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Pulmonary Embolism

posted Apr 11, 2011, 9:23 AM by Julie Johnston   [ updated Dec 20, 2011, 4:26 PM by Natalie Cauldwell ]
It had been a seven hour upwind slog from New York to Oklahoma last month. It was reasonable to be tired. But I should have known something was wrong when I gasped for breath after pushing our plane, a Columbia 400, into the hangar. It wasn’t until over a week later, finally on the way to the doctor after days of delay, that I admitted it might be blood clots in my lungs. Sure enough. But at first, in the days following our return flight to New York in the flight levels, I thought the long hours on oxygen or decompression might explain my symptoms. I researched absorption atelectasis and the chokes.

Absorption atelectasis

Alveoli provide extremely efficient oxygen transfer from inhaled gases into solution in the blood in the surrounding capillaries and then into chemical bond with hemoglobin. If those inhalations contain little else but oxygen, and if their pressure is substantially reduced by high altitude, then there is a tendency for the alveoli to collapse. The positive pressure oxygen systems used by military pilots in unpressurized aircraft at high altitudes counteract this tendency. On our return trip at FL230, we were using the type of continuous flow system that is standard in light aircraft, approved for use up to about 25,000 feet. These masks have rebreather bags that help conserve oxygen by mixing some exhaled carbon dioxide and water vapor into inhalations. The presence of those gases in inhalations would also counter collapse of alveoli by tending to hold the overall pressure higher even when the oxygen partial pressure decreased rapidly due to absorption into the blood.

I learned atelectasis is a risk in such flights, but began to look elsewhere after a few days. The condition was not improving, and I had flown similar profiles before, albeit not as long.

The chokes

Breathing difficulties, “the chokes”, are among the most serious effects of sudden decompression. Divers who surface too quickly experience a rapid decrease in gas pressures which can lead to the release of super-saturated nitrogen in the form of bubbles trapped inside tissue. In the more common “bends”, the bubbles are trapped in joint tissue, causing pain upon use of the joint. When reproduced in experimental animals, the chokes reveal nitrogen bubbles trapped in pulmonary arteries, leukocytes surrounding them, then development of lung edema.

I contacted medical personnel at the closest facility with a hyperbaric chamber to discuss this possible diagnosis and to see if they thought recompression would be appropriate in my case. As we talked through the history of my symptoms, it quickly became clear that it was not the chokes. My decompression from sea level to FL230 had occurred slowly and resulted in no symptoms at altitude. My recompression had already occurred in the descent for landing days before. 

It was now over a week since I first showed the symptoms of “shortness of breath” on exertion, pushing the airplane into the hangar in Oklahoma. That was before the high altitude legs. I had been in relatively good condition immediately before the appearance of that symptom. It was getting progressively worse, not better. I was beginning to notice my nailbeds turning pale with mild exertion, such as slowly climbing a gentle hill. I sometimes had to sit down to get my respiration rate to slow down after climbing stairs. Something had changed radically and was continuing to change.

Deep vein thrombosis (DVT)

In DVT, clots form in the veins of the legs, most commonly in the calves, and most commonly in the left leg. One theory for the higher frequency in the left leg cites the routing of the left common iliac vein behind the right common iliac artery, where it can be compressed against the lumbar spine. This phenomena and theory are referred to as the May-Thurner Syndrome, in honor of R. May and J. Thurner, who first described it in 1957.

Eight years previous I had been diagnosed and treated for deep vein thrombosis (DVT) in my left leg. My recovery appeared to have been complete. There had been no recurrence of swelling in the leg. The presumed cause had been determined to have been very long flight legs in a survival suit, while limiting fluid intact; I had subsequently been persuaded to stop doing the transatlantic flights that required those conditions. In addition, in the years immediately following the DVT, I had been careful to keep hydrated on longer flights, to move my legs regularly, and to watch for any signs of swelling. As time passed with no sign of recurring problems, I had grown lax, limiting fluid intake on long legs to avoid the need to urinate and failing to move my legs regularly. 

