ON THE TRAIL OF TAINTED BLOOD --
HEMOPHILIACS SAY U.S. COULD HAVE PREVENTED THEIR CONTRACTING AIDS
Donna Shaw, INQUIRER STAFF WRITER
Philadelphia Inquirer; FINAL Section:
EDITORIAL REVIEW & OPINION Page: E01
SUNDAY April 16, 1995
It is one of the little-known stories of World War II. Had
more attention been paid to it, hemophiliacs in the United States might
not be dying now at the rate of one a day.
It was 1944, five years into the war.
At Schick General Hospital in Clinton, Iowa, military
doctors were treating a steady stream of wounded men shipped home from
overseas. By year's end, Capt. Emanuel M. Rappaport of the U.S. Army
Medical Corps had detected a disturbing pattern.
Many of the soldiers were coming down with hepatitis, a
viral inflammation of the liver. The men had served in different parts
of the world but had one thing in common: Battlefield transfusions.
The plasma most received had been drawn from a number of
different pools, each made up of donations from dozens of people.
The implications soon were clear: Hepatitis was spreading
through plasma transfusions. And plasma pools could become tainted if
only one of the dozens of donors carried the virus.
In 1945, Rappaport went public with his findings, which by
then were apparent to many other doctors. His study, published in July
1945 in the Journal of the American Medical Association, concluded not
only that transfusions were to blame but that the "pooling of
plasma probably increases considerably the incidence of jaundice
(hepatitis) among the recipients."
In a larger study a year later, he proposed more stringent
screening of donors and urged immediate research on ways to kill viruses
in blood products.
"It is likely that this syndrome will be encountered .
. . more frequently in the future," he wrote.
Half a century later, that warning is at the heart of scores
of lawsuits involving the spread of another virus through blood. This
time, the patients are hemophiliacs, and the disease is AIDS.
A key issue in the litigation is why heat-treating
techniques that killed hepatitis - techniques first used by
Army-financed scientists back in the 1940s - were not perfected until
1983 for blood-clotting products used by hemophiliacs. By 1983, most of
the nation's hemophiliacs had contracted the AIDS virus through
blood-clotting medicine made from pooled human plasma.
An estimated 8,000 to 10,000 U.S. hemophiliacs were infected
with HIV, the AIDS virus, in the late 1970s and early 1980s. Also
infected were thousands of hemophiliacs in Canada, Europe, Japan and
elsewhere who used American products - as well as some wives,
girlfriends and newborns, who contracted HIV from them. (Hemophilia,
caused by too few clotting proteins in the blood, primarily affects
men.)
Today, hemophiliacs and their loved ones are demanding to
know why the federal government did not require sooner that
manufacturers purify the clotting products.
The manufacturers say they did all they could to make
hemophilia medicines safe, given what was known at the time. They also
say that until the early 1980s, they did not know how to kill viruses
without destroying plasma's blood-clotting proteins.
The history of how these decisions were made, and of how the
government failed to protect the lives of thousands of people
adequately, is of more than academic interest, because new viruses - and
newly discovered forms of existing ones, including HIV and hepatitis -
are appearing all the time. At stake could be the health not only of
hemophiliacs but of 40 million other people who receive plasma products
each year.
At a recent conference in Washington, blood experts from
around the world said it was only a matter of when - not if - the next
dangerous virus gets into the blood supply.
In early 1940, as it became apparent that the United States
might enter the war, the Army's medical department started planning for
a serious problem: shock resulting from battlefield blood loss.
Whole blood, the doctors feared, was too fragile to survive
the trip to faraway war zones. So in 1941 and 1942, military records
show, seven commercial laboratories were hired to freeze-dry plasma, the
yellowish, fluid portion of blood.
Among the labs were Cutter and Hyland, two of the four
manufacturers that are now defendants in the lawsuits filed by
hemophiliacs. Today, Cutter is a subsidiary of Miles Inc. of Pittsburgh,
while Hyland is part of Baxter Healthcare Corp. of Deerfield, Ill.
As the war raged and casualties mounted, so did hepatitis
cases.
World War II marked the first time that blood products were
used widely, and they helped save countless lives. But in Iowa, Capt.
Rappaport knew that other doctors, in the United States and in Europe,
were observing outbreaks similar to his. The medical literature included
several reports on what then was called homologous serum jaundice, or
what's now known as hepatitis B.
Rappaport's paper about his patients was published in 1945.
In a larger study a year later, he found that "hepatitis following
the use of pooled plasma occurred 14 times as frequently as after the
therapeutic use of whole blood."
Seventeen years after Rappaport published his study, his
conclusions were supported by the Army's Office of the Surgeon General,
which reported that "numerous" wartime cases of homologous
serum jaundice had resulted from transfusions. By late 1945,
"pooled plasma was indicted as the vehicle," reads the 1962
Army report.
The report goes a step further, concluding that the larger
the plasma pool, the more likely it was to contain hepatitis. During the
war, according to the report, each pool contained plasma from 50 or more
donors. And the pools grew progressively larger as the war went on.
"In retrospect, what happened was clear," the
report continues. "A single transfusion of blood is likely to cause
jaundice in only a small percentage of the recipients. When, however,
blood is pooled, as it is when plasma is processed, the chances of
contracting jaundice are correspondingly increased."
Attempts, many funded by the military, were made in the
1940s to kill hepatitis in whole plasma while retaining all its
therapeutic benefits. The studies were unsuccessful, according to
military records, because the ailment's cause was unknown and because no
laboratory animals were known to be susceptible to the virus.
Experiments with human volunteers from the military, prisons
and state hospitals were abandoned after it became clear that
plasma-induced hepatitis "carried a high risk of mortality"
and illness, one study said.
