Highlights of impact survey
The American Association of Blood Banks was ready to start
requiring its members to test platelets for bacterial contamination more
than 18 months ago. But there was a hitch in the process. Or there could
The AABB wasn’t breaking entirely new ground, because the CAP already
had a checklist question (TRM.44955) requiring a plan for bacterial detection
for laboratory accreditation in transfusion medicine. But the Food and
Drug Administration had consistently declined to impose a requirement
Then, at the last minute, officials at the Department of Health and Human
Services delivered a message to the AABB: Please hold off.
One week before the standard was due to take effect, HHS acting assistant
secretary of health Cristina V. Beato, MD, wrote to AABB president Kathleen
Sazama, MD, urging a delay in implementation. She cited "potentially
serious and possibly unintended effects on availability of platelet products"
and suggested waiting until a "clear plan" could be developed.
But Dr. Sazama responded that the AABB believed further delay would compromise
public safety and public health, and the AABB went ahead with its plan.
Though AABB Standard 126.96.36.199 adopted March 1, 2004, is voluntary, to be
accredited as a blood bank, you must meet AABB’s standard of platelet
And now there is both anecdotal and statistical evidence that, though
blood centers have had to adapt, and it hasn’t been easy for a few facilities,
the standard is making a difference in platelet safety—without the
severe shortages that some had feared.
Several hundred infections, and somewhere between 67 and 333 deaths annually,
are estimated to be caused by bacterial contamination of platelets in
the U.S., making it by far the greatest infectious risk of blood product
transfusion. Yet the federal government has no requirement that platelets,
transfused about 4 million times a year, be screened for bacteria.
Unlike red cell or whole blood components, which are stored at 1°
to 6°C, platelets must be maintained at 20° to 24°C to preserve
their function and survival. That storage temperature allows a broad range
of bacteria to multiply and potentially contaminate the unit.
For many years, blood experts have been concerned about the lack of regulation
of platelets. "Currently the FDA doesn’t speak to bacterial contamination
of platelets. You can be inspected by the FDA and do absolutely no testing
for bacteria, and the FDA inspector will not cite you," says James
P. AuBuchon, MD, chair of the CAP’s Transfusion Medicine Resource Committee
and medical director of the blood bank and transfusion service at Dartmouth
Hitchcock Medical Center, Lebanon, NH.
The FDA does regulate the instruments that can be used for bacterial
testing. The agency has cleared the BacT/Alert test manufactured by BioMérieux,
Durham, NC, an automated liquid culture system that measures increased
CO2 produced by bacterial proliferation, and the Pall eBDS Bacterial Detection
System made by Pall Medical, East Hills, NY, which measures changes in
oxygen concentration as an indicator of bacterial growth.
A third FDA-cleared method is the ScanSystem manufactured by Hemosystem,
a direct bacterial detection method based on fluorescent labeling followed
by laser scanning and computer analysis.
"But that is simply a clearance to put in a package insert that
the test can be used for that purpose," says Roslyn Yomtovian, MD,
director of the blood bank-transfusion medicine service at the University
Hospitals of Cleveland in Ohio. "So the only regulatory agencies
that have actually given direction about a requirement are AABB and the
CAP. The FDA hasn’t done this yet—but that’s not unusual."
As Dr. Beato’s letter confirmed, when the AABB imposed the standard,
"there was concern that there would be increased frequency of platelet
shortages," Dr. AuBuchon says. "Thankfully, that’s not occurred."
Surveys of blood centers since the AABB standard was adopted suggest
that for most of them, new shortages of platelets have not been an issue.
Last fall, the AABB sponsored an impact survey of its member institutions,
which was summarized before the HHS Advisory Committee on Blood Safety
and Availability in January. (Related article: Highlights
of impact survey.)
Three hundred fifty facilities, collectively responsible for collecting
43.3 percent of the nation’s random platelets and 65.9 percent of the
nation’s apheresis platelets, responded to the survey from the blood centers’
Interorganizational Task Force on Bacterial Contamination of Platelets.
The majority (64 percent of hospitals, 68 percent of transfusion services,
and 91 percent of blood centers) reported that the standard had no impact
on their ability to provide platelets for transfusion, and about half
said there had been no changes in their platelet inventory. Two-thirds
indicated no increased platelet outdating, though a few cited substantial
outdating, and one reported a 39 percent outdate rate.
