By: Prof. Benjamin Brenner, Director, Thrombosis and Hemostasis Unit, Institute of Hematology, Rambam Medical Center
Hadas Goshen, Clinical Research Coordinator, Thrombosis and Hemostasis Unit, Rambam Medical Center

The airplane has landed. In a moment, it will come to a complete stop. You are already looking \under the seat for the shoes you took off a few hours ago, at the beginning of the flight. All around you, people are already standing up with bags in hand, ready to deplane, while you are still fighting your shoes, which suddenly don’t fit your feet. This can happen to each of us, and no - it’s not because of the shoes. It’s your feet, which, because of edema, have swollen during the flight. Passengers on long haul flight are at risk to develop thrombosis which can be a life-threatening condition. This phenomenon is called “economy class syndrome”.

“Economy class syndrome”

The term “economy class syndrome” derives from the description of a situation characterized by
sitting for a long time, with the legs bent, in an airplane’s crowded economy class. Sitting in this position increases the risk of blood clot formation in the veins of the legs. The longer the flight, the more the risk is increased.
The life-threatening event does not always occur immediately during the flight, but several hours, days or even weeks after the flight.

What is deep vein thrombosis?

The coagulation mechanism acting in our body is based on a system of balances and brakes. Disruption of the balance between the procoagulant and anticoagulant factors can lead to a state of uncontrolled hypercoagulability, which is liable to lead to occlusion (thrombosis) of blood vessels by a blood clot (thrombus).
Deep vein thrombosis in the upper and lower extremities is known as DVT. The blood vessels blocked in hypercoagulable states are the veins, mostly in the legs. A clot is formed, which grows larger and longer along the vein in the limb.
If adequate treatment is not provided to stop this process, there is a risk of detachment of a fragment from the edge of the clot, leading to the formation of an embolus. When the clot carried by the blood flow gets “stuck”, occluding a blood vessel supplying a vital organ (e.g. lungs, heart or brain), a life-threatening condition occurs.

What are the symptoms of deep vein thrombosis?

Redness, swelling, pain and difficulty moving the affected limb.

How is thrombosis diagnosed?

 Ultrasound - the most reliable and convenient test.
Venography - a contrast medium is injected, which demonstrates the veins of the suspected limb in an X-ray. This test is considered to be most reliable, but it is hardly used today due to the availability and convenience of the ultrasound tests. 
D-dimer - a blood test of fibrin degradation products (the natural anticoagulant produced in the liver).  Recently, a new test has been added, called the global protein C (ProC Global) test, which detects abnormalities in the pathway of the natural anticoagulant protein C. (Abnormalities in this pathway tip the scale towards excessive coagulation.)

Risk factors for deep vein thrombosis

Not only prolonged flights can cause deep vein thrombosis. There are three risk factors:
1. Venous stasis - due to immobility (for example, due to paralysis or prolonged immobility following 
surgery or during a long flight).
2. Predisposition to hypercoagulability - during pregnancy, use of contraceptive pills, use of artificial hormones during menopause, hereditary or acquired coagulation disorders, and some types of cancer.
3. Blood vessel injury - due to medication, blood vessel disease, venous catheter or trauma.

What is the reason for edema during prolonged flights?

Just as water doesn’t flow as well in a bent pipe, the same thing happens when a person is in a seated position, which prevents normal blood flow from the legs to the heart, because the blood vessels are bent.
The special climate conditions on airplanes, characterized by dry air, low air pressure and low oxygen levels, increase coagulability. In addition, passengers usually don’t drink sufficient amounts of liquid as required to balance the fluid loss. The dryness increases blood viscosity and is another contributing factor towards the formation of clots during flights.

How do we prevent edema during the flight?

Correct behavior during flights will help to prevent the formation of blood clots:
1. Drink a lot of water and avoid alcohol consumption.
2. Get up and walk around every two hours, that is, at least once during a flight to Europe and four to five times during a flight to the US, South Africa or the Far East.
3. Activate your leg muscles by alternately contracting and relaxing them.
4. For travelers with known risk factors, such as a history of DVT, elastic socks are recommended.
5. For travelers with known risk factors, it is recommended to consult a specialist on coagulation disorders, with respect to suitable preventive anticoagulant therapy.

How is thrombosis treated?

Predisposition to hypercoagulability, detected in laboratory blood tests, is called thrombophilia.
Anticoagulant therapy stops the thrombus growth process, prevents the formation of additional blood clots and enables the natural fibrinolytic system to act to disperse the clot.
Three anticoagulant drugs are currently in use:
“Heparin” - administered by continuous intravenous infusion over days or even weeks, and requires hospitalization.
“Low molecular weight heparin” (clexane, fragmin) - administered by subcutaneous injection, and if long term therapy is required, the patients can treat themselves at home.
“Coumadin” - the most common anticoagulant therapy; administered orally in tablets.

How long does the treatment last?

Since there are also risks associated with anticoagulant treatment, it is usually not given for life, but for several months (at least 3 months) up to several years, in cases of recurrent DVT.
Following termination of the anticoagulant treatment, there is a 4 to 5 percent per year risk of recurrence.

Hypercoagulability and pregnancy

The research team at the Thrombosis and Hemostasis Unit of the Rambam Medical Center, headed
 by the author of these lines, has proven the connection between hypercoagulability and recurrent miscarriages, and has also found the way to prevent them

1-3% of all pregnant women suffer from recurrent miscarriages. The breakthrough in the research and prevention of unexplained recurrent miscarriages occurred only during the last seven years. The research team at the Thrombosis and Hemostasis Unit of the Rambam Medical Center, headed by the author of these lines, succeeded in demonstrating that most of the women suffering from recurrent miscarriages are predisposed to hypercoagulability (they have thrombophilia).
Another Israeli group, headed by the late Prof. Amiram Eldor, from the Ichilov Medical Center, has shown that thrombophilia accompanies late pregnancy complications as well, e.g. preeclampsia, placental abruption, intrauterine growth retardation and fetal death in utero.
After the connection was proven between thrombophilia and recurrent miscarriages, the way to prevent them was also found, using anticoagulant treatment with “low molecular weight heparin” enoxaparin (lovenox, clexane) during the entire pregnancy and the perinatal period. At present, this treatment is not used as well as worldwide.
It is recommended to consult a coagulation specialist with respect to the ways of reducing the risks for pregnancy complications in pregnant women with thrombophilia.

Additional risks for women

If you take oral contraceptive pills (hormones), or receive postmenopausal hormone replacement therapy, and you also have thrombophilia and also smoke, your risk for CVA (stroke) is 100-200 times higher, as compared to the general population.

The tests for hypercoagulability should be performed once in a lifetime, at as young an age as possible. These are tests of:
• Global protein C
• Prothrombin mutation
• Homocysteine level

If the results of some of these tests are positive, additional tests are required for further evaluation.
For your information, this test is performed as part of the screening tests in the Center of Preventive Medicine, Rambam Medical Center.

Who is included in the risk groups for hypercoagulability:

• Men and women with a family history of thrombotic events
• Women with a history of recurrent miscarriages or pregnancy complications
• Women receiving hormone replacement therapy - HRT
• Recommended for women before starting treatment with contraceptive pills
• People who fly frequently and/or fly long distances