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October 2000
Cover Story
Anne Paxton
It could be the single biggest health innovation in transfusion
medicine since the HIV and HCV tests. It could be a waste of hundreds
of millions of dollars much better spent on other blood safety measures.
But whether one sides with its proponents or its foes, universal
leukocyte reduction , or ULR, will soon have taken hold at half
of the nation’s blood centers-probably long before the controversy
over its merits dies down.
Leukocyte reduction as a blood safety precaution has been used
on select patients since the 1980s. But it was not until 1998 that
some blood organizations began pressing to have all blood products
subject to the leukocyte reduction filtering process.
Since then, the Food and Drug Administration has endorsed ULR-though
it hasn’t formally mandated it, many European countries have mandated
it, and the pressure to adopt it everywhere in the United States
has steadily intensified. "The big problem is the ’U’ that goes
in front of the ’LR,’" says Herbert Silver, MD, medical director
of transfusion medicine at Hartford Hospital, Hartford, Conn.
Last spring, the American Red Cross announced that all of its
service regions will be converted to ULR by the end of the year.
Blood centers affiliated with America’s Blood Centers, which represent
almost half of the blood suppliers, are making the call on the local
level to use or not to use leukoreduced blood. In September, Rhode
Island Blood Center, which is the only blood center in the state,
became the first to provide 100 percent leukoreduced products to
all the hospitals in the state. Overall, an estimated 40 percent
of the nation’s blood supply is already being leukoreduced.
But the added expense of roughly 20 to 25 percent per unit, or
much more by some estimates, makes opting for ULR a high-stakes
choice. "What we’re talking about here is a cost increase to the
health care system in the neighborhood of $300 million," says James
MacPherson, chief executive officer of America’s Blood Centers,
Washington, DC.
To date, the College has taken no position on ULR. But many specialists
in transfusion medicine fear that adoption of ULR means an important
clinical decision is being taken away from physicians and imposed
on them by blood centers. "I believe the decision whether or not
to provide a cellular component as leukocyte-reduced is the practice
of medicine," says James P. AuBuchon, MD, professor of pathology
and medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH. "Therefore
this choice should be made by physicians responsible for the patient’s
care."
On the other hand, Edward L. Snyder, MD, professor of laboratory
medicine, Yale University School of Medicine, and director of blood
transfusion services at Yale-New Haven Hospital in Connecticut,
argues that perhaps physicians need to look at the cost issue differently.
"Some physicians, in an attempt to control cost, resort to making
the point that there are not enough data" to establish the value
of ULR, he says. "There is no doubt it will cost money to universally
leukoreduce blood, but cost savings achieved in other areas would
make leukoreduction feasible. That is how we funded leukoreduction
at Yale."
The FDA’s position on ULR has done little to resolve these
opposing views. In September 1998 the FDA’s Blood Products Advisory
Committee was asked to decide whether the benefits of ULR outweigh
its risks. The committee voted "yes" 13-0, with three abstentions.
But the FDA announced June 16 of this year that it will not formally
recommend ULR in the guidance document it is preparing. Jay Epstein,
MD, director of the FDA’s Office of Blood Research and Review, said,
"FDA remains convinced at a scientific level independent of cost
that ULR is an improvement in safety and purity." But he stressed
the goal of expanding ULR on a voluntary level.
"Their legal advisors have told them they can’t mandate it, and they
can’t send out a guidance without changing the Code of Federal Regulations,
which is a very cumbersome and complex process and certainly can’t
be done quickly," says Lawrence Petz, MD, professor emeritus of pathology
and laboratory medicine at the University of California at Los Angeles.
"So I think there is no FDA mandate imminent-and there may never be
a mandate." A mandate may not be necessary, in fact, because if
ULR becomes clearly recognized as the industry standard, it will
influence the FDA’s licensure and review decisions and become a
de facto requirement. A December 1999 estimate by AdvaMed, the Advanced
Medical Technology Association (formerly the Health Industry Manufacturers
Association), predicted that with use of LR growing at six percent
per month, the United States will achieve ULR by December 2001.
