Stephan Moll, MD writes… Can the person with a newly diagnosed DVT or PE safely fly, or should he/she wait for a few weeks before flying? It appears o.k. to fly early. There is no evidence that flying early after the diagnosis of DVT or PE leads to an increased risk of recurrent clots or breaking off of clots from a DVT to form a PE, as long as the patient is on adequate blood thinner treatment.
Airline travel and Blood Clots
a) The person NOT on blood thinners
Airline travel is an established (mild) risk factor for DVT and PE in the patient who is NOT on blood thinners [ref 1,2]; the longer the travel, the higher the risk for clots . Typically, multiple risk factors come together –overweight, hormone therapy (e.g. contraceptives), recent surgery, trauma, or hospital stay, cancer, genetic or acquired clotting disorders, and the immobility from the travel itself. It has also been suggested that the decreased air pressure in the airplane cabin might lead to activation of the clotting system and an increased risk for DVT or PE, particularly in persons with one or more of the above underlying risk factors [ref 4]. However, neither have published data on this issue been consistent, nor is it clear whether such changes are really relevant for the traveller.
b) The patient with VTE who is on blood thinners
- Is there an increased risk for recurrent DVT or PE or clot breaking off from a DVT? It is not known whether the risk for recurrent clot or the risk for a DVT to break off to cause a PE is increased with airline travel in the patient who is on blood thinners. Any potential activation of the clotting system by the decreased cabin pressure while flying is very likely counteracted by the fact that the patient is on a blood thinner. Thus, an increased failure rate of blood thinners (i.e. progression of DVT or PE; increased risk of DVT leading to PE) is not likely.
- Is there worsened leg swelling in the patient with DVT? The patient with acute DVT and leg swelling may experience somewhat more swelling during or after the flight – not because of worsening DVT, but because of increased fluid retention in the legs from the decreased air pressure in the cabin. Many healthy people experience that, too. Also, the distances to walk and the prolonged standing in the airport may lead to increased leg swelling. However, this is not expected to lead to worsening DVT or a new DVT.
- Is there worsened shortness of breath in the patient with PE? The patient who has had a large PE or has other underlying lung disease (COPD, etc.) may have some worsening of shortness of breath during flying – not because of new PE, but because the airplane cabin contains slightly less oxygen than the air at sea level.
In general, I discuss with the patient who has a new DVT or PE that…
- it appears to be o.k. to fly immediately after the DVT or PE diagnosis, as long as the person is on full-dose blood thinners.
- airline travel is not expected to lead to an increased risk of new DVT or PE or breaking off of clots from a DVT.
- leg swelling in the person with DVT may temporarily worsen during and in the few days after airline travel due to the lower air pressure in the airline cabin.
- shortness of breath in the person with a fairly large PE may be somewhat worse during airline travel due to the mildly decreased oxygen content in the airline cabin.
- it may be worthwhile to delay a flight for at least a few days, to be sure that the patient is stable, no unexpected issues occur, and/or the patient has had time to adapt to this new, potentially life-modifying diagnosis and treatment.
As always, individualized medical decisions need to be made.
- Chandra D et al. Meta-analysis: Travel and risk for venous thromboembolism. Ann Intern Med 2009;151:180-190.
- Cannegieter SC. Travel-related thrombosis. Best Pract Res Clin Haematol. 2012 Sep;25(3):345-50.
- Schreijer AJ et al. Activation of coagulation system during air travel: a crossover study. Lancet 2006 Mar 11;367(9513):832-8.
- Schreijer AJ et al. Explanations for coagulation activation after air travel. J Thromb Haemost 2010 May;8(5):971-8.
I appreciate the discussions with Dr. Richard Moon, Medical Director, Center for Hyperbaric Medicine & Environmental Physiology, Duke University Medical Center, Dr. Claude Piantadosi, Interim Chief, Division of Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center, and Dr. Philip Blatt, Adjunct Professor of Internal Medicine and Hematology, Duke University Medical Center, Durham, NC.
Last updated: July 12th, 2017
Stephan Moll, MD and Damon Houghton, MD write … Antiphospholipid syndrome (APS) is an acquired clotting disorder. Patients with APS may have DVT or PE that requires treatment with blood thinners. Warfarin (Coumadin®, Jantoven®), and sometimes the injectable heparin drugs (enoxaparin = Lovenox®; dalteparin = Fragmin®; tinzaparin = Innohep®; etc.), have traditionally been used in patients with APS. A question that comes up is whether one of the new oral blood thinners (apixaban = Eliquis®; dabigatran = Pradaxa®; edoxaban = Savaysa®; rivaroxaban = Xarelto®) can be used instead of warfarin or a heparin drug. These drugs are collectively referred to as direct oral anticoagulants (DOACs).
