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Is this case of deep vein thrombosis provoked or unprovoked?

December 30, 2021
Elisabeth M. Battinelli, MD, PhD
Associate Physician, Brigham and Women's Hospital, Assistant Professor of Medicine, Harvard Medical School, Boston, Massachusetts

This month Beth Battinelli, MD, PhD, discusses thrombosis development after extended travel.

And don't forget to check out next month's clinical dilemma – send in your responses for a chance to win an ASH Clinical News-themed prize!


A healthy 42-year-old woman not on estrogen flew 2.5 hours to North Carolina – plus time spent sitting in the terminal. She flew home two days later. The next morning she drove 2.5 hours to her sister's home and returned home the following morning. Three days later she was diagnosed with a lower extremity deep vein thrombosis (DVT). Would you consider her DVT provoked or unprovoked? Would three months of anticoagulation be okay, or does she need D-dimers to help decide? If you consider her DVT to be unprovoked, how long should she be anticoagulated?


Beth M. Battinelli, MD, PhD: Although we usually think of air travel as associated with thrombosis, this complication can occur with extended travel by other modes of transportation, including car, bus, or train. Each year, more than 300 million people travel long distances by air (defined as greater than 4 hours in the air). One serious adverse event that occurs for some long-distance travelers is the development of a venous thromboembolic event (VTE). Based on observational studies, an estimated one in 500 individuals (≥50 years old) who fly long distances will develop a VTE. A recent study suggested that the risk is cumulative for each two hours of prolonged air travel culminating in a risk of 18 percent. Other risk factors can clearly affect overall risk, including previous VTE, thrombophilia, obesity, hormone-based therapies, recent surgery, or active malignancy. Although evidence suggests that the risk of venous thrombosis increases after air travel, questions remain about the underlying mechanism, as well as whether the mode of transportation is significant.

It is also clear that the risk does not end with the cessation of travel. Studies report that increased risk of VTE persists for the first two weeks after initiation of travel. MacCallum and colleagues carried out a case-control study, which included 550 VTE cases identified from practice records. Compared with patients who had no recent history of travel, the risk to those who had a cumulative flying time of greater than 12 hours in the previous four weeks was associated with a three-fold increased risk of VTE. In addition, those who had a single leg of travel greater than four hours had a two-fold increased risk.1 This would suggest that cumulative travel over a period of days to weeks can increase an individual's overall thrombotic risk.

In the RIETE registry (Registro Infomatizado de Enfermedad ThromboEmbolica), the authors assessed the thromboembolism prevalence in different groups of travelers, and revealed that when it comes to car travel, the drivers had a higher rate of VTE than passengers.2 In the MEGA (Multiple Environmental and Genetic Assessment) study, which is a large, ongoing case-control study on risk factors for venous thrombosis in an unselected population, all modes of travel were associated with a two-fold increased risk of venous thrombosis.3 The risk of flying was the same as the risk of traveling by car, bus, or train. The overall risk was highest in the first week after traveling. Risk of thrombosis in individuals traveling by car, bus, or train was influenced by other risk factors such as thrombophilia, obesity, or the use of hormone therapies.

In the case in question, the patient had cumulative travel of 10 hours over the course of a few days. Based on the studies previously mentioned, this would suggest that the car travel was a provoking factor increasing her risk of VTE. I would follow current guidelines for three months of anticoagulation. The patient may have other risk factors such as obesity, recent surgical intervention, or malignancy that could increase her risk of VTE going forward and dictate a longer course of antithrombotic therapy.


  1. MacCallum PK, Ashby D, Hennessy EM, et al. Cumulative flying time and risk of venous thromboembolism. Br J Haematol. 2011;155:613-9.
  2. Tsoran I, Saharov G, Brenner B, et al. Prolonged travel and venous thromboembolism findings from the RIETE registry. Thromb Res. 2010;126:287-91.
  3. Cannegieter SC, Doggen CJ, van Houwelingen HC, et al. Travel-related venous thrombosis: results from a large population-based case control study (MEGA study). PLoS Med. 2006;3:e307.

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Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.


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