Team Infidel
Forum Spin Doctor
Baltimore Sun
November 19, 2006
Pg. 1
Military doctors in Iraq say that Factor VII saves wounded soldiers, but other doctors and medical research suggest that it can cause fatal clots
By Robert Little, Sun Reporter
BAGHDAD--American military doctors in Iraq have injected more than 1,000 of the war's 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 affecting 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 to be a medical breakthrough in the war, giving frontline physicians a powerful new means of controlling bleeding that can only be treated otherwise with surgery and transfusions. They have posted guidelines at military field hospitals encouraging its liberal use in casualties with severe bleeding, and doctors in Iraq routinely inject it into patients upon the mere anticipation of deadly bleeding to come.
"When it works, it's amazing," said Col. John B. Holcomb, an Army trauma surgeon and the service's top adviser 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 Hospital, have largely rejected it as a standard treatment for trauma patients. Other hospitals studying Factor VII, including the R Adams Cowley Shock Trauma Center in Baltimore, 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. And 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 discovered 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 plan to track complications among war casualties who got Factor VII, after concluding that a heart attack in a patient last August was likely caused by an injection of the drug in Iraq.
During one 24-hour period in May, while journalists for The 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.
'Irresponsible, inappropriate'
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.
"It's insane, using it that way. Absolutely insane," said Dr. Rodger L. Bick, a University of Texas hematologist and editor of the Journal of Clinical and Applied Thrombosis/Hemostasis.
Army trauma specialists say that blood clots in severely injured patients could be caused by many things and that using Factor VII is worth the risk, considering reports from military doctors in Iraq describing its success at controlling severe bleeding.
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 the large group of 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]."
Yet he and other civilian specialists were less troubled by the potential dangers, which they said might be justified, given the severe injuries in Iraq, than by the lack of scientific evidence that war casualties are getting any benefit for taking the risk.
"If you don't have that," Aledort said, "then you're just experimenting on people with a dangerous drug."
'Benefit to risk'
Deciding what rate of complications is acceptable is generally left up 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 bleeding 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, vice president of biopharmaceuticals for Novo Nordisk.
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 percent to 50 percent chance of dying from their injuries, they say. And so anything that helps to stop severe bleeding is worth exploring, they say, even if it carries risk.
"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."
As the trauma adviser to the Army surgeon general, Holcomb is largely responsible for establishing what types of drugs and equipment are used to treat wounded American soldiers. It was his decision, with the support of Army leadership, to begin using Factor VII as a standard treatment in Iraq.
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.
November 19, 2006
Pg. 1
Military doctors in Iraq say that Factor VII saves wounded soldiers, but other doctors and medical research suggest that it can cause fatal clots
By Robert Little, Sun Reporter
BAGHDAD--American military doctors in Iraq have injected more than 1,000 of the war's 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 affecting 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 to be a medical breakthrough in the war, giving frontline physicians a powerful new means of controlling bleeding that can only be treated otherwise with surgery and transfusions. They have posted guidelines at military field hospitals encouraging its liberal use in casualties with severe bleeding, and doctors in Iraq routinely inject it into patients upon the mere anticipation of deadly bleeding to come.
"When it works, it's amazing," said Col. John B. Holcomb, an Army trauma surgeon and the service's top adviser 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 Hospital, have largely rejected it as a standard treatment for trauma patients. Other hospitals studying Factor VII, including the R Adams Cowley Shock Trauma Center in Baltimore, 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. And 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 discovered 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 plan to track complications among war casualties who got Factor VII, after concluding that a heart attack in a patient last August was likely caused by an injection of the drug in Iraq.
During one 24-hour period in May, while journalists for The 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.
'Irresponsible, inappropriate'
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.
"It's insane, using it that way. Absolutely insane," said Dr. Rodger L. Bick, a University of Texas hematologist and editor of the Journal of Clinical and Applied Thrombosis/Hemostasis.
Army trauma specialists say that blood clots in severely injured patients could be caused by many things and that using Factor VII is worth the risk, considering reports from military doctors in Iraq describing its success at controlling severe bleeding.
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 the large group of 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]."
Yet he and other civilian specialists were less troubled by the potential dangers, which they said might be justified, given the severe injuries in Iraq, than by the lack of scientific evidence that war casualties are getting any benefit for taking the risk.
"If you don't have that," Aledort said, "then you're just experimenting on people with a dangerous drug."
'Benefit to risk'
Deciding what rate of complications is acceptable is generally left up 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 bleeding 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, vice president of biopharmaceuticals for Novo Nordisk.
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 percent to 50 percent chance of dying from their injuries, they say. And so anything that helps to stop severe bleeding is worth exploring, they say, even if it carries risk.
"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."
As the trauma adviser to the Army surgeon general, Holcomb is largely responsible for establishing what types of drugs and equipment are used to treat wounded American soldiers. It was his decision, with the support of Army leadership, to begin using Factor VII as a standard treatment in Iraq.
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.