DVT can also lead to complications in the legs referred to as chronic venous insufficiency (also known as post-thrombotic syndrome). This condition is characterized by pooling of blood, chronic leg swelling, increased pressure, increased pigmentation or discoloration of the skin, and leg ulcers known as venous stasis ulcer. Since my 2001 DVT, I have had mild post-thrombotic symptoms — splotchy red discoloration on the skin of my left ankle, and occasional soreness in my left calf. But these mild post-thrombotic symptoms had not changed recently, so initially I did not consider my new shortness of breath symptom related to my earlier DVT.

I walked into my internist’s office without an appointment early on the day after Labor Day 2009, having finally decided it was time to seek medical help. I was there before he was. When he came in and heard the symptom, he immediately examined me and ordered an EKG. Judging by a change in the EKG, added to the account I gave him of the flights to and from Oklahoma, he came up with a diagnosis of pulmonary emboli within minutes and ordered an ambulance to take me to the nearest emergency room, where I was put on oxygen and a chest CT scan revealed extensive clots in the pulmonary arteries in both lungs. I was injected with a form of heparin, Enoxaparin sodium (manufactured and marketed by Sanofi-Aventis under the tradename Lovenox), to counter the formation of further clots and allow my body opportunity to begin to clear existing clots. I was also started on longterm warfarin to reduce clotting factors and lower the likelihood of further clot formation. 

Pulmonary emboli

Blood clots that detach from the place where they originate and travel through the circulatory system to lodge elsewhere are termed emboli. If they lodge in the blood supply to the lungs, they are termed pulmonary emboli (singular: embolus). Almost all pulmonary emboli originate in the veins of the legs, where venous pressure is lower and conditions favor clot formation. A doppler scan of the veins in my legs showed the right leg clear of clots, while my left leg showed a new clot behind my knee. An echo cardiogram showed that my right ventricular pressure was 60 mm at rest, instead of a normal 20 mm, revealing the extent to which my heart had been working to overcome the blockage in my pulmonary arteries.


Subcutaneous injections of heparin immediately increase the activity of antithrombin III, which inhibits clotting factors Xa and IIa in the contact activation coagulation pathway formerly known as the intrinsic pathway. Factor Xa in particular is the catalyst for the conversion of prothrombin to thrombin. Inhibiting it therefore reduces thrombin which reduced fibrin formation in clots.


Administered orally, it gradually results in the production of undercarboxylated versions of clotting factors II, VII, IX, and X; these relatively inactive factors are collectively referred to as PIVKAs (proteins induced [by] vitamin K absence/antagonism), and individual coagulation factors as PIVKA-number (e.g. PIVKA-II). Specifically, warfarin acts by inhibits the VKORC1 subunit of vitamin K epoxide reductase, responsible for recycling vitamin K epoxide back to vitamin K and vitamin K hydroquinone.

Because it also negatively impacts the regulatory proteins C, S, and Z, it initially has the undesirable effect of increasing clotting rates, which is an added reason heparin is administered with it initially, especially when warfarin concentrations are being rapidly increased.

Prothrombin time

To gauge the correct dose of warfarin, clot-formation time is measured by exposing a blood sample is to animal tissue. INR (International Normalized Ratio) is the standard used in this measurement, endorsed by the World Health Organization. Normally, without anticoagulants, human INR measures in the 0.8 to 1.2 range. Desired range for anticoagulation therapy is 2.0 to 3.0. Specifically, what is being measured is the tissue factor coagulation pathway, formerly known as the extrinsic pathway, which is impacted by warfarin therapy. Once the desired INR 2.0-3.0 is established, there is little danger of excessive bleeding. A study published in 2007 concluded that in 2004 in the US, there were 30 million warfarin prescriptions and 46 deaths primarily caused by anticoagulation. In the event an antidote is needed to warfarin, in order to increase coagulation rates, Vitamin K and fresh-frozen blood plasma can be administered.


