Travel-Associated Venous Thromboembolism

Abstract

Introduction—

Long-distance travel is assumed to be a risk factor for venous thromboembolism (VTE). However, the available data have not clearly demonstrated the strength of this relationship, nor have they shown evidence for the role of thromboprophylaxis.

Methods—

We performed a systematic review of the literature. We also summarized available guidelines from 5 groups.

Results—

We found 18 studies that addressed this question. Based on the data presented in the review, we conclude that there is an association between VTE and length of travel, but this association is mild to moderate in effect size with odds ratios between 1.1 and 4. A dose-response relationship between VTE and travel time was identified, with a 26% higher risk for every 2 h of air travel (P=0.005) starting after 4 h. The quality of evidence for both travel length and thromboprophylaxis was low. However, low-risk prophylactic measures such as graduated compression stockings were shown to be effective in VTE prevention. There is heterogeneity among the different practice guidelines. The guidelines generally concur that no prophylaxis is necessary in travelers without known thrombosis risk factors and advocate for conservative treatment such as compression stockings over pharmacologic prophylaxis.

Conclusions—

We conclude air travel is a risk factor for VTE and that there is a dose relationship starting at 4 h. For patients with risk factors, graduated compression stockings are effective prophylaxis.

Introduction

Venous thromboembolism (VTE) is a common and sometimes lethal disease. In the United States, the incidence is as high as 900,000 people per year, with 60,000 to 100,000 deaths per year.¹ Risk stratification and disease prevention are especially critical, as sudden death occurs in nearly 25% of patients with pulmonary embolisms (PE).¹ Known VTE risk factors include immobilization, recent surgery, pregnancy, oral contraceptive use, malignancy, and inherited thrombophilias.²

An association between extended travel and VTE was first documented in the 1950s,³ and this relationship continues to be observed. The link was considered so strong that travel-associated VTE was nicknamed “economy class syndrome” in the 1970s.⁴ Further studies expanded this relationship to not just air travel, but to any mode of travel.⁵ Pathophysiologic mechanisms have been explored, many centering on the role of immobilization, but none have proven the link between travel and VTE.

Despite the common notion that travel and VTE risk are definitively linked, the data are unclear as to the magnitude of this risk, the association between duration or type of travel and VTE risk, and the role of prophylaxis in mitigating this risk. We performed a systematic review of the literature to provide clarity to practitioners. Finally, we reviewed current major guidelines on travel-associated VTE to supplement these findings.

Methods

A systematic literature search was conducted to locate studies addressing the risk of VTE based on travel length and the role of thromboprophylaxis in reducing VTE risk. The specific questions were as follows: In adults traveling by plane, train, or automobile, does the risk of thrombosis increase with the length of travel; and in adults traveling by plane, train, or automobile, does the use of thromboprophylaxis decrease the risk of deep vein thrombosis (DVT)/VTE? The search included comparative studies, controlled clinical trials, evaluation studies, guidelines, meta-analyses, randomized clinical trials, or systematic reviews.

The inclusion criteria were comparative studies, controlled clinical trials, evaluation studies, guidelines, meta-analysis, randomized clinical trials, or systematic reviews in the English language published since 2007. We searched Ovid MEDLINE for relevant studies published in the English language since 1946, which resulted in over 500 articles relating to VTE risk and prophylaxis in travelers, 18 of which met the inclusion criteria that allow comparisons of travel length as a thrombosis risk factors and studies/meta-analysis of prophylaxis. Studies analyzed in systemic reviews are not separately mentioned. Two authors (TK, AH) independently evaluated the studies for relevance and quality. Discussion of analysis of individual studies cites original authors’ own conclusions and not reanalysis of data by the authors. External guidelines on VTE management in travelers were also identified.

