"I want to hear about [the patient's] history, I want to know if they're at risk for thrombotic complications, and I want to know whether more routine measures that are medically appropriate have been exhausted," said Dr. Paul M. Ness, director of the transfusion medicine division at Johns Hopkins Hospital and a "gatekeeper" for Factor VII use there. "The problem is that we haven't seen any kind of good, randomized, controlled study showing us that the drug is safe and that it works."

"I think everyone has an anecdotal experience where it seemed to work dramatically in a patient," said Dr. John M. Harlan, chief of hematology/oncology at Seattle's Harborview Medical Center. "It's just that without the large, randomized trials, you can't identify those patients most likely to benefit. And, obviously, there are questions about adverse complications."

At Shock Trauma

Doctors at the R Adams Cowley Shock Trauma Center in Baltimore have been among the more prominent advocates for Factor VII in trauma patients, publishing several papers about the drug and documenting almost 300 uses since 2001.

When the FDA study questioning the drug's safety was published in January, the Shock Trauma doctors wrote a rebuttal letter and began sifting through their own data, expecting it to show that the potential for complications was overstated.

After reviewing each use at Shock Trauma over the last five years, however, doctors there realized that the data revealed an 8.7 percent rate of major clot-related complications.

Two young patients developed mesenteric ischemia, an interruption of blood flow to the intestines rarely found in patients younger than 60.

A woman developed a clot in the deep veins of an otherwise healthy leg.

One woman died of a heart attack minutes after being injected with the drug, and doctors later found a massive clot in her heart.

The survey identified 12 patients whose deaths were due, in part, to blood clots they suffered after getting Factor VII.

Doctors at Shock Trauma are still exploring Factor VII, but they say they are more cautious about who gets it. They have come to believe that Factor VII can cause cerebral and abdominal blood clots that they don't fully understand and that it should be used sparingly in patients without hemophilia.

"If you'd asked me a year ago, I would have told you the complication rate wasn't anywhere near 8 percent. But the data doesn't lie," said Dr. Thomas M. Scalea, the center's physician-in-chief.

Holcomb said that without a control group for comparison, the Shock Trauma data offers no new perspective on the safety of Factor VII. And he agrees that only a trial where patients are randomly given either the drug or a placebo can determine Factor VII's true rate of complications.

But Scalea thinks his results are "troubling," particularly considering the scarcity of sound research available and the lack of statistical evidence that Factor VII actually works.

"The data is the data, and nobody, to date, has been able to show an increase in survival," said Scalea.

"I think John Holcomb is an incredibly talented, tremendously bright guy who's had experiences I haven't had, and it's very possible that if I worked in John's environment I'd make the same decisions he's making.

"But I've had experiences he hasn't had. And in this environment we've become circumspect about Factor VII, in terms of its cost, its effectiveness and the rate of complications."

'Step back and ask'

The U.S. military has never performed the kind of retrospective analysis that the Shock Trauma center did, because it doesn't have the data available to do it.

Doctors in Iraq, Germany and the United States hold a conference call every Thursday to discuss patients they treated in recent days, in hopes of spotting issues and improving the system.

But with dozens of casualties evacuated from the war zone each week, the information can be overwhelming, particularly given the demanding nature of the work that military medical teams do every day.

When The Sun interviewed Gina Dorlac in late August, she had just awakened from a brief nap after an all-night shift during which nine war casualties were admitted to Landstuhl's intensive care unit. She joked that the workload and the long hours were reminiscent of her residency training. And she equated the perspective on patient care that the pace sometimes affords her to that of looking at the system through a microscope.

"You need someone outside of this kind of setting to be able to step back and ask those questions" about Factor VII, Dorlac said. "I don't know if they're doing that. I hope so."

robert.little@baltsun.com