After my bout of DVT in 2001, my internist took me off warfarin after the clots had been resorbed, and suggested a longterm low-dose (81 mg daily) aspirin regimen. I adhered to that for a few years, then stopped. Now that I have suffered a second more serious occurence with emboli, my internist is recommending longterm warfarin therapy. A condensed account of how aspirin interfers with clotting by altering platelets: thromboxane A2 is normally released by platelets to attract other platelets when physiological conditions trigger the clotting reaction; aspirin irreversibly inhibits thromboxane A2 release by inhibiting cyclooxygenase 1 (COX1); the platelets that are inhibited cannot recover normal functioning, therefore clotting will not return to normal until all or most inhibited platelets are removed from circulation and replaced by normal platelets. Other NSIDs also interfer with platelet functioning, but not irreversibly. Therefore they are not useful in longterm hypercoagulation therapy.

Risk factors for DVT and PE

Surgery, hospitalization, advanced age, obesity, infection, dehydration, immobilization, estrogen-containing contraception, tobacco use; prolonged air travel can combine dehydration and immobilization.

Cause of deaths with PE

The immediate mechanism of death is commonly suffocation or heart failure. A common misconception is that pulmonary emboli can cause stroke. The reverse is true. Clots that originate in the brain can sometimes break free and travel to the lungs, where then can result in sufficient blockage to circulation to result in death.

FAA requirements

FAA regulations and requirements related to my second class medical certificate: unless and until my lungs are clear of clots and my warfarin therapy stabilized, I will not be acting as pilot in command or other required pilot crew member, in compliance with Title 14 CFR, section 61.53, Prohibition on Operations During Medical Deficiency.

By the time of my next pilot’s medical examination, the FAA is going to need see information on family history of thrombotic disease. My father died of heart failure in 1980 at age 67, several years after being diagnosed with congestive heart disease. He had had rheumatic fever at age 13, and likely had mitral valve damage as a result. I rarely saw him in shorts, and rarer still sockless. But when I did, I remarked on the shiny red skin on one or both ankles, often with raw ulcers. It is likely these were post-thrombotic symptoms of undiagnosed DVT and/or PE.

The FAA will want to see recent tests on levels of protein S and C, which are essential components in the normal anticoagulation cycle that keeps unwanted blood clots from forming. Activated protein C (APC) in particular inactivates clotting factor Va, slowing the clotting process. If testing shows APC is not functioning normally, then the FAA will request testing for the factor V Leiden gene mutation, which is usually the cause of this abnormality. It is named after the city Leiden in The Netherlands, where it was first identified in 1994. These tests are typically performed several months after a thrombotic event such as the PE I just experienced. I will need to be taken off warfarin temporarily to allow the tests to accurately show concentrations and effectiveness of protein S and C. 

Looking ahead

For the time being, I will be taking warfarin orally in sufficient doses to keep my INR in the desired 2.0-3.0 therapeutic range, checked regularly by my internist, and potentially self-tested on a device such as the InRatio2 by HemoSense. In the longer term, testing is been done on a class of drugs called direct thrombin inhibitors that promise improvement in dose-determination, monitoring, and interaction with food and other drugs. They also generally have a lower half-life than warfarin, permitting easier restoration of hemostatis when required.

One such drug, Ximelagatran, initially showed good efficacy compared with warfarin, but recently development was stopped by manufacturer AstraZeneca because of reports of liver enzyme derangements and liver failure. Dabigatran is under development for similar indications. Recent studies have indicated Dabigatran is slightly more effective than warfarin.

I will renew my lost dedication to limiting long flight legs. When necessary, I will be careful to move my legs and contract my calves regularly, getting up and moving around the cabin when practical, and drinking adequate fluids. I plan to experiment with a Texas (condom) catheter as a possible means to easier urination in a cockpit environment. It may be advisable to do regular doppler scans of my legs to monitor for new clot formation, especially since there were no observable symptoms in my left leg this time, though a new clot had formed.