Results

RISK OF VTE BASED ON TRAVEL LENGTH

Our search yielded 4 systematic reviews and 6 nonrandomized studies. One of the systematic reviews also performed 2 meta-analyses, one of air travel alone and the other of all types of transport.⁶ Table 1 summarizes the main characteristics of these studies. The studies show an increase in VTE risk with travel, with odds ratios (OR) ranging from 1.1 to 4.0.^2,6,7 Increasing duration of travel was also found to be significantly associated with VTE in 2 studies.^7,8

Table 1.

Studies assessing risk of venous thromboembolism based on travel length

Author; year published; study type; n	Patient population or studies analyzed	Study intervention/comparator	Endpoint results/Outcome	Study limitations
Beam et al (2009); prospective; cohort study; n=794010	Patients with suspected PE	Intervention: Recorded 1 of 6 types of immobility: no immobility, general or whole-body immobility >48 h, limb (orthopedic) immobility, travel >8 h causing immobility within the previous 7 d, neurologic paralysis, or other immobility not listed above.	Risk of VTE was substantially increased by presence of limb, whole-body, or neurologic immobility but not by travel greater than 8 h (travel OR=1.19; 95% CI, 0.85–1.67).	None
Chandra et al (2009); systematic review with meta-analysis; 14 studies with n=40557	Reports investigating association between travel and VTE for persons who used any mode of transportation and if nontraveling persons were included for comparison	Intervention: Patients traveling at least 3 h (11 studies), with 3 studies with no limitation or not reporting travel time. Comparator: Nontravelers	Overall pooled RR for VTE in travelers: 2.0 (95% CI, 1.5–2.7); after exclusion of studies with referred controls: pooled RR: 2.8 (CI, 2.2–3.7), without significant heterogeneity; 18% higher risk for VTE for each 2-h increase in duration of travel by any mode (P=0.010) and a 26% higher risk for every 2 h of air travel (P=0.005).	Methods and/or results were inconsistent across studies.
Kuipers et al (2007); systematic review; 55 studies2	Studies of air travel with VTE	Intervention: Case-Control studies (n=10): travel frequency of cases of symptomatic VTE. Observational follow-up studies (n=14): travelers screened for VTE. RCTs (n=11): assessed the effect of various prophylactic measures on the risk of VTE after air travel. Pathophysiological studies (n=14): Studies looked at what factors and mechanisms increase the risk of VTE after air travel.	Case-Control studies: Pooled OR=1.7 (95% CI, 1.4–2.1) Flights >8 h: pooled OR=3.9 (95% CI, 1.4–10.7) Observational follow-up studies: absolute risk of a symptomatic event within 4 wk of flights >4 h: 1/4600 flights. Risk of severe PE immediately after travel: 4.8 per million in flights longer than 12 h. RCTs: Due to high risk of bias among studies, the results were not discussed in the systematic review. Pathophysiological studies: Insufficient data and excessive variability to draw conclusions.	Quality of studies was not appraised or studies were low quality. Methods and/or results were inconsistent across studies.
Kuipers et al (2014); prospective cohort study; n=263022	All pilots who were members of the Dutch pilot union between 1993–2003	Intervention: Pilots questioned for the occurrence of VTE, presence of risk factors for VTE, and number of flight hours per year and rank. Comparator: General Dutch population and a population of frequently flying employees of multinational organizations.	Six VTEs were reported, yielding an incidence rate of 0.3 per 1000 person-years. Standardized morbidity ratios comparing pilots to other populations: 0.8 (general population), 0.7 (all employees), 0.6 (frequently traveling employees). The incidence rate did not increase with number of flight hours per year and did not clearly vary by rank.	Failure to adequately control confounding. Differences in important prognostic factors at baseline.
