"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. "We're not waiting" for more clinical research, he said. "We'd still be talking about these things 10 years from now."
The decision was made in February 2004, Holcomb said, after he saw results from the largest clinical trial conducted so far of Factor VII's use in trauma -- an international study of 277 people, sponsored by Novo Nordisk. It concluded that trauma patients who got Factor VII had the same likelihood of suffering blood clots as those who didn't. Those results, and data from a few much smaller studies that did not focus on trauma patients, made Holcomb comfortable that the drug was safe enough, he said.
The same study also suggested that Factor VII doesn't work particularly well in trauma patients -- especially those with penetrating injuries -- but military doctors say they've since gathered enough hands-on evidence of the drug's effectiveness to continue promoting its use. Some say it's the best solution they've found for "coagulopathic" bleeding -- a particularly vexing type of hemorrhage in which a patient oozes blood even after surgical repair of his injuries. Without Factor VII, the only available treatment is blood transfusion, which they say doesn't always reverse the condition and can even make it worse.
"I've seen it with my own eyes," said Air Force Lt. Col. Jeffrey Bailey, a trauma surgeon deployed this summer as senior physician 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."
"I've never seen anyone have a stroke because of Factor VII. I've never seen anyone have a pulmonary embolism because of Factor VII," said Army Maj. Brett Schlifka, a neurosurgeon assigned this year to the Balad hospital. "But I've seen people who survived because of Factor VII."
Doctors in Iraq's emergency rooms, however, almost never care for their patients long enough to see firsthand whether blood clots or other complications have developed. A typical war casualty treated at the hospital in Baghdad is flown to Balad within hours, then to Landstuhl in a day or less, and then to the United States within another three or four days.
"I haven't noticed any complications, but then I wouldn't see them anyway," said Army Capt. David Steinbruner, an emergency room doctor who served at the hospital in Baghdad. "They're usually gone by the next day."
Unwanted clots in the veins, including pulmonary embolism and a precursor called deep vein thrombosis, or DVT, are occasional complications of severe trauma regardless of whether Factor VII is used. And injured soldiers and Marines are particularly susceptible to such clots because they spend hours immobilized and unconscious flying from Iraq to the recovery hospitals in Germany and the United States. Clots in the arteries, which flow outward from the heart and can lead to stroke and heart attack when they are blocked, are much less common.
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 any obvious clinical explanation. And Factor VII has become a prime suspect.
When researchers at Walter Reed studied cases of blood clots in 2003, before Factor VII was introduced in Iraq, they concluded that war casualties had the same frequency of complications as victims of civilian trauma. A year later, the New England Journal of Medicine published a report on military care for the wounded, including the nine-month period after the Army had begun using Factor VII, and this time noted a "startling" rate of pulmonary embolism and DVT.
Doctors at Landstuhl began injecting every battlefield patient with an anti-coagulant drug in early 2005 because of the perplexing incidence of blood clots, and doctors there say that the effort seemed to reduce the rates of pulmonary embolism, DVT and other clots in the veins.
But doctors say they have also seen war casualties in the last two years with unusual clots in their hearts and arteries that resemble complications found in elderly patients -- troubling, given that most patients at Landstuhl are in their 20s or 30s.
"We see some weird strokes," said Lt. Col. Warren Dorlac, director of trauma surgery and critical care at Landstuhl. "You can't draw any conclusions from one patient, but when you start to see [multiple cases], after a while you have to ask if something is wrong."
In early August, doctors at Landstuhl said they were worried by the case of a patient in his early 20s who suffered a heart attack while recovering from combat injuries. Federal privacy laws prohibit release of specific information about the patient, who survived, but doctors said they pored over his records for evidence of heart disease, coronary artery disease or some other explanation. The only thing that stood out was his injection of Factor VII in Iraq.
"He really scared me, because he didn't act the way he was supposed to act. There was no reason in the world why he should have had a heart attack," said Air Force Lt. Col. Gina Dorlac, the director of intensive care at Landstuhl, who treated the patient, and the wife of the hospital's trauma specialist. "The medicine was the only explanation that seemed likely."
Even doctors who suspect a link between Factor VII and clot-related complications in a patient say they can't determine if there is a larger trend because the military doesn't keep enough information to study it.
"To be honest with you, we've never looked, because we don't have the tracking system that covers everything that would be necessary to do that," Warren Dorlac said. "I think it's something we definitely need to look at."