America: the opec of the global plasma industry

In the spring of 1988, Dr. Carol Kasper began to have problems purchasing Factor VIII, the lifesaving blood-clotting concentrate she uses to treat hemophiliacs.

With it, hemophiliacs can lead relatively normal lives; without it, they can bleed to death from a minor cut.

By fall, as a nationwide shortage of Factor VIII deepened, the supply at the hemophilia clinic that Kasper runs in Los Angeles had dwindled to one- third of usual levels, and she faced a wrenching choice:

Should she save her limited supply of a new, safer Factor VIII for the children, or share it among all 500 hemophiliacs she treats - including many adults already suffering from AIDS?

The children had not yet been exposed to the AIDS virus. But by that time, 60 percent of all adult hemophiliacs in America had become infected, as a result of using clotting factor made from blood plasma contaminated with AIDS.

While the doctor wrestled with her life-and-death decision, U. S.-based manufacturers of Factor VIII were making decisions of their own.

Several companies stopped making Factor VIII as long as three months before introducing their new, safer clotting concentrate; one company raised prices nearly 20 percent at the height of the shortage, and three manufacturers continued to export large amounts to Japan and Europe, where they could charge higher prices.

As a result, America's 20,000 hemophiliacs faced not only a health crisis but a financial one as well - a crisis that continues today, even though the shortage has eased.

The average cost to hemophiliacs soared from about $8,000 a year in 1987 to more than $50,000 a year today. Hemophiliacs who must use large amounts of the clotting medicine pay as much as $80,000 a year.

Manufacturers denied they were profiteering. They cited higher production costs and said that profits from the worldwide sale of clotting factor helped underwrite lower prices paid by Americans.

In many ways, though, their justifications underscored a fundamental tenet of business: Companies will try to sell their products wherever the most profit can be made. That is as true in the blood business as it is in the oil or steel industries.

The buying and selling of blood is a multibillion-dollar business. And plasma, from which many medicines are made, is the most commercial part of the blood business. The plasma industry had sales of more than $2 billion in 1988.

Unlike blood banks, the plasma industry operates on a global scale, is highly competitive and experiences dramatic swings in the availability and price of its products - as with Factor VIII last year.

Plasma and the medicines made from it are bought and sold like other commodities, with decisions made in one country often causing sharp price changes or shortages in other countries.

"It's like selling hog bellies or wheat or beef. It gets sold all over," said Thomas M. Asher, chairman of Hemacare Co., a for-profit company in Sherman Oaks, Calif., that trades in plasma and other blood products.

And if U. S.-based manufacturers choose to sell plasma medicines such as Factor VIII to other countries while there's a shortage here, they are free to do so. The U. S. government makes no attempt to restrict exports of such medicines during shortages to ensure an adequate domestic supply.

When it comes to selling blood, the United States has the most liberal standards in the world for how often a person may sell his own plasma.

Federal regulations allow individuals to sell up to 60 liters a year (nearly 127 pints) of their own plasma - a maximum of two donations a week. That is twice the amount allowed by the next country, Canada. And it is four times the amount - 15 liters a year - recommended by the World Health Organization. (A liter is a little more than a quart. )

Result: More than half the estimated 12 million liters of plasma used in medicines worldwide comes from the United States.

"The U. S. is the OPEC of the plasma business," said Thomas O. Hecht, chairman and chief executive officer of Continental Pharma Cryosan Inc., a Montreal-based distributor of plasma products. "You know what that stands for: the Organization of Plasma Exporting Countries. "

To put the 60-liter figure in human terms, the average American male could each year sell the equivalent of 21 times the amount of plasma in his veins at any given time.

Most of this plasma is collected at the nearly 400 commercial centers that operate nationwide. The centers pay between $8 and $25 for a donation of plasma, which is extracted as whole blood and then put into a centrifuge, which spins out and separates the plasma. The oxygen-carrying red blood cells are then transfused back into the donor.

Many plasma centers offer bonuses to encourage frequent donations. Some advertise special Christmas deals, with the message that selling your plasma is a good way to earn money for Christmas gifts.

While U. S. donors are the source of more than 60 percent of the world's plasma, foreign owners dominate the business. Four of the six largest plasma companies in the United States are owned or controlled by foreign corporations based in Japan, West Germany, Austria and Canada.

JAPAN BUYS THE MOST

These companies collect and buy more than three million liters of plasma in America annually and sell them overseas to other companies, brokers or foreign governments.