MacCallum et al (2011); case-control; n=550 cases and 1971 controls23	Adults with confirmed VTE on anticoagulants, with sex-matched controls	Intervention: Questionnaire to ascertain basic demographic characteristics, history of VTE, air travel within the past 2 y, and surgery within the past 2 y.	Cumulative flying time >12 h within the previous 4 weeks: OR=2.75 (95% CI, 1.44–5.28). Flying time >4 h in a single leg in the previous 4 weeks: OR=2.20 (95% CI, 1.29–3.73). These risks were no longer evident by 12 wk and were similar to those of day-case or minor surgery (OR=5.35; 95% CI, 2.15–13.33).	Differences in important prognostic factors at baseline.
Philbrick et al (2007); systematic review; 25 studies8	Primary data concerning the risk of travel for VTE or tested preventive measures for travel-related VTE	Intervention: Risk of travel-related VTE (6 case-control studies, 10 cohort studies).	Results: Duration of travel (<6 h compared to 6–8 h, OR=0.01) and clinical risk (“higher” risk travelers compared to “lower,” OR 3.6) were significantly related to VTE rate.	Quality of studies was not appraised or studies were low quality.
Pietrzyk (2016); retrospective chart analysis; n=200724	Adult patients on passenger vessel who presented with suspicion of DVT after air flight >8 h	Intervention: In patients with possible DVT, Wells score, lower extremity ultrasound, and D-dimer were performed. Comparator: passengers without DVTs	Results: The study showed 3 (0.15%) patients with possible DVT (based on Wells score) of a total of 2007 passengers who have completed a flight >8 h, of whom only 2 (0.1%) had positive ultrasound and D-dimer findings.	Failure to adequately control confounding. Differences in important prognostic factors at baseline.
Schreijer et al (2009); case-control; n=11,03321	Consecutive patients ages 18–70 y with first episode of VTE	Intervention: Flight >4 h less than 9 wk prior to date of VTE Comparator: Patient partners	Results: Window seating compared to aisle seating increased the risk twofold (OR=2.2; 95% CI, 1.1–4.4). The risk was not affected by alcohol consumption (OR=1.1; 95% CI, 0.5–2.4). Flying business class may lower the risk but is not significant (OR 0.7; 95% CI, 0.2–1.8).	None
Trujillo-Santos et al (2008); systematic review; 9 studies6	Case-control studies, no language or publication date restriction	Intervention: Calculated ORs with 95% CIs for each study	Results: OR varied between 1.1 and 4.0 The studies were highly heterogeneous in methodology. Meta-analysis: plane travel only (OR=1.21; 95% CI, 0.95–1.55); all types of transport, (OR=1.46; 95% CI, 1.24–1.72).	Quality of studies was not appraised or studies were low quality. Methods and/or results were inconsistent across studies.
Lehmann et al (2009); retrospective chart review; n=578	Patients with acute PE Exclusion criteria: Secondary PE after admission or admission based on a non-PE primary diagnosis	Intervention: All travel-associated PE cases, independent from the mode of transportation, were combined under economy-class syndrome. This definition includes PE due to prolonged sitting in a plane, bus, train, or car, and 1 patient in a simulation. Furthermore, they distinguished between air-travel economy-class syndrome and non-air-travel economy-class syndrome.	In general, economy-class syndrome was a rare event (1 event/5 million passengers), where long-haul flights over 5000 km lead to a 17-fold risk increase compared with shorter flights.	Failure to adequately control confounding.

