A Thought-Provoking Question

In our September issue, Elisabeth M. Battinelli, MD, PhD, responded to a colleague seeking advice on managing a patient who developed deep-vein thrombosis (DVT) after extended periods of travel. Based on the details of the case, Dr. Battinelli concluded that the DVT was provoked and recommended three months of anticoagulation. As always, we asked readers for their opinions, and we received dozens of responses offering different perspectives on the clinical dilemma. David A. Garcia, MD, professor of medicine at the University of Washington School of Medicine in Seattle, Washington, shared his interpretation of the dilemma – highlighting the lack of evidence to help guide these decisions.


To the editor:

In the September 2017 “You Make the Call,” Dr. Battinelli responded to a question regarding a DVT that developed after extended travel. I respectfully disagree with Dr. Battinelli’s conclusion, perhaps because I have a different interpretation of the available evidence.

After describing a scenario in which a healthy, 42-year-old woman (not taking estrogen) experienced a DVT less than one week after a 2.5-hour flight and a 2.5-hour automobile trip, Dr. Battinelli concluded that this was a “provoked” event and recommended that anticoagulation be discontinued after three months. The implication of this recommendation is that the treating physician is confident that the risk of extended anticoagulation would be greater than the benefit.

While there is high-quality evidence that recurrent venous thromboembolism (VTE) will be very infrequent in patients whose anticoagulation is discontinued three to six months after a post-surgical thrombosis,1 I am not aware of any comparable data that establish a similarly low recurrence risk in patients who stop anticoagulation after travel-associated thrombosis.

I acknowledge that long-distance travel is associated with VTE risk, but the association is much weaker than, for example, the link between surgery and VTE. Indeed, the case-control study cited in Dr. Battinelli’s response indicates that recent high-risk surgery has an odds ratio (OR) for VTE of 140, whereas the corresponding OR for recent travel longer than four hours is 2.2.2 The very small effect of travel on VTE risk is perhaps best illustrated by a systematic review that indicates the risk of a symptomatic VTE event is one per 4,600 flights of more than four hours duration.3

Given the multicausal nature of VTE and the small absolute effect of air travel on thrombosis risk, I am reluctant to conclude that any travel-associated VTE event was “provoked.” Instead, I typically presume that, although the travel likely contributed to the development of thrombosis, most patients who experience a DVT or pulmonary embolism following an airplane flight or a car ride remain at risk for recurrence, if or when anticoagulation is discontinued.

Pending evidence to the contrary, I approach patients with travel-associated VTE as if they had an “unprovoked” event because the available evidence does not establish that the future risk of VTE is low in this population, and extended anticoagulation therapy is quite safe.

Sincerely,
David A. Garcia, MD
University of Washington
Seattle, WA

References

  1. Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study. Lancet. 2003;362:523-6.
  2. MacCallum PK, Ashby D, Hennessy EM, et al. Cumulative flying time and risk of venous thromboembolism. Br J Haematol. 2011;155:613-9.
  3. Kuipers S, Schreijer AJ, Cannegieter SC, et al. Travel and venous thrombosis: a systematic review. JAMA Intern Med. 2007;262:615-34.

Dr. Battinelli’s response:

Although it is true that, as Dr. Garcia pointed out, there is a lack of high-quality, robust clinical trial data on travel-associated VTE, consensus guidelines suggest that travel poses a reversible risk for the development of VTE.

The more nuanced question asked in this “You Make the Call” dilemma was whether the risk was cumulative with multiple shorter intervals of travel. Based on these expert guidelines and studies assessing the cumulative risk of travel, I addressed concerns regarding cumulative exposure to this provoking risk factor.

Guidelines published in Antithrombotic Therapy and Prevention of Thrombosis, 9th edition, establish that provoking reasons for VTE include nonsurgical transient risk factors such as estrogen therapy, pregnancy, injury to an extremity, or travel, and recommend anticoagulation for three months.1 Multiple reviews have characterized the risk factors for thrombosis, and long-distance travel continues to be considered a provoking risk factor.2,3 In a 2010 review, Watson and Baglin nicely summarized the data and established guidelines on travel-related VTE, indicating that, although the risk is small, there is evidence that long-distance travel does represent a risk factor for development of VTE.4 Based on their literature review, they concluded that this applies to all forms of travel and increases based on travel duration.

While new data with direct oral anticoagulants suggest that anticoagulation is safe in this population, again, robust data are lacking on continued, indefinite anticoagulation in this patient population. To date, the longest duration of extended anticoagulation in high-quality clinical trials is just six to 12 months.5,6 Given that the cumulative travel in this patient is felt to be the provoking factor for VTE, in accordance with expert consensus regarding duration of anticoagulation post travel associated VTE, the recommendation to stop anticoagulation at three months is supported.1

Elisabeth M. Battinelli, MD, PhD
Harvard Medical School
Brigham and Women’s Hospital
Boston, MA

References

Kearon C, Aki EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149:315-52.

Crous-Bou M, Harrington LB, Kabrhel C. Environmental and genetic risk factors associated with venous thromboembolism. Semin Thromb Hemost. 2016;42:808-20.

White RH. Identifying risk factors for venous thromboembolism. Circulation. 2012;125:2051-3.

Watson HG, Baglin TP. Guidelines on travel-related venous thrombosis. Br J Haematol. 2010;152:31-4.

Weitz JI, Lensing AWA, Prins MH, et al. Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med. 2017;376:1211-22.

Agnelli G, Butler HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368:700-8.

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