They also sell the majority of their plasma medicines abroad. Japan is the single biggest customer, each year importing more than $300 million worth of plasma and plasma medicines. In 1988, 90 percent of plasma products used in Japan were made from blood collected in the United States.

On a per-capita basis, the Japanese use about three times more plasma medicine than either the French or English, according to a World Health Organization report. But Japan collects only about 10 percent from its own donors.

In this international market, it is not uncommon for plasma to change hands several times. Sometimes plasma brokers - middlemen who profit by bringing together those who have plasma with those who need it - are involved.

Even in industry circles, brokers are considered a secretive lot. There are no lists of brokers and finding one is no small task. Locating one willing to talk is even harder.

Asked to describe his business during a brief telephone conversation, one of them, Eric Jarrett, a Woodland Hills, Calif., broker said: "We sell plasma to whoever wants to buy it. "

"No one knows how much they control," said Joseph Rosen, vice president of Sera-Tech Biologicals Inc., a New Jersey company. "One broker may sell to another broker, who again may sell it to me or to a company in Europe. "

Tracking this plasma once it leaves the country is difficult at best, industry officials and government regulators say.

Besides a registration requirement, the federal Food and Drug Administration does not regulate the activities of brokers and does not inspect their operations.

"Whether or not sterility is ever a problem, we do not really know," P. Ann Hoppe, assistant director of the FDA's Division of Blood and Blood Products, told an industry meeting last November. "The storage conditions often are such that bacterial contamination could proliferate if there were any present. So sterility may be less than 100 percent."

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This volatile worldwide system for buying and selling plasma generally works well, industry leaders say.

"It's a very dynamic, interrelated business that has served many persons well," said Robert W. Reilly, president of the American Blood Resources Association, a trade group in Annapolis, Md. "Thousands of hemophiliacs have lived longer and better lives and thousands of other patients worldwide have benefited from products made by the commercial plasma industry. "

Reilly and others also stress that the plasma industry has worked hard in the last decade to clean up its tawdry image by moving many of its collection centers out of inner-city sites into college towns and suburbs.

An increasing number of the newer centers have invested in automated equipment for collecting plasma that is quicker and safer, they say. Some of these centers even have video movies for donors to watch.

"We have intentionally designed the location of our centers to avoid the higher-risk groups," said Jack Luchese, who until recently was an executive of Armour Pharmaceutical Co. in Blue Bell, Pa., a large plasma manufacturer. ''It's all prevention. You start with the right location. You get the right crowd to walk in. You . . . turn down the people who don't fit," Luchese said.

"There is a good side to this industry," said Ralph E. Eacret, president of Associated Bioscience Inc., which operates automated centers in Phoenix and half a dozen college towns. "This is it. "

Not all commercial plasma centers are in college towns or suburbs, though. And not all the clients are as well off as Luchese and others would like.

In Philadelphia, for example, after inspecting the Community Blood and Plasma Center at 1201 Race St., a federal inspector filed a report in April 1988 observing that "there was no soap, hand towels or toilet tissue in the male donor restroom. "

When the inspector asked an official of the plasma center why that was so, the official, M. Dempsey Dudley, said that "given the type of clientele at the facility, it was hard to keep these items in the restroom due to theft," the inspector's report says.

And, along the U. S.-Mexican border, a string of plasma centers attracts thousands of poor Mexicans. Each week they walk, wade or pay a dollar or two to be ferried across the Rio Grande to sell their blood.

There were 22 plasma centers operating along the border in 1988 - more than the number in Chicago, New York and Philadelphia combined.

Depending on your point of view, the centers are either preying upon poor Mexicans or boosting the cross-border economy.

"We are providing a valuable source of income to Mexicans, and it is probably a significant amount of money compared to what they might have gotten elsewhere," said David J. Gury, president of North American Biologicals Inc., a Miami-based company that owns two plasma centers in El Paso.

"It's a throwback to a time when maybe the industry didn't have such a good image," said Anita Bessler, vice president of sales and marketing for Baxter-Hyland Co., a plasma distributor that does not operate a border center. Some critics call this plasma "vampire blood. "

In El Paso alone, there were eight commercial plasma centers operating this summer - one for every 53,125 residents. By comparison, Philadelphia has two - one for every 844,105 residents.

A visit in June to one of Gury's centers found that a majority of the donors were from Juarez, right across the border.

"I don't think it's important that they are coming across the border," Gury said. "The important thing is that the donor meets all of the qualifications as to health and suitability."