OR, odds ratio; PE, pulmonary embolism; RCT, randomized control trial; RR, relative risk; VTE, venous thromboembolism.

One review, including 14 studies totaling over 4000 cases of VTE, found that the overall pooled relative risk (RR) for VTE in travelers was 2.0 (95% CI, 1.5–2.7).⁷ Further analysis of a dose-response relationship between travel and VTE found an 18% higher risk for VTE for each 2-h increase in duration of travel by any mode (P=0.010) and a 26% higher risk for every 2 h of air travel (P=0.005).⁷ Another review also examined duration of travel and found that both duration (<6 h compared to 6–8 h: OR 0.011) and clinical risk were significantly related to VTE rate.⁸

A 2007 systemic review examined 55 studies, including case-controlled studies, observational studies, and randomized controlled trials. Analysis of 3 of those case-controlled studies showed a pooled OR for flights over 8 h of 3.9 (95% CI, 1.4–10.7). Two of the observational studies found an absolute risk for symptomatic VTE within 4 wk of flights greater than 4 h as 1/4600 flights. Further, the risk of severe PE occurring immediately after air travel increased with duration of flight, from 0 events in flights <3 h to 4.8 per 1 million persons in flights >12 h.²

A review of 8 case-controlled studies found that the OR between long travel time and VTE varied from 1.1 to 4.0, which was significant in only 4 out of the 9 studies.⁶ Of the 2 meta-analyses completed in this paper, 1 analysis focused on travel by plane, finding the relationship between long travel time and VTE was not significant (OR=1.21; 95% CI, 0.95–1.55). The second meta-analysis focused on all types of transport and reported a slightly higher clinical significance (OR=1.46; 95% CI, 1.24–1.72). A study limited to pulmonary embolisms noted a 17-fold increase in risk with flight distances over 5000 km (>6 h).⁹

Overall, the available research suggests there is thrombotic risk of travel and this does increase with increasing lengths of travel. However, absolute risks remain low with a low quality of evidence. Odds ratios from the systematic reviews show a mild effect size with high variability among reviews. Some studies show no significantly increased association at all.^6,10 Furthermore, the quality of available evidence is low due to study inconsistency as noted in Table 1. In some studies, the risk with very short travel (<4 h) appears to be lower than in controls. This was believed to be due to the “healthy traveler” effect that assumes that people who are traveling have fewer risk factors for thrombosis than controls.¹¹ In the systematic reviews, the limitations were primarily due to low or unexamined study quality, or inconsistent methods and results across studies. In the nonrandomized studies, primary limitations were inadequate control of confounding and difference in prognostic indicators at baseline. Individual study limitations are listed in Table 1.

EFFICACY OF THROMBOPROPHYLAXIS

Our search yielded 3 systematic reviews and 3 nonrandomized studies. Table 2 summarizes the main characteristics of these studies. Two of the systematic reviews also addressed length of travel and VTE risk,^2,8 while 1 addressed solely the effect of compression stockings on flights lasting at least 4 h and included 10 studies.^2,8,12 This study found that wearing stockings on both legs during flight significantly reduced the risk of VTE, with an OR of 0.1 (95% CI, 0.04–0.25, P<0.00001).¹² Similarly, it was found that graduated compression stockings (GCS) prevented travel-related VTE (P<0.05 in 4 of 6 studies).⁸ In that review, low-molecular-weight heparin (LMWH) showed a trend toward efficacy in reducing VTE risk, while aspirin had no effect. Interestingly, a prospective cohort study analyzing patients with acute VTE after long travel time found that travelers with VTE used LMWH prophylaxis significantly less frequently compared to others in a VTE patient registry (2.4% vs 1.3%, OR=0.2, 95% CI, 0.1–0.3).¹³

Table 2.