In the meantime, the FDA is scrutinizing its quality control guidelines
for LR. Those guidelines call for QC testing of at least one percent
of products or a minimum of four per month, with 100 percent of
tested units containing <5.0 x 106 residual donor leukocytes per
final product. European guidelines are tighter: They define LR as
<1.0 x 106 residual leukocytes/unit and recommend sufficient testing
so as to detect a 10 percent failure rate in the LR process.
The FDA is considering the more stringent European specifications
as well as a stricter QC standard: a statistical approach to ensure
with 95 percent confidence at least 95 percent of the blood units
meet specifications, Jong-Hoon Lee, MD, said at a December 1999
workshop on ULR sponsored by the FDA. Dr. Lee is chief of the Blood
and Plasma Branch in the FDA’s Center for Biologics Evaluation and
Research.
Estimating the potential cost of ULR has become controversial
in itself. The American Association of Blood Banks says there are
three ways to come up with a figure. Based on the Canadian Coordinating
Office for Health Technology Assessment, ULR for the United States
can be estimated to cost $400 million per year. Based on figures
from the British government, ULR will cost the United States $672
million per year. And based on unit costs for 12 million red blood
cell units ($20 for leukocyte reduction plus $7 for labor, QC, and
overhead) and unit costs for 6 million platelet units ($40 for leukocyte
reduction plus $7 for labor, QC, and overhead), ULR would cost $606
million per year.
There is skepticism in some quarters about those numbers. "I think
some real questions need to be raised about the relationship of
added charges to leukoreduction to the true costs of doing it,"
says Laurence A. Sherman, MD, JD, chair of the CAP’s Transfusion-Transmitted
Viruses Committee and retired professor of pathology with Northwestern
University, Chicago. "The estimates I’ve heard and seen for the
costs of LR in the course of blood collection and processing are
significantly less than what I’ve seen and heard people are paying."
Whichever estimate is used, says Lawrence Goodnough, MD, professor
of medicine and pathology and immunology at Washington University
and director of the transfusion service at Barnes-Jewish Hospital,
St. Louis, he considers ULR a misallocation of money. He and 30
colleagues recently wrote a letter (Transfusion. 2000;40:751-752)
opposing implementation of ULR based on the scientific merits.
The FDA’s BPAC did agree that the benefit-to-risk ratio of LR
is sufficiently great to require ULR, he concedes. "However, the
minutes stated clearly many committee members agreed there are insufficient
studies and everyone wanted more data." But Dr. Goodnough also looks
askance at the origins of ULR. "As far as I’m concerned, this whole
controversy has nothing to do with blood safety. This is a business
plan implemented by the blood centers and commercial leukoreduction
companies."
To date, Dr. Goodnough adds, both LR and non-LR blood products remain
FDA-approved. After the BPAC vote, "all blood centers, not just the
Red Cross, had the clear understanding the FDA would give them two
years’ ramp-up time and eventually require ULR. Now it’s not going
to happen, so hospital-based transfusion medicine specialists like
me feel strongly this is the practice of medicine and needs to be
determined by a hospital transfusion committee." Hartford Hospital’s
Dr. Silver regards the FDA’s dodging of a formal rule as a softening
of its position that may take some of the pressure off blood centers
to move quickly toward adopting ULR. "I don’t see it as inevitable,"
he says. Dr. Petz concurs that ULR is the practice of medicine,
essentially taking what has been a clinical decision and denying
physicians the choice of non-leukoreduced products. "The question
is, who has responsibility for taking care of patients, and the
answer at hospitals is physicians," he says. "If a physician orders
a non-leukoreduced product for a patient, is it justifiable for
someone in the blood center to say we’ll send you leukoreduced products?"
According to the AABB, there is consensus that LR is appropriate
for three indications: prevention of febrile nonhemolytic reactions,
prevention of HLA alloimmunization, and prevention of transmission
of cytomegalovirus (Association Bulletin No. 99-7. Aug. 2, 1999).
These are the main reasons physicians order about 15 to 20 percent
of blood products leukoreduced now, and there is good evidence for
using LR cellular products for these patients, says Dr. Sherman.
