NoBlood

Jan B. Wade · #1 (**permalink**) 01-15-2004, 09:23 PM

Posted on Sun, Dec. 14, 2003

Dallas ER doctors hope to test blood product derived from bovines

BY SHERRY JACOBSON
The Dallas Morning News

DALLAS - (KRT) - "Right now, we get you to the hospital and get you a blood transfusion," says Dr. Paul Pepe, chairman of emergency medicine at the University of Texas Southwestern Medical Center at Dallas and Parkland hospital. "Unfortunately, a lot of people don't make it."

So Pepe and his colleagues have been searching for a treatment that could be administered inside an ambulance to stop the life-threatening effects of extreme blood loss. They have ruled out the possibility of paramedics giving such a patient an immediate blood transfusion because it takes too long to determine a person's blood type, not to mention the fact that ambulances don't carry around highly perishable human blood on the off chance that someone will need it.

So the doctors envisioned a blood product that didn't need to be refrigerated, didn't require blood typing and could be readily used in emergency situations. They knew that several companies were racing to develop such blood substitutes for trauma patients.

Then the doctors heard about Hemopure, a substitute that is under review by the U.S. Food and Drug Administration for use by certain surgical patients. The product is derived from the blood of cattle, and is manufactured by Biopure, a Massachusetts company that has been developing blood products for almost 20 years.

"It doesn't require refrigeration; it doesn't require blood-typing; it's cheaper than real blood; and it's completely clean," Pepe says, counting off the purported benefits on his fingers.

But it was the way that this blood substitute works that made the Parkland doctors want to study it further. Hemopure is composed mainly of hemoglobin, or molecules from red blood cells. Flushed through the circulatory system of animals in clinical studies, hemoglobin readily picked up oxygen molecules and delivered them to tissue and organs, the same way a red blood cell would. The lack of cell coating meant that hemoglobin carried no blood type. (Normally a blood cell carries the type, but the molecules inside do not.)

The Parkland doctors say they immediately saw something that could work in a trauma setting.

"People die in the field because they don't have enough blood to carry oxygen to their tissues," explains Dr. Joseph Minei, associate professor of surgery at University of Texas Southwestern and a trauma surgeon at Parkland.

If a study is approved, such a blood substitute could be used only to keep bleeding patients alive long enough to get to the hospital and receive standard care.

Pepe and Minei have written a proposal for testing Hemopure on trauma patients in Dallas and several other cities. They are collaborating with researchers at the U.S. Naval Medical Research Center, which already has committed at least $4 million to the project. The study could get under way next year.

The Navy's interest is similar to that of emergency room doctors.

"When we send sailors and Marines into harm's way, we owe them the best possible combat casualty prevention, care and management," Capt. Richard B. Oberst of the Navy's Medical Service Corps said when the research effort was announced nine months ago.

Officials at Biopure hope to meet soon with the FDA to discuss a possible test of Hemopure on trauma patients, although the agency has not responded to the request yet, says Douglas Sayles, the manufacturer's director of communications.

In August, the FDA completed its review of Phase 3 clinical trials on the surgical use of Hemopure for orthopedic patients who suffer from anemia. But the agency has asked for more information about those studies, a request that could take months to complete.

An FDA spokeswoman said she could not comment on the status of any Hemopure studies.

In its proposal to study the blood product for trauma use, Biopure is hoping to build on previous animal and human studies.

A 2001 review article by Minei and Dr. Brett Arnoldo, associate professor of surgery at UT Southwestern, predicted that there would be a large market for hemoglobin-based oxygen carriers, including trauma care. The study, published in the journal Current Opinion in Critical Care, speculated that it would take three to five years to get such a product on the market.

"We know that our product is well-tolerated in humans and animals," Sayles says, referring to clinical studies that were done in South Africa, where the drug was approved two years ago for use in patients with anemia undergoing orthopedic surgery.

Minei says early versions of hemoglobin-based blood products were found to cause kidney damage, but "the solutions are safer now," he says.

Oxyglobin, a similar blood substitute manufactured by Biopure, was approved five years ago in the United States and Europe for use in dogs that have anemia, a common condition in animals related to blood loss. Since then, the blood substitute has been used in 37 species of animals, including cats, birds and horses.

"Blood is not readily available in veterinary medicine," Sayles notes.

How is it that blood from cattle can be tolerated in humans and other species? Sayles says, "Purification is the key." But the company's purification process is "proprietary information," he adds.

"We've learned over the years that these oxygen therapies have a different physiology in the body than blood does," he says. "Blood is thicker than water. Ours is more like water."

If the trial of the product is approved by the FDA, the Parkland researchers hope to attract up to 1,000 patients to their national study. One unusual feature is that not all of the participants would be able to give informed consent.

"Some of them could be unconscious," Pepe says. "Traditionally, you follow a lengthy process of informing the patient about the drug you're studying, including possible side effects. That won't necessarily be possible here."

Instead, the doctors say they recently have begun a "community discussion" on the possibility of staging this blood study in Dallas. Already they have contacted organizations and the news media about how it might work.

Although the protocols, or rules for the study, have not been written yet, Pepe says it is likely that the blood substitute would be used only on critically injured patients whose blood pressure is dropping, a possible indication of excessive, life-threatening bleeding. People with such injuries would have a 50-50 chance of being a participant if they met the study's criteria. The blood product would be used on one day, and traditional care the next to provide a comparison, or control group.

It might be possible, though, to develop an identification system for those who might object to being given artificial blood - perhaps a wristband or a decal on the car, Minei says.

But Pepe predicts there would be no outcry against the study.

"When I think about a study like this, I ask myself if I or a member of my family would enter it," he says. "The answer is yes."