http://www.nytimes.com/2002/04/02/health/02BLOO.html

April 2, 2002
 

Technique May Improve Safety of Donated Blood

By ANDREW POLLACK

 
Peter DaSilva for The New York Times

Dr. Stephen T. Isaacs of the Cerus Corporation says of his company's technique to decontaminate blood products: "No matter what the bug is, you can kill it without even knowing it's there.'' The process, called pathogen inactivation, is in a final phase of testing.

 


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A new process now undergoing final testing may rid donated blood of virtually all viruses and bacteria, bringing a new level of safety to blood transfusions.

Experts say the process, which uses chemicals that gum up the genetic material of germs, could eliminate the rare cases of AIDS transmission through transfusions that are not already caught by testing blood and screening donors.

Perhaps more important, it could eliminate any other germs, including ones that have not yet been identified.

Had the process been in use 25 years ago, it could have stopped the spread of AIDS through blood transfusions even before scientists had identified the virus that caused the disease.

"No matter what the bug is, you can kill it without even knowing it's there," said Dr. Stephen T. Isaacs, president of Cerus Corporation, the company based in Concord, Calif., that is the leader in developing the technique, called pathogen inactivation.

Cerus hopes to win approval to use its technique on platelets, one component of blood, in the next few months in Europe, where its first clinical trials were begun.

The company also hopes for approval in the United States for platelets by early next year, and for plasma, another component, late in 2003. In addition, Cerus's goal is to win approval to treat red blood cells, which are used in a majority of transfusions, by late 2004 or 2005.

Transfusion experts, however, have mixed views about the technique.

"This technology is tremendously attractive from a blood safety point of view," said Dr. Lawrence Tim Goodnough, a professor at Washington University in St. Louis and director of transfusion services at Barnes-Jewish Hospital.

But he and others also worry that the technique will sharply raise the cost of blood and that the need for the technique is diminishing as new tests are added to further ensure safety.

The Food and Drug Administration has recently approved a new test that reduces the chances of getting infected with H.I.V. or the hepatitis C virus through a transfusion to about 1 in 2 million.

"The technologies are going to be very expensive and the capacity of hospitals and blood centers to support implementation of these technologies financially is going to be a big issue," said Dr. Michael P. Busch, vice president for research at Blood Systems, the second largest collector of blood, behind the American Red Cross.

Cerus and its competitors will also have to prove to the Food and Drug Administration that their process does not introduce new risks that may be greater than the risk of infection that pathogen inactivation would eliminate.

"One of the things we will have to be certain of is that we are not trading a very tiny risk of viral infection for another risk of adding chemicals to the blood," said Dr. Jerry Squires, chief scientific officer of the American Red Cross, which supplies half the nation's blood.

Pathogen inactivation takes advantage of the fact that the parts of the blood that are given in transfusion — red cells to carry oxygen, platelets to help blood clot and plasma for clotting and other purposes — do not contain DNA or RNA, the basic genetic material of life. But bacteria and viruses do. So knocking out DNA or RNA could kill pathogens while, in theory at least, leaving the blood itself unharmed.

Cerus developed a chemical that, when exposed to ultraviolet light, binds to the genetic material. The bonds prevent the two strands of DNA's double helix from unzipping, thereby preventing germs from replicating. RNA, the genetic material in H.I.V., is immobilized in a similar way. Cerus has shown in laboratory studies that its process can eliminate a wide variety of pathogens,

The company was started in 1991 by Dr. Isaacs, a chemist at the nearby University of California at Berkeley who was working on substances that bind to DNA. He met Dr. Laurence M. Corash, a hematologist who had moved to the University of California at San Francisco in 1982, as the AIDS crisis was starting.

"Basically all my hemophiliac patients got H.I.V.," said Dr. Corash, who began searching for a way to clean blood. He is now Cerus's vice president for medical affairs.

Cerus is working with Baxter International, the giant blood products company. Their main competitor is V.I. Technologies, known as Vitex, of Watertown, Mass., which is working with Pall Corporation, a manufacturer of blood filters. Vitex is concentrating on red blood cells and hopes to start the final stage of clinical trials, putting it a little behind Cerus, which is now starting its red cell trials.