Once the conclusions drawn by Rappaport and other
researchers became well known, plasma fell out of favor as a substitute
for whole blood. By then, the war was winding down and doctors had an
alternative product: albumin, a plasma component.
Doctors knew that albumin, because it was heat-treated, was
unlikely to cause hepatitis. Heating at 140 degrees Fahrenheit for 10
hours killed the virus but did not kill albumin's therapeutic proteins.
Most scientists thought the same temperature would render plasma
worthless.
Interest in plasma was revived in 1950 when an Army-funded
team led by J. Garrott Allen, then of the University of Chicago,
reported that prolonged heating could kill hepatitis. Allen's method,
which called for heating liquid plasma at about 90 degrees Fahrenheit
for between three and six months, was reaffirmed in followup studies.
The method, though, also killed blood-clotting proteins.
Allen was not overly concerned about this because he was seeking
primarily to prove that liquid plasma was still useful as a substitute
for whole blood.
By the time Allen's study was published, the Korean War had
begun. Army doctors were treating the wounded with pooled plasma that
had been irradiated with ultraviolet light in an attempt to kill
hepatitis. It didn't work: Nearly 22 percent of the men who received
plasma contracted hepatitis.
In 1958, two more studies supported Allen.
Some blood banks began using his technique.
Many researchers took aim at hemophilia, an inherited
condition, usually passed from mothers to sons, in which there are few
or no clotting proteins in the blood. The scientists tried to separate
the proteins from plasma, with little success.
Then, in 1964, hemophilia treatment was revolutionized.
Stanford University scientist Judith Pool - who had studied under Allen
- and her colleagues developed cryoprecipitate, a human plasma residue
rich in clotting proteins. It came from a single donor or a few donors -
not from a plasma pool - and so was less likely to carry hepatitis or
other viruses.
For the first time, hemophiliacs could treat their disease
with injections at home instead of in a hospital.
Two years later came the next major stride: Baxter's Hyland
division further refined cryoprecipitate to make the world's first
freeze-dried blood-clotting concentrate. It was called Factor VIII,
after the most common clotting protein.
The products were made from increasingly larger plasma
pools, which made production more economical. While the Army had worried
about pools with up to 50 donors, the new clotting drugs were made from
pools with thousands - eventually tens of thousands - of donors.
Then came a 1968 study by Allan G. Redeker, a University of
Southern California physician who asserted that Allen's heating method
did not work so well after all. Experts called for renewed caution with
plasma.
The National Research Council, which had endorsed Allen's
heating technique, changed its mind, saying the Redeker study meant that
"serious doubt is cast on the safety of all pooled human-plasma
preparations."
The council said it saw few good reasons to use whole
plasma, especially since albumin was safer. Heat-treated plasma was
worthless for blood clotting since it was well known that heat killed
those proteins, the council noted.
Allen, who by then had moved on to Stanford, countered that
Redeker's work had contained serious flaws. And in an Army-financed
study published in 1969, Allen wrote that the National Research Council
had not done its homework.
He said Redeker had relied on plasma from two commercial
operations, Hyland and Courtland Laboratories, in Los Angeles. Those
labs, he said, used large pools of plasma from "skid row"
donors, who sold their blood for money. The pools, he said, were
therefore far more likely to carry disease and had to be heated longer.
What's more, Allen said, executives at the two labs admitted
to him that neither the council nor government regulators had made any
effort to inspect company records. Allen said there was evidence that
the labs had not adhered to his standards.
By the time Allen's rebuttal was published, the National
Institutes of Health had already approved the first freeze-dried
blood-clotting concentrates for sale.
They were not heated.
And they were made from pools containing the plasma of
thousands of donors, most of them paid.
In 1970, a study by researchers at the National Institutes
of Health, published in the Journal of the American Medical Association,
warned that just one unit of hepatitis-contaminated plasma could
contaminate an entire pool. Diluted 10 million times, it still was
infectious.
By the mid-1970s, most American hemophiliacs were taking the
new, easy-to-use concentrates, and government-funded
hemophilia-treatment centers had been established to offer comprehensive
care and training in use of the medicines. Life expectancy and life
quality for hemophiliacs had improved considerably.
It wasn't long, though, before hepatitis from blood products
had become a leading killer of hemophiliacs. But the government,
manufacturers of the blood-clotting concentrates, and some doctors
called this an acceptable risk, given the medicine's huge benefits, and
federal regulators allowed the medicines to be sold, with labels warning
about hepatitis.
The drug industry said it needed too much plasma to rely
solely on volunteer donors. No aggressive action was taken or demanded
by the government to kill hepatitis in blood products. The companies
were ordered to use the best available donor-screening tests for
hepatitis B, but the tests were not sensitive enough to detect the virus
every time. Some scientists, meanwhile, said the products were
dangerous.
In a 1974 letter to federal health officials, Judith Pool,
of Stanford, warned against a proposed national blood policy that
allowed the continued use of paid donors for hemophilia drugs. By then,
studies had found a strong association between paid donors and hepatitis
in recipients.
Paid donors were more likely to harbor viruses because so
many lived in poor areas that were breeding grounds for disease, the
studies said. The World Health Organization objected, in particular, to
what it called the exploitation of donors in Central and South America,
Asia and Africa, where numerous commercial plasma-collection centers had
been set up in the 1960s and '70s.
The proposed policy, Pool wrote, "in no way requires or
even encourages the use of volunteer blood . . . but assumes a
continuation of the dangerous, expensive, wasteful and unethical
purchase of plasma by pharmaceutical houses. . . ."
By 1975, the World Health Organization was advocating an
all-volunteer system of plasma donation. Federal regulators agreed with
the industry's argument that the
benefits outweighed the risks.