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During the early 1980s, many commercial plasma centers were placed in so- called "hot spots" - cities such as San Francisco and Los Angeles that had large populations of gay men. This played a critical, if inadvertent, role in the spread of AIDS into the hemophilic population.

Federal records show that in 1981 - before it was known that AIDS was spread through blood - there were eight plasma collection centers in the San Francisco area and 10 in the Los Angeles area. Some of these centers actively recruited homosexuals because they were considered steady, reliable donors.

In addition, some centers recruited homosexuals who had been exposed to hepatitis because their blood contained hepatitis antibodies, used to make vaccines. Spokesmen for the plasma companies say the plasma from these homosexuals was used only to make the vaccines and did not get into the larger plasma pool used to make Factor VIII.

But at least one expert, Dr. James W. Mosley, believes that by recruiting homosexuals as paid donors, these plasma centers may have contaminated the Factor VIII supply. For, unknown to the plasma collectors, some of these homosexual donors had AIDS and their plasma was used to make Factor VIII, spreading the infection among hemophiliacs who used the clotting factor.

In making Factor VIII, the natural clotting proteins in blood plasma are extracted and concentrated in strength. Clotting proteins from as many as 20,000 plasma donors may be mixed together to form a single batch of the concentrate, increasing the risk that only a few infected donors could contaminate the batch.

While it is not known how many infected donors actually sold their plasma, ''it does not seem unreasonable . . . to suggest that homosexual men became disproportionately represented among paid donors," Mosley told a gathering of experts on hemophilia in March. Mosley is a professor of medicine at the University of Southern California and an expert on blood.

"Under the circumstances described, one would expect that introduction of HIV (human immunodeficiency virus, the AIDS virus) into the homosexual community would be quickly followed by introduction among hemophiliacs treated with (blood-clotting) concentrates," Mosley said.

And that is exactly what happened, data collected by federal officials show.

AIDS was introduced into the hemophilic population around 1979 - shortly after it started to appear among homosexuals. By 1982, an estimated half of all American hemophiliacs had been infected with the virus, although only a small percentage had symptoms of the disease, according to the Centers for Disease Control.

People with AIDS antibodies - that is, those who are infected - do not always exhibit symptoms, though it is now believed that all will eventually come down with the fatal disease.

That same year, an FDA official told the major plasma collectors they should close their centers in high-risk areas. By late 1983, most had been

closed.

But by then it was too late. Federal records show that by December 1983, two dozen hemophiliacs had developed AIDS symptoms as a result of injecting tainted clotting concentrate, and thousands of others had been infected with the virus.

Today, at least 60 percent of American hemophiliacs - 12,000 people - are infected with AIDS, according to Alan P. Brownstein, executive director of the National Hemophilia Foundation. And among those suffering from the severest form of hemophilia - those who need the greatest amount of clotting factor - nearly nine of every 10 are infected with AIDS.

Company documents made public in AIDS-related lawsuits show the industry fought the introduction of a test for detecting hepatitis in blood that also was thought to be effective in identifying groups at risk for AIDS. It is known as the hepatitis B anti-core test.

One study at the time, January 1983, showed that nearly 90 percent of people judged to be at high risk of developing AIDS also tested positive for the hepatitis B-core antibodies. Thus, proponents argued, in the absence of a specific test for AIDS, the B-core test should be used.

But most plasma manufacturers didn't agree. And on Dec. 14, 1983, the evening before an important meeting with FDA officials, they gathered in a hotel room in suburban Washington to devise a strategy to delay requirement of the test, an internal memorandum written by an official of Cutter Biologicals Inc. shows.

"This proposal was one that had been agreed upon by all the fractionators (manufacturers) the previous evening," the Cutter company memorandum summarizing the meeting said. "The general thrust . . . is to provide a delaying tactic for the implementation of further testing. "

The memorandum was written by Steven J. Ojala and was widely circulated throughout Cutter Biologicals, the largest U. S.-based plasma manufacturer, with headquarters in Berkeley, Calif. At the time, Ojala was director for regulatory affairs at Cutter. He now works for a different company in Kansas. He did not respond to telephone messages left with his wife.

The day after the manufacturers' discussion, federal officials agreed to an industry representative's request to form a task force to "study" the test.

Four months later, an industry-dominated advisory panel that included no consumer representatives reported to the FDA that its members were divided on whether the test should be used. The FDA subsequently accepted the position of those who opposed the test.

The anti-core test was rejected despite government and industry data available at the time showing that as few as four infected donors could contaminate an entire year's worth of Factor VIII.

By that time, epidemiologists from the Centers for Disease Control had linked AIDS to 30 cases involving blood transfusions.