Studies assessing efficacy of thromboprophylaxis

Author (year published); study type	Patient population	Study intervention comparator	Endpoint results/Outcome	Study limitations
Clarke et al (2021); systematic review; 11 RCTs11	RCTs of compression stockings on 1 or both legs vs no stockings or another intervention in passengers on flights ≥4h	Intervention: 12 randomized trials (n=2918) were included; 10 (n=2833) compared wearing stockings on both legs vs not wearing them; 1 (n=35) compared wearing a stocking on 1 leg for the outbound flight and on the other leg on the return flight. One compared compression tights (n=50).	Results: 50 participants had a symptomless DVT; 3 wore stockings, 47 did not (OR=0.10; 95% CI, 0.04–0.25; P<0.00001). Wearing stockings had a significant impact in reducing edema (based on 6 trials). No significant adverse effects were reported.	None
Hitos et al (2007); prospective cohort; n=2115	21 healthy volunteers (21 limbs) with no history of thrombosis, leg trauma, swelling, surgery, lymphedema, venous reflux, or outflow obstruction	Intervention: Popliteal vein blood flow measured with subjects sitting motionless, sitting with feet off floor performing airline-recommended activities, foot exercises, foot exercises against moderate resistance, and foot exercises against increased resistance.	Results: Blood volume flow in the popliteal vein was reduced by almost 40% with immobility of seated subjects and by almost twofold when sitting motionless with feet not touching the floor. Foot exercises against increased resistance positively enhanced volume flow (P<0.0001).	Incomplete or inadequately short follow-up.
Kuipers et al (2007); systematic review; 55 studies2	Studies of air travel with VTE	Intervention: RCTs (n=11): assessed the effect of various prophylactic measures on the risk of VTE after air travel.	Results: RCTs: Due to high risk of bias among studies, the results were not discussed in the systematic review.	Quality of studies was not appraised or studies were of low quality. Methods and/or results were inconsistent across studies.
Tsoran et al (2010); prospective cohort study; n=26,17213	Consecutive patients with symptomatic, acute (DVT) or PE, confirmed by objective tests	Intervention: Registry records patients’ baseline characteristics; risk factors for VTE, including 6-h and longer traveling during the past 3 wk and the mode of traveling; clinical characteristics of the VTE event; usage of LMWH prophylaxis.	Results: Travelers used LMWH prophylaxis significantly less frequently than other patients in the registry (2.4% vs 13%; OR=0.2; 95% CI, 0.1–0.3).	Differences in important prognostic factors at baseline.
Philbrick et al (2007); systematic review; 25 studies8	Primary data concerning the risk of travel for VTE or tested preventive measures for travel-related VTE	Intervention: Prevention (9 RCTs)	Results: Prevention: Graduated compression stockings prevented travel-related VTE (P<0.05 in 4 of 6 studies), aspirin did not, and LMWH showed a trend toward efficacy in 1 study.	Quality of the studies was not appraised or studies were of low quality. Methods and/or results were inconsistent across studies.
Belcaro et al (2018); registry study; n=29514	Patients at different levels of DVT risk flying in economy class for more than 8 h, twice in less than 7 d	Intervention: Subjects were subdivided in 3 groups according to their risk level (low, moderate, or high). All risk groups were divided by 3 interventions: The high-risk group also received aspirin. The standard management (control) group included education about DVT and its prevention during travel, a group receiving pycnogenol (150 mg·d−1 equivalent to 3 cps·d−1 was started 3 d before the flights and stopped 3 d after the second flight), and a group wearing stockings.	Results: Low-risk group n=105 (33 pycnogenol, 36 controls, 36 stockings): Edema was reduced more (P<0.05) with pycnogenol and stockings compared to control. Pycnogenol reduced edema significantly more than the stockings (P<0.05). Ankle circumference was smaller with pycnogenol (P<0.05). No thrombosis was detected. Thermal imaging revealed no hot spots, indicating the absence of an inflammatory of thrombosed area. Medium-risk group n=108 (32 pycnogenol, 38 controls, 38 stockings): Edema and ankle circumference were lower in the pycnogenol group (P<0.05). One DVT and 1 minimal SVT was seen in controls. High-risk group n=82 (25 pycnogenol, 25 control, 32 stockings): Edema and ankle circumference were significantly reduced in the pycnogenol group (P<0.05) compared to both controls and stockings. There was no SVT or DVT in the pycnogenol group. One minimal DVT and 1 SVT were observed in controls.	Failure to adequately control confounding.

DVT, deep vein thrombosis; LMWH, low-molecular-weight heparin; OR, odds ratio; PE, pulmonary embolism; RCT, randomized control trial; SVT, superficial vein thrombosis.

The last systematic review only discussed one thromboprophylaxis trial due to high risk of bias among other studies and noted that use elastic compression stockings had a relative risk of 0.04 (0–0.6) for VTE.²

A registry study evaluating the development of edema and vein thrombosis in subjects with different levels of risk for thrombosis using prophylaxis found that a natural supplement of French maritime pine bark significantly decreased edema compared to both stockings and the control for all risk groups (P<0.05).¹⁴ The authors noted no DVTs in the groups taking the supplement or wearing stockings, only in the control groups.

