Drug stops the bleeding -- but does it also stop lives?

American military doctors in Iraq have injected more than 1,000 wounded troops with a potent and largely experimental blood-coagulating drug despite mounting medical evidence linking it to deadly blood clots that lodge in the lungs, heart and brain.

The drug, called Recombinant Activated Factor VII, is approved in the U.S. for treating only rare forms of hemophilia that affect about 2,700 Americans. In a warning last December, the Food and Drug Administration said that giving it to patients with normal blood could cause strokes and heart attacks. Its researchers published a study in January blaming 43 deaths on clots that developed after injections of Factor VII.

The U.S. Army medical command considers Factor VII a medical breakthrough in the war, giving physicians a powerful way to control bleeding that can be treated otherwise only with surgery and transfusions. Guidelines at military field hospitals encourage its liberal use in all casualties with severe bleeding, and doctors in Iraq routinely inject it into patients upon the mere anticipation of deadly bleeding.

“When it works, it’s amazing,” said Col. John B. Holcomb, an Army trauma surgeon and the service’s top advisor on combat medical care. “It’s one of the most useful new tools we have.”

Yet the Army’s faith in the $6,000-a-dose drug is based almost entirely on anecdotal evidence and persists despite public warnings and published research suggesting that Factor VII is not as effective or as safe as military officials say.

Doctors and researchers at civilian hospitals, including major medical centers such as Johns Hopkins and Massachusetts General, have largely rejected it as a standard treatment for trauma patients. Other hospitals say they have grown increasingly cautious about administering it because of clots found in their patients, including some that have caused deaths.

Meanwhile, doctors at military hospitals in Germany and the United States have reported unusual and sometimes fatal blood clots in soldiers evacuated from Iraq, including unexplained strokes, heart attacks and pulmonary embolisms, or blood clots in the lungs. Some have begun to suspect Factor VII.

At the Walter Reed Army Medical Center in Washington, D.C., doctors said they tried to determine last year whether a seemingly high incidence of blood clots in their patients was related to Factor VII use in Iraq. But they found that the Army was not collecting sufficient information about its use of the drug to draw any conclusions.

Doctors at the Landstuhl Regional Medical Center in Germany said they planned to track complications among war casualties who got Factor VII, after concluding that a heart attack in a patient in August was probably caused by the drug.

During one 24-hour period in May, while journalists for the Baltimore Sun were at the 10th Combat Support Hospital in Baghdad, three U.S. Army soldiers arrived in the emergency room with traumatic injuries, and all of them were injected with Factor VII. Two subsequently died, not from their battlefield injuries but from complications related to blood clots, according to medical records and interviews with doctors.

Some trauma and blood specialists outside the armed services think the military is taking an unwarranted risk with wounded soldiers because the drug has never been subjected to a large-scale clinical trial to verify that it works and is safe for patients without hemophilia.

“It’s a completely irresponsible and inappropriate use of a very, very dangerous drug,” said Dr. Jawed Fareed, director of the hemostasis and thrombosis research program at Loyola University in Chicago and a specialist in blood-clotting and blood-thinning medications.

Army trauma specialists say that blood clots in severely injured patients can have many causes and that using Factor VII is worth the risk.

But some civilian doctors who have worked with the drug say its clotting capabilities are so profound that they have to assume it is responsible for deaths among military casualties who have received it.

“Of course some of them are dying from it,” said Dr. Louis M. Aledort, a professor of hematology at the Mount Sinai School of Medicine in New York who specializes in clinical research and who has studied Factor VII safety. “If you give people this kind of dangerous coagulating product, some of them are going to have [blood clots].”

Deciding what rate of complications is acceptable is a decision generally left to individual doctors. Officials at Novo Nordisk, the drug’s manufacturer, say evidence of clot-related complications doesn’t mean that Factor VII is too dangerous to use, only that the side effects need to be weighed against its potential to help a patient.

“It’s really not a question of an absolute safety level, but rather a ratio of benefit to risk that has to be established,” said Dr. Michael Shalmi, a Novo Nordisk vice president.

Military officials are unapologetic about moving aggressively toward a new treatment for the types of deadly bleeding they see frequently in Iraq. Wounded troops requiring transfusions of 10 or more units of blood have a 25% to 50% chance of dying from their injuries, they say, so anything that helps to stop severe bleeding is worth exploring.

“We’re making decisions, in the middle of a war, with the best information we have available to us,” said Holcomb, commander of the Army’s Institute of Surgical Research.

Military doctors say they’ve gathered enough hands-on evidence of the drug’s effectiveness to continue promoting its use.

“I’ve seen it with my own eyes,” said Air Force Lt. Col. Jeffrey Bailey, a trauma surgeon at the American military hospital in Balad, Iraq. “Patients who are hemorrhaging to death, they get the drug and it stops. Factor VII saves their lives.”

But in the hospitals away from the front lines, military doctors tell anecdotes about patients with strange clots in their lungs or brains that defy obvious clinical explanation. Factor VII has become a prime suspect.