Not conclusively substantiated by clinical trials, the AABB says,
are potential benefits including prevention of immunomodulation,
prevention of virus transmission other than CMV, and prevention
of transmission of variant Creutzfeldt-Jakob disease. There has
been clinical evidence both supporting and discrediting an association
between leukocyte reduction and a decreased risk of postoperative
infection, AABB reports. Age, type of surgery, previous open-heart
surgery, and preoperative platelet count are each more significant
predictors of postoperative mortality, the AABB says. The possibility
of transmission of some viruses less pathogenic than HTLV-I/II could
be decreased by LR, but the risk from these viruses is not considered
high. The consensus on vCJD is that LR is not likely to have any
significant impact on the transmission rate.
"Where there have been some data suggesting LR may decrease or
stop infection rates and the like, the evidence is not nearly as
clear-cut, and there may be confounding factors," Dr. Sherman maintains.
"Because the large bulk of patients fall into these other categories,
ULR becomes of questionable value in their case."
Neil Blumberg, MD, professor of pathology and laboratory medicine
and director of transfusion medicine for the blood bank at the University
of Rochester Medical Center, New York, views the evidence for transfusion
immunomodulation as convincing. "Of 10 randomized clinical trials,
eight support the position that transfusion immunomodulation is
clinically important," he says. (In contrast, only one study, he
says, demonstrates LR’s ability to prevent CMV transmission.) He
will present a paper at the AABB meeting next month describing an
implementation trial of LR transfusions in cardiac surgery. Bearing
out previous randomized trials, he reports, mean outcomes in transfused
surgical patients after LR was introduced improved for eight out
of eight clinical and economic variables, including deaths, ICU
hours, ventilator hours, antibiotic days, fever days, lengths of
stay, charges, and costs.
In this study, Dr. Blumberg and his colleagues found a net estimated
actual cost savings per year of $1,700 per patient after introduction
of leukoreduction. With half of the blood in the United States used
for surgery, he estimates nationwide savings of ULR could be as
high as $6 to $12 billion per year. "We didn’t include savings in
other types of patients, such as a reduced need for CMV serotesting,"
he adds. "We assumed the savings on postoperative morbidity would
greatly outweigh CMV and febrile reactions savings."
Dr. Petz finds the claim that LR reduces postoperative infection
to be not very well documented, and Dr. AuBuchon, too, believes
the research so far is inadequate. "The prospective studies that
have been published to date are all from Europe, they all used blood
components slightly different from what we use in this country,
and they have come to opposing conclusions despite similar designs,"
Dr. AuBuchon says. He expects that a prospective, randomized study
recently closed at Massachusetts General Hospital in Boston will
provide data early in 2001 that will determine whether ULR truly
decreases length of stay.
Even more controversial is the possible connection between transfusions
and immunomodulation over the long term. "These are questions that
have been percolating in everyone’s mind," says Ronald A. Sacher,
MD, new director of Hoxworth Blood Center at the University of Cincinnati
and previously professor of medicine, pathology, and oncology at
Georgetown University Medical Center, Washington, DC. "Why there
may be certain long-term immunological effects, what is the long-term
morbidity of the patients, what is the relationship of leukocyte
reduction in that equation. Perhaps long-lived leukocytes can produce
microchimerism, and this may play a role in potential immunosuppressive
effects of transfusion. The jury is still out on that."
Dr. Snyder, on the other hand, finds the evidence compelling and compares
leukoreduction to a tetanus shot. "I think to deny a young male or
female patient leukoreduced blood because there is no indication now
is to mortgage their future. If such a patient became ill in their
70s, they could present for cancer treatment already alloimmunized
because of a transfusion they got when younger. It’s similar, in my
perspective, to not giving a person a tetanus shot now because they’re
not likely to run into a rusty nail." Can leukocyte reduction
decrease the recurrence of cancer? Dr. Blumberg believes there is
strong evidence suggesting it does. "If as little as 10 percent
of the association between transfusion and increased death due to
cancer is causal (an increase in cancer death of one percent out
of a total nine percent observed difference), the mortality from
immunomodulation-induced cancer recurrence is estimated at 2,000
deaths per year."
"There are lots and lots of papers on this topic. It’s quite confusing,"
says Dr. Snyder. "Some show there are benefits of LR in preventing
tumor recurrence. Others show there are not. Then we have meta-analyses
which say maybe, and that’s my final answer."
