Passengers faced with a choice between a window or aisle seat on a long plane flight might want to opt for the aisle. Several studies have suggested an increased risk of blood clots and their complications from sitting for long periods of time, as in transoceanic flights.

Researchers have been unable to confirm a direct link between air travel and the blood clots, but the evidence is mounting. And physicians say an ounce of prevention may be a good idea.

Although the problem is nicknamed economy class syndrome for the cramped seating in the back of passenger planes, deep vein thrombosis can occur with any activity or occupation that involves long periods of sitting.

The body must work against gravity to return blood from the legs back up to the heart. The calf muscle acts like a pump pushing blood back up through the veins. Walking helps this pumping action.

Sitting for long periods of time limits calf muscle activity. That can lead to congestion or pooling of blood in the leg, particularly for people with damaged or disease valves in their veins.

Passengers may experience swelling or aching of the lower leg. But more importantly, the reduced blood flow can lead to clots that can break off and travel to the heart or lungs, causing an obstruction known as pulmonary embolism. In some cases, the condition can be fatal.

Long flights may involve several factors that conspire to increase risk of developing the clots. Those include long periods of inactivity, compression of the leg vein at the edge of the seat, and possibly dehydration due to decreased fluid intake or excessive use of alcohol during the flight. In a one recent study, all of the subjects that developed blood clots had been in non-aisle seats.

While the risk is higher for passengers on long flights, the overall risk is still relatively low, particularly for otherwise healthy individuals.

A German study in 2003 recruited passengers intending to go on long-haul flights and used ultrasound to compare their leg veins before and after the flights. The study found blood clots in 2.8 percent of the travelers, compared with 1 percent of non-travelers. Most of the blood clots resulted in no apparent symptoms and were confined to calf muscle veins. The study was funded by Aventis Pharmaceuticals, which markets a clot-busting drug as a preventive measure.

The number of passengers who develop the more serious pulmonary embolism is even lower. In 2001, French researchers reviewed the medical records of patients arriving at Charles de Gaulle Airport in Paris who were taken to the hospital because of a suspected pulmonary embolism between 1993 and 2000.

Of the 135 million air travelers over that time frame, there were only 56 confirmed cases of pulmonary embolism. The researchers found that the risk of pulmonary embolism significantly increased after 3,000 miles to 1.5 cases per million, and to 4.77 cases per million passengers for flights greater than 6,000 miles. Only three of 56 stricken passengers reported getting up from their seats during the flight. All 56 affected passengers had flown at least 2,500 miles.

While most studies have found that patients developing blot clots were sitting in more cramped economy class seats, experts say that could be because the vast majority of airplane seats are in the economy section. It is not clear whether passengers in business or first class seats have a reduced risk of blood clots.

The World Health Organization issued a statement saying there was not sufficient evidence to prove a link, but that there is likely a connection. The group said the overall risk is probably small. A comprehensive study sponsored by the health organization is expected to be completed next year.

People at greater risk involve those who are obese or pregnant, or who have chronic heart disease, varicose veins, a history of blood clots, or recent trauma or surgery. Some experts believed athletes, particularly endurance athletes such as marathoners, might be at a greater risk for blood clots as well. According to Airhealth .org, a non-profit, physician-run resource on flight-induced blood clots, 85 percent of those who contact the site after experiencing a blood clot are endurance athletes.

”People with slower resting blood flow are at greater risk of stasis, stagnant blood subject to clotting,” the organization says on its Web site. ”Also, they are more likely to have bruises and sore muscles that can trigger clotting.”

The risk may be even greater when passengers are traveling to have surgery. Prompted by the death of a 37-year-old man who flew 4,800 for surgery and died from a pulmonary embolism, researchers at the Mayo Clinic pulled the records of thousands of their patients with addresses outside North America. They identified more than 3,700 patients who had traveled more than 5,000 miles before their surgery. The travelers had a 30-fold higher incidence of dangerous blood clots or pulmonary embolisms within four weeks of surgery than patients who didn’t traveled as far.

”At medical institutions where patients are traveling a great distance for surgery, physicians should consider it as an additional risk factor for post-operative blood clots in the veins,” says Dr. Juraj Sprung, an anesthesiologist at the clinic who led the study.

There is evidence that wearing below-the-knee elastic stockings during flights can substantially reduce the risk of developing blood clots.

”Gradient compression socks or stockings mimic the function of a water pump that propels water uphill, essentially to counteract the effects of gravity,” says Dr. Anthony Comerota, chief of vascular surgery at the Temple University School of Medicine in Philadelphia. ”By delivering pressure at the ankle that gradually decreases as it extends up the leg, gradient compression hosiery helps assist veins in the movement of blood back to the heart and reduces blood pooling that can cause swollen, fatigued legs that may contribute to the formation of dangerous blood clots.”

Several companies, including Jobst Hosiery and TravelSox, sell compression stockings for air travel.

Last year, the American College of Chest Physicians for the first time offered specific recommendations for long-distance travelers.

”Although prevention is often focused on at-risk patients, such as women who are pregnant or patients who have recently had surgery, we strongly advise all patients traveling on flights of more than six hours to take the necessary precautions to prevent thrombosis,” says Dr. Jack Hirsh, a Canadian physician from Hamilton, Ontario, who headed the panel drafting the recommendations.

For flights longer than six hours, passengers should avoid constrictive clothing around the lower extremities and waist, avoid dehydration and engage in frequent calf-muscle stretching, the group said.

The physicians also backed graduated compression stockings or medications designed to prevent blood clots for higher-risk groups. Aspirin is not recommended for the prevention of travel-related blood clots, the group said.