Posts Tagged ‘PE’
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 writes… A plain language summary for patients and interested public about homocysteine and the MTHFR mutations and their relevance in respect to blood clots was published today in the journal Circulation (link here).
Reference: Moll S, Varga EA. Homocysteine and MTHFR Mutations. Circulation. 2015;132:e6-e.
Stephan Moll, MD writes (Dec 17, 2014)… The American Society of Hematology (ASH) published last week two things that physicians dealing with DVT, PE and blood thinners should avoid [ref 1]. Read the rest of this entry »
Stephan Moll, MD writes… For patients stopping blood thinning therapy (anticoagulation) whose deep vein thrombosis (DVT) or pulmonary embolism (PE) was considered unprovoked (i.e. out of the blue and with no obvious triggering, transient cause, such as surgery, hormone use, immobility), aspirin is beneficial in some patients in preventing further clots. A new publication in the journal Circulation re-confirms findings from two previous studies, showing that aspirin reduces the risk of recurrent DVT/PE by more than a third without significantly increasing the risk of bleeding [ref 1,2,3]. Read the rest of this entry »
Stephan Moll, MD writes… Apixaban (Eliquis®) was approved by the FDA this week (Aug 21, 2014) for the treatment of DVT and PE. The approval covers (a) acute DVT/PE management and (b) the longer-term prevention of recurrent DVT/PE. Read the rest of this entry »
Stephan Moll, MD writes… Women are at increased risk for blood clots (DVT, PE, stroke and heart attacks) during pregnancy and in the weeks after delivery. If the risk is high enough, then preventive blood thinners (anticoagulants) are recommended, such as in a woman with a history of a previous blood clot. Guidelines exist as to which woman should be considered for blood thinners (ACOG 2012 guideline; ref 1).
The period after delivery is a particularly high-risk period for forming blood clots. It has typically been defined as being the 6 weeks after giving birth. Therefore, if blood thinners are chosen after delivery, they are classically given for 6 weeks. A study recently published in the New England Journal of Medicine (ref 2) examined whether the risk for blood clots is increased only for 6 weeks postpartum or whether the risk persists beyond the first 6 weeks. Read the rest of this entry »
Stephan Moll, MD writes…
On Oct 8th, 2013 the FDA approved a new drug to treat severe pulmonary hypertension. The drug is called Adempas® (riociguat). Read the rest of this entry »
Stephan Moll, MD writes… This week (Sept 1st 2013) the New England Journal of Medicine published the phase 3 clinical trial of the new oral blood thinner edoxaban compared with warfarin in the treatment of DVT and PE [ref 1]. It showed that edoxaban was as effective as warfarin and led to less clinically relevant bleeding.
- Edoxaban is one of the new oral blood thinners (anti-Xa anticoagulant) that does not require routine m0nitoring for its blood thinning effect and does not interact with vitamin K in the diet like warfarin.
- At this point it is not FDA approved for any indication.
- It is dosed once daily.
- It reaches its peak blood thinning effect within 1 to 2 hours of oral intake.
- Its half-life is 9-11 hours, which means that it is mostly out of the system in 48 hours after stopping it.
- 35 % of the drug is cleared by the kidney, which means that it needs to be dose reduced or avoided in patients with significant impairment of kidney disease.
- This is a randomized, double-blind study.
- All patients received initial therapy with open-label enoxaparin into the skin (subcutaneous) or intravenous heparin for at least 5 days, before edoxaban or warfarin were started.
- Edoxaban was dosed 60 mg once daily. The dose was reduced to 30 mg once daily in patients with impaired kidney function or a body weight less than 60 kg (132 pounds).
- Length of treatment with blood thinners was 3 to 12 months.
- A total of 8292 patients were enrolled (4143 into the edoxaban treatment arm, 4149 into the warfarin arm).
- Recurrent DVT or PE occured in 3.2 % of patients in the edoxaban group and 3.5 % in the warfarin group. Conclusion: edoxaban is not worse than warfarin.