On the issue of LR and graft-versus-host disease, he is more definite.
"There is a high level of consensus that LR will not prevent post-transfusion
graft-versus-host disease," Dr. Snyder said at the FDA workshop.
He maintains that gamma radiation is the most prudent measure. LR
will, however, probably enhance the safety of blood against bacteria,
he added. "But, due to various issues, suffice it to say that removal
of bacteria from blood by leukoreduction filters is not an indication
which will likely be translated into label copy."
Although adverse reactions to LR blood are rare, critics
of ULR suggest that more reactions could result if ULR is adopted.
Leukocyte reduction may be done in a blood center shortly after
the blood is collected (prestorage LR), at the hospital after the
blood has been delivered (in-lab post-storage LR), or near the patient
(bedside LR). Under current AABB standards, a leukocyte-reduced
component is defined as one with <5 x 106 residual donor leukocytes
per final product.
"There are different technologies involved in producing blood
components that are nearly devoid of white cell content," and sometimes
the technology affects the final component to induce either allergic
or idiosyncratic type reactions in transfusion recipients including
facial flushing and dyspnea, says Ira A. Shulman, MD, chair of CAP’s
Transfusion Medicine Resource Committee and vice chairman of the
Department of Pathology, LA County-USC Medical Center, Los Angeles.
Furthermore, depending on the filter set used and the storage duration
of red blood cells prior to filtration, hemolysis of red blood cells
may occur.
In fact, many of the drawbacks seen in leukoreduction have been
blamed on bedside filters. In May 1999 the FDA issued a medical
alert that bedside LR has been associated with serious hypotension;
other problems include complexity of the setup for a busy nursing
staff, inappropriate priming of the filters, filter clogging, and
return and discard of the blood product because of excessive time
outside adequate storage conditions. A formal study commissioned
by the Canadian government in 1998 found that prestorage leukocyte
reduction of platelets either by filtration or apheresis techniques
was an estimated four to five times more effective in preventing
febrile reactions than filtration after storage in the laboratory
or filtration at the bedside. Similarly, prestorage filtration of
red blood cells was 15 to 25 percent more efficacious than hospital
or bedside filtration.
The American Red Cross is performing a study, in collaboration
with the Army, on three different filters to determine which works
best. But Dr. Snyder believes a move away from bedside filtration
is desirable. "I think if we’re going to get the maximum benefit
of leukoreduction, it has to be prestorage," he said at the FDA
workshop.
Joseph D. Sweeney, MD, medical director of three hospital blood
banks and associate professor of medicine at Brown University, Providence,
RI, says transfusion medicine physicians are clearly correct in
stating the evidence for ULR is not conclusive, based on currently
published literature. "But if we look at many interventions in medicine,
we really don’t find they have been introduced after such trials,"
he points out. He cites magnetic resonance imaging as an example.
"An MRI costs twice as much as a CT scan. It gives better images
than a conventional CT scan, and it would be reasonable to conclude
that surgeons using MRI images might have better outcomes. But in
fact I don’t know of any randomized study that shows this."
"Similarly, with nucleic acid testing for HIV-1, we can’t prove at
this point it will make a material difference. Yet I don’t hear the
same opposition," he says. He attributes this in part to transfusion
medicine physicians having been slighted to some extent, because they
haven’t been consulted about their opinions, and leukoreduction is
an area that has been under their control. "In other areas like [adding
the test for] HIV-1, it was never a clinical decision; it was all
done in blood centers." "We are all very concerned, because of
the various diseases, particularly HIV, in the past 15 years, that
we don’t miss something we should have jumped on," Dr. Sherman says.
"For example, we’ve instituted HTLV-I testing at a time when we
had very limited data about its relationship to disease and frequency
in the donor population, but the feeling was we didn’t know enough
to say it was not consequential, and it would seem to have a very
long incubation period, so it might be a very long time before we
had enough data."