Why were the companies opposed to the test?

Testimony before an FDA panel, Cutter internal records and interviews show that there were several concerns. One was that the hepatitis B-core antibody test was not a specific test for AIDS and would eliminate some donors who did not have the disease.

Another reason was the cost of the test - estimated to be $3 - plus the expense of recruiting new donors to replace the blood that would have to be discarded. One plasma manufacturer, not specifically identified in the documents, estimated that implementing the test would cost his company between $350,000 and $2 million a year.

While most of the industry opposed the hepatitis B-core test, at least one company, Cutter Biologicals, was quietly moving ahead to use it, company records show. Cutter is owned by Bayer AG, a German pharmaceutical and chemical company.

"We recommend that the implementation of core testing be accelerated to the maximum degree possible to gain a competitive advantage in the marketplace," a Cutter memorandum says. "We made no mention of our plans to the others (plasma companies). "

The U. S.-based manufacturers also were slow to implement a process for making Factor VIII safer, one in which viruses are inactivated by heating the concentrate for 10 hours or more, FDA and industry documents and interviews show.

A PASTEURIZED VERSION

Behringwerke AG, a German manufacturer, developed a pasteurized version of Factor VIII in 1978 and began to market it in Germany. Behringwerke filed a U. S. patent application in 1980 describing its pasteurization process in detail and obtained a patent a year later.

During this time, most of the U. S.-based manufacturers were experimenting with heat-treated products in their laboratories. But none of these products was introduced until late 1983 - after the majority of hemophiliacs had been infected with AIDS.

"I don't know why we didn't have a product sooner," Luchese said. "All I can say, from what I can see, the knowledge base wasn't at a stage that was considered something to be done. "

Lawyers for hemophiliacs suing manufacturers for negligence contend that once the AIDS crisis had created public pressure for safer clotting factor, the manufacturers were able to develop a heat-treated concentrate within six months.

"There is no reason . . . to not have had pasteurized product on the market by 1980, had reasonable and prudent research and development been used," Thomas Drees, former head of Alpha Therapeutics Inc., said in 1988 in a sworn affidavit filed in a lawsuit in Hawaii. Los Angeles-based Alpha, one of the largest manufacturers in the United States, is a wholly-owned subsidiary of Green Cross, a large Japanese drug company.

Documents show that, once introduced, the heat-treated concentrates came close to eliminating new cases of AIDS among American hemophiliacs. The National Hemophilia Foundation and the FDA have identified only 18 new infections since 1985 linked to heat-treated Factor VIII, FDA records obtained under the Freedom of Information Act show.

That compares with 1,044 hemophiliacs who had developed full-blown AIDS as of July 31 from Factor VIII made before heat-treated products became available. Because AIDS has a latency period of up to 10 years, that figure is expected to grow substantially as increasing numbers of infected hemophiliacs develop the disease.

"We really blew it on this," said Brownstein, executive director of the National Hemophilia Foundation, which was slow to encourage the use of heat- treated Factor VIII.

"We didn't have a consensus and we approached this from the view that we needed more definite scientific data. Then, when we saw later what it could do . . . it was stunning. We don't ever want to get burned like we did in 1983 again."

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Hemophiliacs have been both victims and beneficiaries of the plasma business.

Some are living longer, more productive lives as a result of new generations of Factor VIII concentrates. But AIDS has taken a heavy toll. And the cost of these new medicines now threatens to impoverish thousands of them. Some are beginning to run out of insurance coverage.

"This has placed an untenable burden on a group that has already been traumatized by AIDS. It has been devastating," said Dr. Louis M. Aledort, director of the hemophilia program at Mount Sinai Medical Center in New York City.

The price of Factor VIII last year increased between 600 percent and 900 percent after manufacturers switched from the heat-treated process to new technologies. Some manufacturers now use a mix of heat and detergents to kill viruses in the plasma, while others make a monoclonal version of Factor VIII - made by cloning the natural clotting proteins in plasma.

Hospital markups, added to the manufacturers' higher prices, have pushed costs even higher.

Last year, the Robert Wood Johnson Medical Center in New Brunswick, N. J., charged $1.50 a unit for concentrate it bought for 65 cents, according to FDA records. When a doctor complained, the medical center lowered the price to $1.15 a unit, the FDA records show.

A hemophiliac suffering from the severest form of the disease may use 50,000 or more units of Factor VIII a year, depending on how active he is. The annual price tag for the monoclonal version: $50,000 to $80,000.