Even after pathogen inactivation is approved, experts say, blood will continue to be tested for viruses, and donors will continue to be questioned about their travels and medical conditions, to provide redundant safety measures.

Some experts say they are not convinced that Cerus's technique can completely kill viruses presented in high amounts. Pathogen inactivation will also not be expected to work against prions, which cause mad cow disease and its human equivalent, variant Creutzfeldt-Jakob disease. That is because prions are proteins and do not have DNA.

The biggest hurdle for approval is likely to be safety. If the chemicals bind to the DNA of pathogens, they may also bind to DNA in patients getting the transfusion.

Cerus's platelet system uses a synthetic chemical known as a psoralen. Psoralens are found naturally in citrus fruit, so they are generally considered safe. But there is evidence that some of them can cause cancer. Cerus said its chemical did not cause cancer when tested extensively in mice that had been genetically engineered to develop tumors easily.

Cerus uses a different chemical for red blood cells because light cannot penetrate these cells to activate a psoralen. Vitex uses a chemical it called Inactine, which it has not described publicly. Gambro, a Swedish company, is developing a system that uses vitamin B2, which is already consumed by people. Gambro has not yet started clinical trials.

For extra safety, Cerus and Vitex require users to remove the chemicals from the blood before it is transfused.

"The only thing we want to add back to a patient is a red cell," said Dr. Bernadette L. Alford, executive vice president of Vitex.

Cerus's platelet process uses a chain of three transparent plastic bags connected by tubes. The donated platelets are put into the first bag, where they comes in contact with the psoralen. They drip into the second bag, which is placed in a machine that looks like a photocopier to expose the platelets to light for about three minutes. The platelets then drip into the third bag, where an absorbent material removes the psoralen.

The companies will also have to show their processes do not harm the ability of the blood cells to do their jobs.

Cerus's clinical trial showed that some platelets were lost in the treatment and that the ones that were transfused did not last as long in the patient as untreated platelets. But while that meant more platelets were used and transfusions were done more frequently, it did not affect the health of the patients, said Dr. Jeffrey McCullough, a professor at the University of Minnesota, who led the clinical trials and is on Cerus's scientific advisory board.

Cerus's process has so far been tested only on platelets collected by a machine made by Baxter, its partner. The company plans to move quickly, however, to prove it works for all platelets.

The technique is expected to add about $50 to $100 to the cost of a unit of blood. Platelets now cost from $200 to $600 and red cells $100 to $200.

Hospital blood centers are already struggling to keep pace with increases in the cost of blood because of new tests and a new technique for filtering out white blood cells, which can cause problems in some transfusion recipients.

Scientists say the technique will clearly improve the safety of platelets, which are stored at room temperature and therefore are prone to bacterial contamination.

Such bacteria kill about 8 to 12 people a year, according to F.D.A. statistics.

Red blood cells are refrigerated so that bacteria are less of a problem. Still, numerous other possible infections exist. These include hepatitis B and other forms of hepatitis. Chagas' disease, which is widespread in Latin America, can fatally damage the heart after many years. Babesiosis, a sometimes fatal tick-borne infection, is found in southern New England and has symptoms similar to malaria. But it is unclear how often such infections are spread through blood transfusion, and many people can fight off the infections.

The biggest benefit of pathogen inactivation may be the insurance it provides against a new pathogen that could appear as H.I.V. did.

"I can tell you as I sit here today that if an agent like H.I.V. emerged next week, we would not be in any better position to deal with it now than we were in 1982," said Dr. Harvey G. Klein, head of the department of transfusion medicine at the National Institutes of Health.

So far, he and others said, the American public has been willing to spend whatever it takes to eliminate even marginal risks of infection. That factor, plus fear of being sued, make it highly likely that pathogen inactivation will be widely adopted.

"I think from a public policy point of view," said Dr. McCullough of Minnesota, "it's almost impossible to be the leader of a major blood program and face the cameras and face the public and say, `I intentionally made a decision to allow people to be infected by blood transfusions because I didn't want to spend the money to prevent it.' "

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