ULR has a definite additional cost, Dr. AuBuchon notes:
a diminishing donor pool. Because African-American donors with sickle-cell
trait have blood that tends to clog the filters, it is likely they
would be deferred. "Only about 10 percent of donated units come
from African-Americans, and only 10 percent of them are carriers,
but moving to ULR will reduce the available blood supply by one
percent," he cautions. "That seems small, but when we’re losing
two percent because of geographic deferrals for vCJD [donors who
visited the United Kingdom for six months or more between 1980 and
1996] and anticipating a shortage of blood already, that may be
important. Furthermore, explaining why this loss is occurring specifically
to one minority population may be difficult, and may result in loss
of allegiance of this and other minorities to blood donation."
As for the more traditional costs, Riverview Hospital in Noblesville,
Ind., found the savings from ULR made up for the expense. The 156-bed
hospital has been 100 percent leukoreduced since 1988, using filters
at the patients’ bedside, and began buying all prestorage-leukoreduced
blood products from a blood center in 1997. Nancy Chance, MLT(ASCP)
RMT, blood bank coordinator, says the hospital has not had any adverse
reactions to leukoreduced blood products, even when it was using
bedside filters. On the contrary, she says, "pre-medication and
nursing time for febrile reactions has been minimized to almost
nil," and several studies at Riverview have linked ULR with significant
cost reductions because fewer postoperative transfused infections
develop.
A Value Analysis Team at Riverview scrutinizes every new product-from
bedpans to blood-before it’s used, and leukoreduction underwent
the team’s full analysis. "Every department that plays a part in
the patient’s recovery has a representative on that team," Chance
says, "and their job is to play the devil’s advocate." Leukoreduced
blood wouldn’t have made it in the door in the first place and the
practice could not be maintained without the data to support it,
she says.
But Celso Bianco, MD, vice president of medical affairs at New
York Blood Center and immediate past president of America’s Blood
Centers, says Chance’s experience is unusual. "[The hospitals] don’t
believe in us when we tell them that in-hospital times and admissions
and all that will be shortened and that their costs will go down,"
he said at the FDA workshop. "I think that they really resent that
they have not been part of this process. We have been evolving our
thinking toward leukoreduction. . . . We have not been able to bring
all those participants of the health care system to come with us."
Not surprisingly, since hospitals are expected to bear the brunt
of ULR’s cost, they have been unenthusiastic about it. Eyeing the
unreimbursed blood safety measures of the last two decades, many
argue they can only absorb so many cost blows before those blows
start to cripple patient care.
Dr. AuBuchon sees dollars being misdirected in the push for ULR.
"If we are going to spend more money to make the blood supply safer,
there are already several larger, well-documented risks that patients
face that the field is not currently addressing. We already know
that bacterial contamination and mistransfusions each cause the
death of about two dozen patients annually in the U.S. and have
for decades. Yet, for reasons I don’t understand, the field is not
focused on that. Instead, it continues to focus on stamping out
the last case of viral transmission and potential risks rather than
actual ones." Also promising candidates, Dr. Sacher says, are refining
donor questionnaires and truthful completion of the questionnaires,
perhaps with technological strategies to speed up the process.
However, says Dr. Sweeney, it seems the cost-effectiveness criteria
that are being applied to ULR are different from the criteria applied
to other blood safety measures. The FDA requirement imposed in August
1999 that donors resident in the UK be declined "resulted in substantial
donor loss, as many as three percent," Dr. Sweeney says. "There was
really no justification for that request, considerable expense was
incurred, we’ve lost some repeat donors, and there was almost no outcry
from the transfusion community." Practically speaking, he says,
the additional cost of ULR will relate to filtering red blood cells.
He cites several factors, however, that will directly or indirectly
reduce the net cost of ULR-for example, savings from much less HLA
alloimmunization, eliminating CMV testing, being able to move more
patients through clinics because bedside filters aren’t needed,
and lack of need for nursing procedures or in-service training on
bedside filtration.
At least some hospitals have taken advantage of these in their
conversion. When Vanderbilt University Medical Center, Nashville,
Tenn., moved to 100 percent prestorage leukoreduction in September
1998, two weeks before the favorable vote by BPAC, "We did it in
a cost-neutral way," reports Anne Thomas Neff, MD, director of Vanderbilt’s
transfusion service.
