Each month in “ You Make the Call ,” we ’ ll pick a challenging clinical question submitted through ASH ’ s Consult a Colleague program and post the expert ’ s response , but we also want to know what you would do . Send in your responses to next month ’ s clinical dilemma and see how your answer matches up to the experts ’ in the next print issue .

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

Clinical Dilemma :

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 ?

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

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 longdistance 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 The overall risk was highest in the first week after traveling . evidence suggests that the risk of venous thrombosis Risk of thrombosis in individuals traveling by car , bus , or increases after air travel , questions remain about the train was influenced by other risk factors such as thrombophilia , obesity , or the use of hormone therapies . underlying mechanism , as well as whether the mode of transportation is significant .

In the case in question , the patient had cumulative It is also clear that the risk does not end with the travel of 10 hours over the course of a few days . Based cessation of travel . Studies report that increased risk of on the studies previously mentioned , this would suggest VTE persists for the first two weeks after initiation of that the car travel was a provoking factor increasing her travel . MacCallum and colleagues carried out a casecontrol study , which included 550 VTE cases identified months of anticoagulation . The patient may have other

risk of VTE . I would follow current guidelines for three

from practice records . Compared with patients who had risk factors such as obesity , recent surgical intervention , no recent history of travel , the risk to those who had a or malignancy that could increase her risk of VTE going cumulative flying time of greater than 12 hours in the forward and dictate a longer course of antithrombotic previous four weeks was associated with a three-fold therapy . increased risk of VTE . In addition , those who had a

REFERENCES single leg of travel greater than four hours had a two-fold increased risk . 1 This would suggest that cumulative travel 1 . MacCallum PK , Ashby D , Hennessy EM , et al . Cumulative flying time and risk of venous thromboembolism . Br J Haematol . 2011 ; 155:613-9 . over a period of days to weeks can increase an individual ’ s

2 . Tsoran I , Saharov G , Brenner B , et al . Prolonged travel and venous thromboembolism findings overall thrombotic risk . from the RIETE registry . Thromb Res . 2010 ; 126:287-91 . In the RIETE registry ( Registro Infomatizado de

3 . Cannegieter SC , Doggen CJ , van Houwelingen HC , et al . Travel-related venous thrombosis : results Enfermedad ThromboEmbolica ), the authors assessed from a large population-based case control study ( MEGA study ). PLoS Med . 2006 ; 3 : e307 . 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 Visit ashclinicalnews . org / you-make-the-call to view increased risk of venous thrombosis . 3 The risk of flying next month ’ s clinical dilemma , and send in your responses to ashclinicalnews @ hematology . org was the same as the risk of traveling by car , bus , or train .

●

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• Anemias

• Hematopoietic cell transplantation

• Hemoglobinopathies

• Hemostasis / thrombosis

• Lymphomas

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• Leukemias

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Assigned volunteers (“ colleagues ”) will respond to inquiries within two business days ( either by email or phone ).

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52 ASH Clinical News September 2017

You Make the Call

Expert Opinion

Next Month ’ s Clinical Dilemma :

Consult a Colleague Through ASH

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 .

September 2017 You Make the Call

Want to Learn More ? ASH is collaborating with the GRADE center at McMaster University to develop clinical practice guidelines on the diagnosis and treatment of VTE . For more details , visit hematology . org / guidelines .

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 postsurgical 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 .

10 ASH Clinical News November 2017