A prospective cohort study analyzing factors affecting popliteal venous blood flow found that blood flow was decreased by almost 40% when patients were seated without mobility and by 48% when they sat motionless without feet touching the floor. They had subjects do a series of exercises of increasing intensity and found that the most rigorous foot exercises against increased resistance increased blood flow significantly (P<0.0001).¹⁵ However, no known trials have specifically studied exercises with thrombosis as an endpoint.

As with the association between length of travel and VTE, the available research is of low quality. Compression stockings have the strongest data to suggest a pro-phylactic benefit. Two studies both found that GCS decrease VTE risk, but as before, the quality of evidence is low due to study inconsistency.^8,12 We found no study to suggest anticoagulation is effective in travelers for preventing VTE. The nonrandomized studies were limited by failure to control confounding factors, inadequate follow-up, and differences in prognostic indicators at baseline.

PUBLISHED GUIDELINES

We analyzed guidelines on VTE prophylaxis in nonsurgical patients from 5 sources. The strength of the guidelines was generally low, with 2 sources writing conditional recommendations^16,17 and the other 2 based on low evidence grades.^18,19

The American Society of Hematology’s 2018 guideline for VTE in nonsurgical patients included conditional recommendations based on very low certainty in the evidence about effects. For long-distance travel (>4 h) in travelers without known risk factors for VTE, they recommended against prophylaxis (including GCS, LMWH, or aspirin), although they acknowledged that GCS may be used in travelers who place a high priority on VTE prevention and noted that GCS reduce edema, which may make travel more comfortable for some. In people at substantially increased risk for VTE (eg, recent surgery, history of VTE, hormone replacement therapy, pregnant or postpartum women, active malignancy, or 2 or more risk factors), they recommended prophylaxis with GCS or LMWH for travel >4 h. If neither GCS nor LMWH is feasible, they recommended using aspirin rather than no treatment.¹⁷

The Saudi Arabia Ministry of Health’s 2017 guidelines recommended frequent ambulation, calf muscle exercise, sitting in the aisle seat, and anticoagulants for high-risk travelers on journeys >8 h. They recommended against using GCS for prophylaxis.¹⁶

The American College of Chest Physicians 2012 guideline recommendations were similar to the Saudi Arabian recommendations, as they suggested frequent ambulation, calf muscle exercise, and sitting in the aisle seat. They differ in that they did suggest GCS (15–30 mm Hg of pressure) for high-risk travelers. The American College of Chest Physicians recommended against GCS in non–high-risk travelers, and they recommended against the use of anticoagulants or aspirin in VTE prevention. All evidence is Grade 2C.¹⁸

The American College of Obstetricians and Gynecologists released a committee opinion in 2018, which recommended preventative measures such as support stockings and periodic movement of the lower extremities, avoidance of restrictive clothing, occasional ambulation, and maintenance of adequate hydration in all pregnant women flying in order to lower the potential risk of edema and DVTs. They acknowledged that there was no strong evidence associating air travel and DVTs during pregnancy.²⁰

Finally, the British Society of Haematology recommended that travelers at increased VTE risk wear below-knee compression hosiery (Grade 2B). If medication is indicated, they recommended use of anticoagulants over antiplatelet agents (Grade 2C). Maintaining mobility was recommended for all travelers on journeys over 3 h due to likely pathogenesis of travel-related VTE (Grade 2B), but use of GCS or anticoagulants for all travelers was not recommended (Grade IC).¹⁹

In summary, there is significant discord among guideline recommendations, with all groups acknowledging that the level of evidence is very low.