Vanderbilt already was transfusing a significant percentage of
leukoreduced red blood cells because of its transplant and oncology
emphases. The vast majority of its blood products, however, were
not leukoreduced. The major impetus for Vanderbilt to move to ULR
was a study trial published in December 1997 that found no significant
advantage to giving patients single-donor platelets compared with
random-donor platelets as long as the platelets are leukoreduced.
"Once technology has caught up so that random-donor platelets
are more and more like single-donor platelets, that begs the question
associated with increased cost," Dr. Neff says. When the hospital
turned to the less expensive platelets product, "the money we saved
paid for the additional expense associated with red cells." Other
savings derived from not having to have two inventories of blood
products or keep filters in stock, and from using leukoreduction
as the equivalent of CMV-safe blood, she adds.
The question of how blood safety measures will be reimbursed,
of course, goes beyond ULR. MacPherson of America’s Blood Centers
points out there is a two- to three-year delay in adjustments to
Medicare and Medicaid payments under the DRG system, where most
transfusions take place. That means more trouble in the future,
he predicts. "Most of the new technology that’s coming down the
pike is going to be a whole lot more expensive. Technologies in
the future, like viral inactivation, are going to double or triple
the price of blood. So you can’t have a two- to three-year delay
when you try to talk about that."
Melissa McMillan, associate director of public relations for America’s
Blood Centers, says blood centers support a formal FDA rule on ULR
rather than a standard-of-care approach, in part because of reimbursement.
"When it comes to getting reimbursed by the Health Care Financing
Administration, having something just be standard of care is not
good enough." Since ULR is not included in the "market basket" used
to calculate hospitals’ DRG rates under prospective payment, blood
centers have been intensively lobbying Congress to adequately reimburse
hospitals for blood products.
Last December, when the Balanced Budget Refinement Act of 1999
was passed, the ABC, the American Association of Blood Banks, and
the American Red Cross were successful in getting specified outpatient
payment classifications (APCs) to cover blood, with reimbursement
amounts pegged to cost data provided by the blood groups. The inpatient
setting is not yet taken care of and still requires congressional
action. But now, said the FDA’s Dr. Epstein at the December workshop,
since HCFA has created a fee schedule for outpatient reimbursement,
"it is at least possible for blood centers to argue to hospitals
that the real cost of providing an inpatient unit is not less."
Inadequate reimbursement has become even more pressing in the last
year, McMillan adds, because up to now there have been small changes
in the cost of blood. For that reason, blood centers are also seeking
a long-term solution: a system that would set aside money to pay for
any new screening procedures blood suppliers must adopt.
Many supporters of ULR concur with opponents that without mad-cow
disease (transmissible spongiform encephalopathy) and the human
version, variant Creutzfeldt-Jakob Disease (vCJD), the concept of
ULR would never have reached critical mass. There has been no known
human case of vCJD contracted via blood transmission. ("And I imagine
if there were a human case the Internet would go ablaze," Dr. Shulman
says.) However, a recent Lancet article on transmission of TSE by
transfusion in sheep (Lancet. 2000;356:999-1000) has triggered a
flurry of discussion. As there is no evidence that leukocyte reduction
would prevent prion transmission in any case, even the Lancet article
is not compelling for ULR to prevent prion transmission.
Nevertheless, many western European nations, including Great Britain,
Austria, Germany, France, Portugal, Switzerland, and Ireland, have
imposed ULR because of vCJD. Canada, too, imposed ULR, and a large
factor there, Dr. Silver says, was a rash of hepatitis cases, blamed
on the government. "Canada was stung when they didn’t get in early
enough on hepatitis. As a result they’re gun-shy, so they’re going
in much more quickly" on new blood safety measures, he says.
Although there were scientific concerns, the political force spurring
the field has been concern about transmission of vCJD. "And I think
most people probably would agree that transmission of vCJD is unaffected
by leukoreduction," says Dr. Snyder.
"Nothing much would be happening now except for one thing, which
is that new variant CJD in Europe may be transmissible by transfusion,"
Dr. Blumberg contends. "We don’t think it’s likely, but we can’t
prove that, and there was some data that unlike CJD, the infectious
protein particle, the prion, was present in lymphocytes, so somebody
got the idea leukocyte reduction could reduce the risk. I don’t
know even if the FDA would have had the BPAC look at this issue
but for Europe. So the irony is we’re doing ULR not largely because
of research showing it’s beneficial, but because of a will o’ the
wisp concern to make up for the fact we didn’t stop the AIDS epidemic."