The survey, which has been submitted for publication, showed a moderate
shift to using apheresis platelets, though the task force cautioned that
it could not link this shift to the imposition of the AABB’s standard,
since "this appears to be a continuance of a pre-existing trend."
Also apparent was the nation’s transition to including bacterial detection
as a form of quality control for platelet components. For apheresis platelets,
well over 90 percent were tested by means of a culture technique while
only a small portion of whole blood platelet concentrates were tested
A few blood centers reported an abrupt shift away from whole blood platelets,
according to an earlier survey taken by America’s Blood Centers right
after the AABB standard took effect. Four ABC centers said they had stopped
making whole blood platelets because it was not feasible to them to implement
bacterial detection for them, while others reported decreases in whole
blood platelet production.
ABC chief policy officer G. Michael Fitzpatrick, PhD, told HHS that increased
time, staffing, and expense were among the effects blood centers cited
in that survey. "We added four staff to accommodate bacterial QC
in the production area," said one, while a few noted a substantial
increase in deliveries and purchases of additional incubators.
Changes in the timing of production were also noted: "We now release
apheresis platelets in two batches rather than one; one early afternoon
(used to be all) and one 7 to 9PM." And: "All WB platelets are
manufactured as early in the day as possible so that sampling can start
by 1PM the next day."
"Now that we’re screening platelets, the incidence of bacterial
infection is reduced," says Mark Brecher, MD, professor of pathology
and laboratory medicine at the University of North Carolina, Chapel Hill,
and director of transplantation and transfusion services in the Mc Lendon
Clinical Laboratories, "although the level of reduction has still
to be quantified."
However, preliminary data from the American Red Cross, presented at the
American Society for Microbiology meeting in June, show that since bacterial
testing began, "they’ve had three cases of post-transfusion platelet
sepsis, all with slow-growing organisms that were coagulase-negative staph,"
Dr. Brecher says.
"In the equivalent period of time before they began testing, they
had 12 reports. That suggests that potentially three-quarters of the cases
were prevented by the testing."
Dr. Yomtovian says she heartily endorses the standard and believes it
has significantly lowered the risk faced by people receiving platelets.
"Even looking retrospectively, I have no qualms about having put
the standard in effect, despite some of the other issues that have come
out as a result. If you’re the patient and you need platelets, the single-donor
platelets risk is much less than it was before," says Dr. Yomtovian,
who is professor of pathology at Case Western Reserve University School
She suggests that the risk of contamination in whole-blood-derived platelet
concentrates, also called random-donor platelets, is probably only marginally
lower than before the standard. "Random platelets also have to undergo
detection testing, but the methods used are much less sensitive in detecting
bacteria than the methods that are employed for apheresis."
This "duality of quality" continues to be the most burning
issue, in Dr. Yomtovian’s view. "One type of platelet is much safer
than the other, and there has to be something done to bring the safety
of platelets into equality."
For all types of detection testing, the blood components generally require
time for the organisms to proliferate before they can be detected. Cultures
conducted on the day of collection typically miss many bacterially contaminated
units that would become dangerous once the bacteria grew during storage.
As a result, platelets are held for 24 to 48 hours before tests are conducted.
"The downside of that is that every minute you add to the time you
hold the units at the front end, you’re losing time to give them on the
back end," Dr. Yomtovian says. "When you do bacterial testing,
you’re chopping days off use of the unit."
"Often before you even get a platelet unit in inventory in the blood
bank, it might already be in the third day of age. Previously it might
have been in the second or first day, but you’ll never have that anymore.
So you have much less time to move your inventory; therefore wastage has
At the same time, demand continues to rise. "It’s gone up every
year more or less for the last decade," Dr. Yomtovian says. "I
think it reflects an evolution in health care to more treatment for oncology
conditions, trauma, and transplants, and all of those require platelets,
"The standard hasn’t disrupted the system, but it’s certainly made
providing platelets more complicated," says Dr. AuBuchon. The difficulty
comes with platelet units derived from whole blood, which make up about
20 percent of all therapeutic doses of platelets transfused in the country.
"A few blood centers have taken up the charge and are culturing
these units. But it’s more expensive, because one has to culture each
unit individually. Rather than doing one culture per transfusion event
as is done for apheresis units, one has to perform five or six for all
the units that will be pooled together."