By comparison, a patient with AIDS pays about $8,000 annually for AZT, a

drug that helps slow the virus' growth. Following months of protests and lobbying by advocates for AIDS victims, the company that makes AZT agreed recently to cut its price by 20 percent.

There have been no such price cutbacks for hemophiliacs. And Factor VIII remains one of the most expensive medicines ever marketed.

Manufacturers attribute their higher prices to the expense of developing the safer monoclonal product and to lower yields; the new process initially produced only about half as much clotting factor per liter of plasma as the old method, the manufacturers say.

"It's an entirely different process and it's just more expensive to make," Luchese of Armour Pharmaceutical said when asked about it last fall.

Though yields have improved substantially since then, prices remain high.

"If your yields improve, then economics say the price should come down. That hasn't happened," said Brownstein of the National Hemophilia Foundation.

Manufacturers say that's because they are still recovering research and development costs. The higher prices also reflect cost-shifting that commonly occurs in the volatile plasma business - making up the losses in one product by raising the price of another.

For example, when revenues from albumin - a plasma protein used to treat burn victims and surgery patients - fell sharply three years ago after Japan's government cut its purchases by 25 percent, manufacturers moved to make up for that by increasing their prices for Factor VIII. Albumin was their largest- selling product, totaling more than $200 million in the United States alone.

"I'm not going to deny that reallocation goes on - it's how the economics of this business works. Everything is tied to what we get from a liter of plasma," said Anita Bessler, vice president for marketing for Baxter-Hyland Inc., the plasma division of Baxter Healthcare Corp.

"For purchasers of Factor VIII, I don't know that they are going to see any great change in price," she said. "And part of the reason for that is you are seeing manufacturers trying to recapture those lost albumin

revenues. "

Some doctors who work with hemophiliacs say they believe the manufacturers took advantage of the Factor VIII shortage to reap windfall profits - or at least to recover their development costs as quickly as possible.

Mount Sinai's Aledort questioned the timing of the decisions by Armour and Baxter-Hyland Inc. to stop selling heat-treated Factor VIII more than three months before the companies started marketing their new products last year.

Spokesmen for Armour Pharmaceutical and Baxter-Hyland said they removed their heat-treated Factor VIII from the market because there was still a small, but real, possibility that AIDS might be transmitted through the product.

Spokesmen for both companies said they believed at the time that their inventories would be adequate to cover demand during the three-month gap before a new cloned version of Factor VIII was available.

"In hindsight, it could have (had an impact on the shortage) but it shouldn't have had," said Bessler of Baxter-Hyland. "There was a three-month lead time. . . . We anticipated the yield swings, and we thought there would be enough inventory. . . . But a number of other things were happening. "

Among them: An estimated 50 million vials of Factor VIII made by the Red Cross - about 8 percent of the total U. S. supply - were quarantined by the FDA for six months because of safety concerns.

Manufacturers say that, by producing a purer concentrate in which extraneous proteins are eliminated, they are reducing the risk of transmitting viruses, making the product safer.

"If we have a very safe concentrate - whatever safe turns out to be - and it is so scarce and expensive that it is not readily available, where are we? " Dr. Carol Kasper asked at the March meeting.

Industry officials don't dispute that the higher prices have put a heavy

financial burden on hemophiliacs. But they were under heavy pressure to make a safer product, they say.

"The same treaters who are complaining now about the cost are the ones who encouraged the industry to develop products that were viral-free, requiring substantial investments in new technology," said Reilly, president of the industry trade association.

"To the extent that we encouraged these companies to develop safer products, we are responsible," Brownstein acknowledged. "We are super- pleased with what appears to be a safe product. But we are very displeased with the financial consequences this has wrought. "

Last fall, as the Factor VIII shortage deepened, Luchese of Armour Pharmaceutical was asked about prices.

"Too often people make the mistake of saying we're gouging the public. And I can tell you nothing is further from the truth," Luchese said.

Five weeks later, Armour raised the price of its Factor VIII.

On Oct. 31, the company notified its customers that it was raising the price from 55 cents a unit to 65 cents, an increase of nearly 20 percent. The suggested list price for wholesale distributors and state and federal agencies was increased to 90 cents.

Jeff Richardson, a spokesman for Armour's parent corporation, Rorer Group Inc., said the increase was needed to pay for improvements at Armour's manufacturing plant in Kankakee, Ill., and to cover a $3 increase in fees paid to plasma donors - from $15 to $18.