Discussion

The best available studies find an association between VTE and travel, but the available data show only a mild to moderate increased association, with high heterogeneity among studies. Odds ratios vary from as low as 1.1¹⁰ to 4,⁶ but generally point to a link between travel and VTE, with 7 out of 10 studies showing a significant association between the two. Germane to our question, a dose-response relationship can be identified, with studies finding increased risk of VTE and severe PE after longer flights compared to shorter ones.^2,7–9 Although the studies used a variety of flight times to assess effects after “longer” flights, increased risk of VTE was noted even when the cut-off was as low as >4 h, indicating that travel does not need to be especially extensive to pose an increased risk. Although some studies attempted to identify other potential risks, there were not many clear associations between other travel factors and VTE.^21,22 For example, despite the common name of “economy class syndrome,” flying business class did not significantly lower the risk, although window seating did increase the risk twofold.²¹ It is difficult to come to a stronger conclusion due to the low quality of evidence and high heterogeneity within and among studies.

Although the data on thromboprophylaxis and VTE are similarly low quality, low-risk prophylactic measures such as GCS were shown to be effective.^8,12,15 The data do not elucidate the role of pharmacologic anticoagulation. LMWH showed a trend toward efficacy in one study,⁸ and travelers with VTE used LMWH less frequently than others in another,¹³ but no study showed a significant change in VTE risk with pharmacoprophylaxis. The available guidelines all differ slightly but largely follow the prophylaxis data. In general, the guidelines recommend against prophylactic measures in patients without known VTE risk factors. This is appropriate as clinical VTE after travel is a rare event in patients.⁸ In patients with risk factors for VTE, the guidelines generally advocate for conservative interventions such as GCS^17–19 and maintaining frequent ambulation with calf exercises.^16,18,19

The key finding of this review is the poor quality of data describing travel-associated VTE and the lack of evidence for prophylaxis. Better observational data to define risk and prospective trials of prophylaxis in high-risk patients will better answer these questions going forward. Until the time such data are available, providers must make decisions based on the limited data we have and appropriate clinical judgment.

Despite this uncertainty, the issue of thrombosis with travel is frequently brought up by both patients and providers. Until there are more robust data, the following can be recommended:

• Air travel is a risk factor for VTE and there is a dose effect starting at 4 h.

• For patients with risk factors—or those concerned about thrombosis—GCS 15 to 30 mm Hg can be recommended.

• Guidelines emphasize the role of hydration and ambulation for all passengers.

Although frequently prescribed, there is only limited data for LMWH prophylaxis—and none yet for the direct oral anticoagulants. Pharmacologic prophylaxis either with LMHW or with direct oral anticoagulants may be considered for very high-risk patients (eg, history of thrombosis, cancer), with acknowledgement of the very limited data available.

Given the vast numbers of people who travel, there is a need for solid clinical data to estimate risk of travel-related thrombosis. Important clinical trials could include examining the VTE risk at increasing flight lengths (eg, 3 vs 4 h; 4 vs 5 h) so that we could better establish a time limit above which risk is increased. This would be helpful clinically as the available data do not offer a unifying definition of what is a “longer,” and thus riskier, flight. As many people travel long distances not only by plane but also by car and train, another possible trial could examine VTE risk with specific modes of transportation. Currently, the data tend to describe risk due to flight alone, to all modes of transportation, or to all modes except flight. It would be helpful to know specifically whether the increased risk we see with air travel also applies to travel by car and train. If that same risk does not exist, it not only changes clinical practice but also implies that there is some quality about air travel in particular, beyond the time spent, that increases thrombotic risk. This too could be an area of study as the pathophysiologic studies on air travel do not offer a clear mechanism of disease. Finally, studies need to be performed to better define the role—if any—of pharmacologic prophylaxis.

Conclusions

The available evidence is of low quality both for defining risk of air travel and thrombosis as well as preventive measures. We conclude air travel is a risk factor for VTE and that there is a dose relationship starting at 4 h. For patients with risk factors, GCS are effective prophylaxis. Further high-quality studies are needed both to better define the risk of and to prevent travel-related thrombosis.