Since the units are only about 50 mL each, culturing each one individually
also significantly diminishes the total volume available for transfusion.
"Four or five mL out of a 300-mL unit is inconsequential, but four
to 10 out of a 50-mL unit from a whole blood unit is 10 percent of the
efficacy gone," Dr. Aubuchon says.
If the advice of manufacturers is followed and samples are obtained for
both anaerobic and aerobic cultures, Dr. Yomtovian points out, "you
could easily be using up to 15 mL of platelets—as much as a third
of the unit."
As a result, most whole-blood-derived platelets are not being cultured.
"The way most hospitals approach screening is by checking either
the pH in the unit or the glucose in the unit," Dr. AuBuchon says.
"One could check either one by automated methods like a pH meter
or glucose analytic device, but many chemistry services are using urine
dipsticks to measure these quantities."
"And if one combines the low inherent sensitivity with an analytic
method like dipsticks, which is only semiquantitative, there is certainly
the possibility of missing a truly contaminated unit," he adds. The
unit would have to have more than a million organisms per mL to turn the
Given these difficult testing logistics, and the multiplied risk of combining
several units, why use whole blood platelets at all?
Some patients do require apheresis, Dr. AuBuchon explains, but for patients
who are not immunocompromised, "whole blood is less expensive by
virtue of traditional pricing for hospitals, and it has a long track record
of being clinically efficacious, so many hospitals want to continue using
"We wouldn’t have enough platelets if we relied only on apheresis,
" Dr. Yomtovian says. "We have tried to increase our apheresis
platelets over time by producing them at our own donor center and purchasing
from outside sources, but there would still be a gap between supply and
"Some institutions continue to use pooled blood almost exclusively,"
Dr. Brecher says, "despite the fact that data suggest those units
are not as safe compared with single donor. The rationale is largely economic,
but, in addition, many experts feel it is wasteful to discard platelets
given in whole blood units."
Rhode Island, for example, has not followed the countrywide shift to
apheresis platelets. According to a report at the January meeting of the
HHS Advisory Committee on Blood Safety and Availability, 80 percent of
platelet transfusions in the state are whole-blood-derived.
But all platelets in Rhode Island are leukoreduced and cultured pre-storage,
so the bacterial contamination risks are equivalent to those of apheresis,
Joseph Sweeney, MD, director of coagulation and transfusion service at
The Miriam Hospital, Providence, told the advisory committee.
Pre-storage culturing is not the most common practice elsewhere in the
country. "No one in the field or the FDA is happy that we have two
tiers of safety with respect to platelet transfusions, with apheresis
units being tested effectively and whole blood for the most part not,"
Dr. AuBuchon says.
Pre-pooling of the random donor units, then culturing them, would solve
the problem of lost volume. "If the FDA would allow these random
platelets that come off of each whole blood donation to be mixed together
at the point of collection and stored like that, you would create a single
unit just like in apheresis, then testing could be done on the pooled
unit," Dr. Yomtovian says. "But that has not been cleared by
the FDA, so it can’t be done."
"Ironically, or paradoxically, one reason is if one unit is bacterially
contaminated and you mix it with four or five that are not contaminated,
you could actually get much more growth of the bacteria and it could be
"But it’s a circular argument," she adds, "because if
you have a method to detect bacteria, then you would eliminate those units
anyway. Many of us in the field have raised a question because pre-pooling
would certainly enable testing of random donor platelets virtually on
a par with single donor."
The FDA currently requires that transfusion occur within four hours of
pooling. "The rationale is that providing a larger volume into which
bacteria could grow would lead to a higher inoculant, leading to a more
severe event for the recipient," Dr. AuBuchon says.
"But that theory doesn’t have much scientific support. Bacteria
will top out at a particular concentration, probably on the order of 109
or 1012 /mL. The work we’ve done has indicated that’s not likely to happen,
that the maximum concentration is usually not reached in platelet storage."
In fact, Dr. Brecher says, many donors have antibodies against bacteria,
so pooling can bring self-sterilization of the unit, because "some
bacteria that were going to grow, now won’t."
New testing technology is showing promise of bringing greater speed and
efficiency to screening. For example, Verax Biomedical is developing a
lateral flow device, similar to a pregnancy test, to test for bacterial
contamination closer to the point of care.
