Stephan Moll, MD writes… Can the patient with acute DVT or PE safely fly, or should he/she wait for a few weeks before embarking on airline travel? It appears safe to fly early: There is no evidence that flying early after the diagnosis of VTE leads to an increased risk of recurrent VTE or embolization from a DVT, as long as the patient is on adequate anticoagulation.
Airline travel and Thrombosis
a) The person NOT on anticoagulation
Airline travel is an established (mild) risk factor for DVT and PE in the patient who is NOT on anticoagulation [1,2]; the longer the travel, the higher the risk for thrombosis . 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 hypobaric atmosphere in the airplane cabin might lead to coagulation activation and an increased risk for VTE, particularly in persons with one or more of the above underlying risk factors for VTE [ref 4], but neither have data on this issue been consistent, nor is it clear whether such changes are clinically relevant.
b) The patient with VTE who is on anticoagulation
- Is there an increased risk for recurrent DVT or PE or embolization from a DVT? It is not known whether the risk for recurrent VTE or the risk for a DVT to embolize is increased with airline travel in the patient who is on anticoagulation for a previous VTE. Any potential coagulation activation by the hypobaric cabin environment is likely counteracted by the fact that the patient is on anticoagulation. Thus, an increased anticoagulation failure rate (i.e. progression of DVT or PE; increased risk of DVT leading to PE) is not likely. And while the reduction in ambient cabin pressure per se leads to a small reduction in a patient’s partial pressure of oxygen (PO2) and this may lead to mild vasodilatation and an increase in cardiac output, this is not likely to increase the risk of embolization from a DVT.
- Do patients with DVT develop increased leg swelling while flying? The patient with acute DVT (or postthrombotic syndrome) and leg swelling may experience somewhat more leg swelling during or after the flight – because of leg edema from an increase in capillary permeability in the hypobaric cabin environment, not because of DVT progression. Also, the distances to walk and the prolonged standing in the airport may lead to worsened leg edema. However, this is not expected to lead to progressive or recurrent DVT.
- Do patients with PE develop increased shortness of breath while flying? The patient who has a large PE or has other underlying hypoxic lung disease (COPD, etc.) may have some worsening of shortness of breath during flying – not because of new PE, but because the cabin’s environment is mildly hypoxic.
Rules by the International Air Transportation Association (IATA) limit the decrease in cabin pressure in commercial aircraft to an equivalent altitude of 8,000 ft (564 mmHg, 0.74 ATA), although most planes maintain their pressures at an equivalent altitude of around 5,000 ft (632 mmHg, 0.83 ATA). Thus, the predicted decrease in a patient’s arterial PO2 is small, and would be clinically significant only for people with pre-existing hypoxemia.
In general, I discuss with the patient who has an acute DVT or PE and wants to fly soon that…
- he/she can fly, even immediately after the VTE diagnosis, as long as he/she is on full-dose anticoagulation.
- that airline travel is not expected to lead to an increased risk of recurrent VTE or embolization from a DVT.
- leg swelling in the patient with DVT may temporarily worsen during and in the few days after airline travel due to the hypobaric pressure in the airline cabin.
- shortness of breath in the patient with a 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.
- 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 … In patients with antiphospholipid syndrome (APS) who require anticoagulation for the treatment of DVT or PE, warfarin or a low molecular weight heparin have traditionally been used. A question that comes up is whether one of the new oral anticoagulants (DOACs) can be effectively and safely used instead.
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.
Several case reports and case series of patients with APS treated with a DOAC have been published. All data (from a total of 122 patients) have recently been summarized : Sixteen percent of patients had a recurrent clot on a DOAC. Given this relatively high rate of DOAC failure, the authors caution about the use of DOACs in APS. However, it is also known that warfarin has a high failure rate [references 2,3]. In addition, due to the nature of case report publications (potential bias; absence of control group), no strong or meaningful conclusion is possible as to how DOACs compare to warfarin or LMWH in the treatment of DVT and PE in patients with APS.
Several studies on APS and the use of DOACs are ongoing, with details available 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)
We discuss with patient with APS who needs to be on an anticoagulant:
- … 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.