But whatever the motivations were that brought ULR to the BPAC’s
attention, Dr. Blumberg adds, "the decision to go with ULR is the
right public health decision."
Dr. Petz would like to see the United States make a decision on
ULR not influenced by the Europeans’ policies. "It’s true other
countries are doing it, but we in the United States should look
at the data ourselves and be a leader" on blood safety issues, he
says.
Transfusion experts tend to agree that if leukocyte reduction
did not add cost, fair-minded physicians would support it. "If it
was free, we’d all do it," is one blood expert’s assessment, because
few disagree that taking impurities out-and white cells are an impurity-is
a good thing. "If you asked me which type of blood transfusion I
want, I’d say leukoreduced, because of all these theoretical benefits,"
Dr. Sacher admits. "My personal view is that ULR may have significant
benefits because of immunomodulatory effects and prevention of long-term
morbidity. But that’s not proven, and whether in fact because of
theoretical benefits the country can support ULR at $500 million-that’s
the issue," he says.
David Pittman, MD, representing Barnes-Jewish Christian group in St.
Louis, pointed out at the FDA ULR workshop that the fixed reimbursement
hospitals receive means adopting ULR will force tradeoffs and could
compromise other hospital services. "What are we going to give up?
Are we going to have fewer nurses? Are we going to have less SOPs,
less adequate QC, fewer OR techs, fewer custodians? Because in our
system what gets cut in general is personnel, the people that actually
take care of the patients." Harvey G. Klein, MD, chief of the National
Institutes of Health’s Division of Transfusion Medicine Clinical Center,
agrees. "The FDA’s own mandate is safety and efficacy, not cost, but
cost may be a safety factor if inappropriate expenditures prevent
more appropriate public health interventions." Many say if they
had the choice, ULR would not be their first priority, because more
solid data exists on other measures that would have an equal, if
not greater, impact on patient safety. Dr. Shulman cites, for example,
virally inactivated plasma products versus raw plasma, and plateletpheresis
transfusion versus pools of random platelets as "two issues which
are equally as important to transfusion practice but, for whatever
reason, are not being debated at this fever pitch."
Having been buffeted by various blood crises for the last two
decades, blood centers are at the center of a war between science
and emotion, mixed with politics. As a result, rejecting any promising
blood safety measure, even before all the evidence is in, can be
risky. But the risks include any adverse impact on health care,
says the FDA’s Dr. Lee: "You might produce the highest quality blood,
but if it results in lower quality patient care overall, then you
have defeated your public health mission."
As a matter of public policy, many experts say, the government
and third-party payers must decide how far they are willing to go
toward funding a mandate for 100 percent safety, especially as new
technologies emerge for removing subsets of cells from blood products
and sterilizing blood components of infection. "We have a kind of
’zero-sum’ game in health care" in which wins in one sector are
made at the expense of other sectors, Dr. Sherman says. "From an
ethical standpoint, we have to recognize that if we get more support
or resources for things we think are significant in the blood arena,
then it has the probability of reducing expenditures somewhere else."
Dr. Petz does not believe the payoff justifies adopting ULR. "If
someone gave me half a billion dollars and I spent it taking white
cells out, and they came back a year later and asked how many lives
have you saved, I’d have to answer not very many, if any at all."
Dr. Snyder, on the other hand, sees ULR as valuable and inevitable.
"My belief," he says, "is that non-leukoreduced blood products eventually
will go the way of fresh whole blood."
When the Consortium of University Health Centers meets in October
to discuss ULR, it will do what the FDA’s Blood Products Advisory
Committee was barred from doing when it voted on ULR in 1998: consider
the cost as well as the benefits. "When a new technology is absolutely
proven to be beneficial, it becomes compelling regardless of the
cost. But there still needs to be a way of recapturing the expenditure,"
says Dr. Shulman. "Otherwise we can be forced out of business-and
then we won’t be able to help anybody."
Anne Paxton is a freelance writer in Seattle.
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