- “Clinically relevant bleeding” occured in 8.5 % of patients in the edoxaban group and 10.3 % in the warfarin group. Conclusion: edoxaban is better than warfarin from a bleeding point of view.
- “Major bleeding” was the same in both groups, 1.4 % in the edoxaban group, 1.6 % in the warfarin group. Conclusion: edoxaban is not worse than warfarin in respect to major bleeding.
The study concludes that edoxaban (a) is as effective as high quality standard therapy with warfarin, and (b) causes less clinically relevant bleeding.
My perspective – Edoxaban compared to the other new oral blood thinners
- This table lists the key differences of the 4 new oral blood thinners in the treatment of VTE.
- Edoxaban is the 4th of the big new oral blood thinners. Its development lags behind the other 3 drugs, which are, at least for the irregular heart beat (atrial fibrillation) indication, already FDA-approved and on the market. For DVT and PE treatment, only rivaroxaban (Xarelto) is FDA-approved; Xarelto is, therefore, the only one of the new oral blood thinners I would use at this time for DVT and PE treatment.
- The main downside of the edoxaban study design is that edoxaban was not started right off the bat once the diagnosis of VTE was made in a patient, but that patients were first treated for at least 5 days with la ow molecular weight heparin (LMWH) blood thinner into the skin or i.v. heparin before edoxaban or warfarin were started. This is similar to the dabigatran study design. The Xarelto and Pradaxa studies, on the other hand, gave the new oral blood thinner immediately after diagnosis, without the need for initial LMWH. Thus, from a clinical-practical point of view, treatment of an acute DT or PE with edoxaban would be more cumbersome (cost of LMWH; teaching of self injections) than treatment with Xarelto or Eliquis.
- Edoxaban is given once daily. This is more convenient for patients than a twice daily regimen, such as with Pradaxa and Eliquis.
- It is good to see data of DVT and PE trials on these various drugs published and the drugs making their way through the FDA approval process and, hopefully, eventually onto the market. It is good to see data on a variety of different patients treated with these drugs, as there are a number of different types of patients which we need to learn more about as to how they fare on the new oral blood thinners: patients who are obese, have kidney impairment, have large PEs, have cancer, etc. The data published in today’s New England Journal of Medicine are a very helpful addition to our knowledge-base.
- HOKUSAI-Investigators. Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 2013;Sept 1.
- Agnelli G et al. Oral Apixaban for the Treatment of acute venous thromboembolism. N Engl J Med, 369:799-808.
- The Einstein Investigators: Oral Rivaroxaban for symptomatic venous thromboembolism. New Engl J Med 2010;363:2499-510.
- The Einstein Investigators: Oral Rivaroxaban for the treatment of symptomatic pulmonary embolism. New Engl J Med 2012;366:1287-97.
- Schulman s et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009 Dec 10;361(24):2342-52.
Disclosure: I have consulted for Janssen, Boehringer-Ingelheim and Daiichi.
Last updated: Sept 2nd, 2013
Stephan Moll, MD writes…
An important study (called AMPLIFY trial) was published today in the New England Journal of Medicine [ref 1]. In a large study of patients with acute DVT or PE, Eliquis (apixaban) was as effective as warfarin and caused less major bleeding. Read the rest of this entry »
Beth Waldron, Clot Connect program director, writes…
If you’ve experienced deep vein thrombosis (DVT) or pulmonary embolism (PE), a recurrence of a blood clot in the future is a concern. Diagnosing a recurrent clot can be a challenge because it is sometimes difficult to tell if symptoms are the result of a new clot or the signs of chronic damage from the initial clot.
- Around 40% of patients with DVT develop long-term pain and swelling, known as post-thrombotic syndrome. Such pain and swelling can fluctuate, and be particularly pronounced after standing for prolonged periods of time or being overly active.
- Around 4% of patients with PE develop long-term shortness of breath, known as pulmonary hypertension.