- … 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 a twice daily dosed anticoagulant (Eliquis® or Pradaxa®) rather than a once daily dosed drug (Xarelto® or Savaysa®), as the twice daily dosed drug leads to more steady drug levels throughout the day. The hypothesis is that this may lead to a more effective anticoagulant effect. However, this theory is unproven and whether this truly leads to a lower risk of anticoagulant failure in patients with APS is not known. A recent publication (case report plus discussion on drug pharmacokinetics/-dynamics) also suggests a twice daily rather than a once daily dosed drug in patients with APS if a DOAC is used [ref 4]. However, feasibility/practicality of once daily versus twice daily medication and, thus, patient preference, is also important to consider.
- 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… On June 23, 2017, the FDA approved a 5th new oral anticoagulant for clinical use, Bevyxxa® (= Betrixaban). It is approved to prevent DVT and PE in patients who are significantly immobile during and after hospitalization for an acute medical illness. Full prescribing information: here. FDA details: here.
In the APEX study that led to FDA approval (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 and were at high risk for VTE. It was compared to 10 +/- 4 days of Enoxaparin at prophylactic dose. Fewer VTE (composite of asymptomatic proximal DVT and symptomatic VTE) occurred in the patients treated with Bevyxxa®, without a higher rate of 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. As a hematologist, I am not much involved in the medical care of these patients. The health care professionals who need to judge whether their elderly, sick patients who are discharged from the hospital should be on this drug are probably mostly hospitalists, congestive heart failure services, and those MDs who take care of these medically sick patients in the specific health care system the MD practices in. Similarly, it is those MDs (with input from pharmacists and discharge planners) who should be involved in institutional algorithm/guideline development as to which patients are to be prescribed this treatment.
- 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: July 6th, 2017
Stephan Moll, MD writes: Athletes with DVT or PE and on anticoagulation face significant challenges returning to full athletic activities. A recent publication of the American College of Cardiology discusses individualized management regimens that may return athletes to return to their sport – http://www.bit.ly/2erRLc0.
Last updated: Oct 30th, 2016
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 antidote in clinical development to reverse the anticoagulant effect of Eliquis® (rivaroxaban), Savaysa® (edoxaban), Xarelto® (rivaroxaban) 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® 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 to the FDA 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 and noteworthy 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].
Stephan Moll, MD writes… Interesting and clinically relevant publication this week [ref 1]. It is well known that estrogens and certain progestin preparations increase the risk for venous thromboembolism (VTE). A woman on an anticoagulant may have heavy menstrual bleeds and hormonal therapy – such as estrogen-progestin contraceptives – may be considered to decrease the bleeding.
The newly published study Read the rest of this entry »
Stephan Moll, MD writes… Our medical center (University of North Carolina Hospitals, Chapel Hill) has put together a comprehensive “Emergent Anticoagulation Reversal Guideline” for our local use, updated since its last edition in 2014 with information about Pradaxa® reversal (with Praxbind®). It is a practical, clinical how-to document (2016 PDF here ). Colleagues and hospitals are welcome to take the document, modify it, and apply it to their institution – there are no copyright concerns.
Disclosures: I have been a consultant on one occasion for Boehringer-Ingelheim.
Last updated: May 11th, 2016
Stephan Moll, MD writes… An article for patients discussing (a) IVC filters, (b) narrowing of the main left pelvic vein (May-Thurner syndrome) and (c) pelvic venous stents has just been published (http://circ.ahajournals.org/content/133/6/e383.full.pdf). Color images of anatomy, filters and stents are included as visual aids. The article may be helpful as handout material for patients in clinic.
Reference: Carroll S, Moll S. Circulation. 2016;133:e383-e387
Last updated: Feb 18th, 2016
Stephan Moll, MD writes… A new consensus guidance on management of venous thromboembolism (VTE) – link here – was published today, Jan 18th, 2016, in the Journal of Thrombosis and Thrombolysis. The publication contains 13 chapters on various aspects of VTE Read the rest of this entry »