It is not known at this point whether DOACs are equally, more or less effective as/than warfarin in patients with APS. Data from clinical trials directly comparing DOACs with warfarin are not yet available. Given the absence of data, no formal recommendations or guidelines exist on this topic. It is an individualized decision between a physician and patient with APS whether to use warfarin or a DOAC for the treatment of DVT or PE.
Multiple cases of patients with APS treated with a DOAC have been published. All of these (i.e. a total of 122 patients) have recently been summarized [ref 1]: Sixteen percent (i.e. one of every 6 patients) had a recurrent clot on a DOAC. As this is a high rate of DOAC failure, the authors caution about the use of DOACs in APS. However, two things need to be considered: (a) it is also known that warfarin has a high failure rate [references 2,3]; and (b) due to the nature of case report publications (potential bias; absence of control group), no strong or meaningful conclusion is really possible as to how DOACs compare to warfarin in the treatment of DVT and PE in patients with APS
Several studies on APS and the use of DOACs are ongoing. Details of the following studies can be found at clinicaltrials.gov:
- NCT02157272: A Prospective, Randomized Clinical Trial Comparing Rivaroxaban with Warfarin in High Risk Patients With Antiphospholipid Syndrome (TRAPS)
- NCT02295475: Apixaban for the Secondary Prevention of Thromboembolism Among Patients With the AntiphosPholipid Syndrome (ASTRO-APS)
- NCT02116036: Rivaroxaban for Antiphospholipid Antibody Syndrome (RAPS)
This is what we discuss with the patient with APS who needs to be on a blood thinner:
- I highlight that no solid data exist regarding the use of DOACs in APS, and that it is not known whether the DOACs are as effective as warfarin, less effective or more effective.
- I discuss the fact that some patients with APS develop new clots in spite of being on warfarin and that recurrent clots may also occur on a DOAC.
If we decide to use a DOAC, then our preference is typically to use a twice daily dosed blood thinner (Eliquis® or Pradaxa®) rather than a once daily dosed drug (Xarelto® or Savaysa®). The thought behind this is that a twice daily dosed drug leads to more steady drug levels throughout the day and that this may lead to a more effective blood thinning effect. However, this is a theory unproven, and whether this truly leads to a lower risk of recurrent clots than being on a once daily drug is not known. A recent publication of a case report with discussion of drug metabolism also favors a twice daily rather than a once daily dosed drug in patients with APS [ref 4]. Ultimately, the most effective medication is likely the one that is taken as prescribed; therefore, a patient’s preference regarding the feasibility and practicality of a once daily versus twice daily medication is also an important consideration.
- Dufrost V et al. Direct oral anticoagulants use in antiphospholipid syndrome: Are these drugs an effective and safe alternative to warfarin? A systematic review of the literature. Curr Rheumatol Rep 2016;18:74.
- Crowther M et al. A Comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003;349:1133-8.
- Finazzi G et al. A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS) J Thromb Haemost 2005;3: 848–853.
- Schofield JR et al. Dosing considerations in the use of the direct oral anticoagulants in the antiphospholipid syndrome. J Clin Pharm Ther. 2017 Jun 27. doi: 10.1111/jcpt.12582. [Epub ahead of print].
Disclosure: Dr. Moll has consulted for Janssen Pharmaceuticals and Boehringer-Ingelheim. Dr. Houghton has no disclosures.
Last updated: July 5th, 2017
Stephan Moll, MD writes… Today, June 23, 2017, the FDA approved a 5th new oral blood thinner for clinical use, Bevyxxa® (= Betrixaban), taken once daily. It is FDA approved to prevent blood clots (DVT and PE) for patients who are significantly immobile and, therefore, at increased risk for blood clots during and after hospitalization for an acute medical illness. Full prescribing information: here. FDA details: here.
In the study that led to FDA approval (APEX study; reference 1), Bevyxxa® was given for 5-6 weeks during and after hospitalization to patients with acute medical illnesses (heart failure, respiratory failure, infectious disease, rheumatic disease, or stroke) who had reduced mobility. Fewer blood clots happened in the patients treated with the drug, without an increase in major bleeding.
Consequences for my Practice
Bevyxxa® has not been studied in patients who have a DVT or PE and should not be used in such patients. However, it can be considered for 5-6 weeks for significantly immobile patients who are at high risk for a blood clot during and after a hospital admission for a severe acute medical illness.