According to the National Hemophilia Foundation, three organizations - Alpha Therapeutics Inc., Cutter Biologicals Inc. and the New York Blood Center - raised the prices of their older heat-treated Factor VIII following the introduction of the monoclonal products last year.

"The increases averaged from 52 percent to 122 percent and they all occurred after the newer products (were introduced)," Brownstein said. "I don't understand that. The costs of making these products didn't change. "

Spokesmen for Alpha declined to respond. The vast majority of Alpha's products are sold in Japan.

Spokesmen for the other two companies said the increased costs reflected higher plasma collection and manufacturing costs. They declined to provide more specific details, saying the information was proprietary.

Manufacturers who continued to ship substantial amounts of Factor VIII to Japan and European countries during the shortage were asked about that.

"We developed an allocation program during the shortage, both in the U. S. and countries outside the U. S.," said Bessler of Baxter-Hyland. She declined to disclose either the percentage or the amount of Factor VIII that Baxter- Hyland shipped overseas. In addition to the United States, Baxter-Hyland sells concentrate in Japan, Holland and Canada.

Cutter Biologicals also continued selling Factor VIII overseas during the shortage.

"We continue to supply all of the markets we sold in before, which is basically West Germany, Japan and the U. S.," said Sunil Bhonsle, director of plasma procurement for Cutter. "I know we've had to face shortages in all of these markets. So we've not supplied one and not the other. " He, too, declined to say what percentage of the company's Factor VIII is shipped overseas.

Luchese said Armour had sold "a small amount" of its new Factor VIII product in Europe. "But this is the truth: I could ship out five million units tomorrow to Europe, and I could get a significantly higher price. The reason we're not doing that is there is a tight supply in this country, and we're respecting that," Luchese said.

Brownstein said the National Hemophilia Foundation had difficulty monitoring how much Factor VIII was shipped out of the United States during the crisis. What data officials were able to gather indicated "we were being disproportionately burdened," he said. "We thought they were playing a shell game with us. "

Foundation officials attempted to "jawbone" manufacturers to increase U. S. supplies but without much success, Brownstein said.

"That's why we originally asked the government to step in, to create the specter of government involvement. We also touched base with several people in Congress and had them make inquiries," Brownstein said.

The industry's response?

"The companies came back and threatened us and said they don't have to stay in the market. They can drop it (making Factor VIII). It was kind of a classic threat," Brownstein said.

Government officials weren't much help, either. National Hemophilia Foundation representatives met with officials in the U. S. Department of Health and Human Services and appealed to them to take steps to protect hemophiliacs in the United States.

"We went to HHS, held several meetings, wrote letters, begging the government to either mandate no exportation or to grant the industry immunity for malpractice (so companies could sell potentially less safe Factor VIII without fear of being sued). They were all very sympathetic and nobody did a thing," said Aledort of Mount Sinai Medical Center in New York.

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When the shortage reached a critical level last fall, doctors in the United States stopped performing all but emergency surgery on hemophiliacs. And they

cut back the amount of Factor VIII given to hemophiliacs to administer to themselves at home.

That forced many hemophiliacs to curtail their lifestyles and increased their dependence on special treatment centers in hospitals. There are eight such centers in Pennsylvania and two in New Jersey.

The center at Thomas Jefferson University Hospital in Philadelphia had to temporarily suspend its home therapy program for hemophiliacs in June 1988, when supplies of Factor VIII reached low levels.

"We set aside enough to make sure we could cover any emergencies. But in June we realized we didn't have enough to continue home therapy," said Joan Tannenbaum, coordinator of the hemophilia center at Thomas Jefferson.

"Normally we would distribute two cases of Factor VIII at a time for patients on home care, enough to cover two months' worth of infusions. By May, we were down to distributing one month. By July, we were giving out two vials per patient, enough for two infusions," Tannenbaum said.

As a result, hemophiliacs had to cut back on activities that might put them in danger of injuries, forgo dental work and elective surgery and come into the center more frequently for treatment and supplies, she said.

At Orthopedic Hospital in Los Angeles, which has one of the largest programs for hemophiliacs in the country, Kasper made her decision at the height of the shortage.

She asked her adult patients to remain on the heat-treated Factor VIII so the children could get the limited supply of monoclonal clotting factor.

Most of the adults agreed with her decision to help the children.

"It was a very emotional time for us and a very painful thing to do," Kasper said.

The supply situation at Jefferson and Orthopedic Hospital has improved greatly in recent months. But prices are still high.

Said Brownstein: "If you've got the money you can get monoclonal products, but there's still a real shortage of less expensive alternatives."