"You would place a couple of drops of the platelet solution in the
center of a plastic cartridge, close it, and after 20 minutes read a result,
negative or positive, in a little window. It has a sensitivity of 1,000
organisms/mL," Dr. Brecher says.
Other companies are developing rapid, sensitive techniques to deal effectively
with whole-blood-derived units. "But we’re not there yet," Dr.
In reality, it’s difficult to judge the sensitivity of culturing methods
used now. "Obviously culturing is picking up something, because one
out of about every 5,000 has been confirmed to contain bacteria. But we
don’t know precisely what the sensitivity of this technique is because
we don’t know how many are being missed," Dr. AuBuchon says.
There has never been a controlled study of that issue. He says: "The
AABB bacterial contamination task force designed a protocol to prospectively
determine the sensitivity of culturing, but the cost was prohibitive.
It was estimated to cost from $8 to $10 million, so nobody stepped forward
to fund it."
But evidence is forthcoming. Users of the apheresis platelets made with
a cell separator manufactured by Gambro BCT Inc., Denver, in combination
with bacterial testing with aerobic and anaerobic culture using a BacT/Alert,
will be cleared for a storage extension to seven days, under an approach
the FDA approved in March. "Gambro has received approval for seven-day
storage of platelets collected in their apheresis system and cultured
according to a standard protocol," Dr. AuBuchon notes.
"Any units ultimately not transfused will get cultured after their
outdate, and that culture will essentially serve as the gold standard
to determine whether or not the unit was truly contaminated. Any blood
center wishing to use this approach must also agree to culture their outdated
Pall Medical has a similar application pending before the FDA for seven-day
storage of platelets using its eBDS system. The possible sticking point
for Pall is that the FDA wants detection of aerobic and anaerobic bacteria,
but Pall’s system does not detect strict anaerobes.
"If you look at the cases of bacterial sepsis over the last several
years due to platelet contamination, they have been predominantly aerobic,"
says Byron Selman, Pall Medical vice president of marketing. "We
have submitted to the FDA an alternate approach that would lead to enhanced
safety in blood, and we’ve been in discussions with the agency."
"This is a novel approach for the FDA," Dr. AuBuchon says.
"It’s not an agency known for taking chances, or for allowing a change
in established practice without data to document the sensitivity of a
technique being used. I congratulate them, and I agree that a seven-day
platelet that is cultured is superior to five years ago when we had a
five-day platelet not cultured."
In Europe, where platelets are manufactured a little differently, whole-blood-derived
platelets have been pooled for decades, and generally all cultured platelets
have a seven-day shelf-life. "Their rate of contamination is no more
or less than ours," Dr. Au Buchon says. While culturing is not universal
in Europe yet, it is commonly performed in blood centers there and, in
fact, "they prompted us to start culturing in 1999."
Richard C. Friedberg, MD, PhD, chairman of the Department of Pathology
at Baystate Medical Center, Springfield, Mass., expresses reservations
about the broad availability of long-shelf-life platelets. "Theoretically
seven-day platelets are wonderful. The big problem with five-day platelets
is always the three-day weekend, when Monday is a holiday so by Tuesday
you’re still trying to live off Friday’s platelets, and Wednesday the
same, because Tuesday’s platelets haven’t come out yet."
"But you’ve got to have automated systems at the speed you’d like,
and in a large-scale system you have to get the volume to the point where
it makes sense to do them.
"When we have a platelet collection system tightly associated with
an approved rapid method to confirm that the units are free of bacterial
contamination, then you can start talking about seven-day platelets that
While these issues are being worked out, laboratory accreditation programs
continue to strengthen their oversight of bacterial testing for platelets.
On the drawing board for the CAP’s Transfusion Medicine Resource Committee
is a proficiency-testing program. "We hope through PT that laboratories
will also begin to determine the sensitivity of these surrogate techniques
like glucose or pH," Dr. AuBuchon says.
"This PT system needs to be applicable to people who are culturing
platelets as well as those laboratories detecting bacteria through pH
or glucose testing," he says. "So it’s a bit of a challenge
to come up with a system applicable to two very different approaches."
But a pilot is underway, and they hope to be able to offer something
Anne Paxton is a writer in Seattle.