- Cohen AT et al. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. APEX Investigators. N Engl J Med. 2016 Aug 11;375(6):534-44.
Disclosure: Dr. Moll has consulted for Portola, Janssen, and Boehringer-Ingelheim.
Last updated: June 25th, 2017
Can Athletes With DVT or PE Return To Play? Fact-Based Rather Than Emotional Reasoning
Stephan Moll, MD1, Joshua Berkowitz, MD2, Philip Blatt, MD, FACP3
Every so often news hit the media that a prominent athlete has had a blood clot: NBA athlete Chris Bosh and NHL’s Steven Stamkos most recently, NBA’s Mirza Teletović and NHL’s Cody McCormick in 2015, tennis player Serena Williams in 2011 Read the rest of this entry »
Stephan Moll, MD writes… The FDA did NOT approve Andexanet (brand names: AndexXa™ in the US, IndexXa™ in Europe) in a decision on August 18th, 2016. Andexanet is the drug in clinical trials as an antidote to reverse the blood thinning effect of Eliquis®, Savaysa®, Xarelto® and Lovenox® (= enoxaparin). The FDA is said to have requested more information from the company (Portola) making Andexanet, specifically (a) additional information related to manufacturing of the drug, and (b) more data to support inclusion of Savaysa and Lovenox (enoxaparin) in the label. The FDA also wants to finalize its review of the company’s proposals for post-marketing data collection on the performance of the drug.
It needs to be seen when the company (Portola) submits the requested additional information and when a new decision from the FDA is then to be expected. My guess is that this will be sometime in 2017.
- Portola announcement from Aug 18, 2016: http://bit.ly/2c1wKaK
- Connolly SJ et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. NEJM 2016;Aug 30 [e-pub]
Disclosure: I have consulted for Portola, Janssen, and Boehringer-Ingelheim.
Last updated: Aug 31st, 2016
Stephan Moll, MD writes… Interesting observations published in the last 2 weeks: Heavy menstrual bleeding appears to occur more commonly with Xarelto® than with warfarin [ref 1] and may be also more common with Xarelto® than with Eliquis® [ref 2]. Read the rest of this entry »
Stephan Moll, MD writes… Interesting and relevant publication this week [reference 1]. It is well known that estrogen–containing birth control methods (pills, vaginal rings, patches, injectables) increase the risk for DVT and PE. As women on blood thinners may have heavy menstrual bleeds, hormonal therapy may be considered to decrease the bleeding. Also, women on blood thinners may want to choose a method for contraception other than a progestin IUD (Mirena® IUD, Skyla® IUD).
The newly published study Read the rest of this entry »
Stephan Moll, MD writes… An article for patients discussing (a) IVC filters (inferior vena cava filters; also often referred to as “Greenfield filters”), (b) narrowing of the main left pelvic vein (referred to as May-Thurner syndrome) and (c) stents in veins in the pelvis has just been published (http://circ.ahajournals.org/content/133/6/e383.full.pdf). Color images are included helping explain what these conditions are.
Reference: Carroll S, Moll S. Circulation. 2016;133:e383-e387
Last updated: Feb 18th, 2016
Stephan Moll, MD writes… A research study is being conducted at the University of Minnesota by Dr. Pamela Lutsey. The goal of the study is to learn more about patients’ concerns and preferences regarding blood thinner use for the treatment of DVT and PE. The results will help investigators better create future clinical studies to improve treatment of DVT and PE. This is NOT a pharmaceutical industry or marketing survey. If you are a patient who has had a DVT or PE it would be great if you were willing to take the short survey. It will take about 10 minutes to complete. Thank you very much. The following link will direct you to the secure survey site: z.umn.edu/vtesurvey.
Last updated: Jan 28,2016
Stephan Moll, MD writes… A new consensus guidance for health care professionals on management of DVT and PE – link here – was published today, Jan 18th, 2016, in the Journal of Thrombosis and Thrombolysis. The publication contains 13 chapters on various aspects of DVT and PE (acute treatment, decisions on length of blood thinner treatment, thrombophilia work-up, management at times of surgery, etc.). It incorporates both evidence-based data and consensus opinion of the 52 international experts who wrote these chapters. It is aimed at any type of health care professional who is involved in the management of DVT and PE – emergency room physicians, hospitalists, internists, cardiologists, hematologists, pharmacists and others.
Last updated: Jan 18th, 2016