of the inability to adjust airline seats, adults <1.6 m (5 ft 3 in) may be more prone to pressure to the popliteal area, a phenomenon already identified as contributing to venous stasis in the legs and possibly vessel wall damage. Air travelers >1.9 m (6 ft 3 in) are also at increased risk for VTE, possibly because in the main cabin, in particular, there is typically less leg room for taller travelers.
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 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.
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.
Preventive Measures for Long-Distance Travelers
The American College of Chest Physicians published the 9th edition of their Antithrombotic Therapy and Prevention of Thrombosis EvidenceBased 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 8-1), 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 8-1), use of properly fitted, below-knee graduated compression stockings (GCS) providing 15–30 mm Hg of pressure at the ankle during travel is suggested. GCS appear to reduce asymptomatic DVT in travelers and are well tolerated, generally. For long-distance travelers not at increased risk of VTE, use of GCS is not recommended.
The guidelines do not recommend the use of aspirin or anticoagulants globally to prevent VTE in long-distance travelers. Decisions regarding use of pharmacologic prophylaxis for long-distance travelers at particularly high risk should be made 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. Patients at increased risk should be evaluated with enough time before departure so that they 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.
There is no evidence of 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, while maintaining hydration is reasonable and unlikely to cause harm, it cannot be recommended specifically to prevent travel-related VTE.
Immobility while flying is a risk for VTE. Indirect evidence suggests that maintaining mobility may prevent VTE. In view of the role that venous stasis plays in the pathogenesis of travel-related VTE, it would be reasonable to recommend frequent ambulation and calf muscle exercises for long-distance travelers.
Seat location within an aisle may also be a protective factor to reduce the risk of developing VTE. In one study, travelers seated in window seats, as compared to those in aisle seats, experienced an increase in the general risk of VTE by 2-fold; obese travelers 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.
- 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