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DURHAM, N.C. – Heart patients are more than twice as likely
to die during their first 30 days of hospitalization if they
receive a blood transfusion to treat blood loss or anemia,
according to a new analysis by cardiologists at the Duke
Clinical Research Institute (DCRI).

Additionally, such patients are more than three times as
likely to suffer a heart attack within 30 days, when compared
to those who did not receive a transfusion.

These findings -- which emerged after a retrospective
analysis of the treatments received by more than 24,000
patients hospitalized with an acute coronary syndrome -- run
counter to earlier and smaller observational studies. For this
reason, the researchers believe that a large randomized
clinical trial needs to be initiated to resolve the issue and
provide clear evidence-based guidance on how best to treat
these patients.

"Until such a trial can be conducted to resolve the
differences between our study and past studies, we suggest
caution in the routine use of blood transfusion for heart
patients who are stable," said Duke cardiologist Sunil Rao,
M.D., lead author of a study. For example, Rao said that
cardiologists should not automatically order blood transfusions
for anemic patients. The study results will be published Oct.
6, 2004, in the Journal of the American Medical Association.
"The risks of transfusion remained even after we statistically
controlled for other factors, such age, other illnesses and
timing of the transfusions."

This issue is an important one, the researchers said, since
cardiologists are now more aggressive in the treatment of
patients who come to the hospital with symptoms of a heart
attack. Physicians will often use clot-busting drugs or
angioplasty procedures in an attempt to quickly re-open clogged
arteries and save at-risk heart muscle. These treatments, as
well as the routine drawing of blood for laboratory tests
during hospitalization, can often leave patients with blood
loss or anemia, a condition marked by decreased levels of
oxygen-carrying red blood cells.

"Many physicians, upon learning that their heart patients
are anemic, will reflexively order a blood transfusion,
believing that the additional red blood cells will deliver more
oxygen to the heart and other tissues," Rao said. "However,
there is data to suggest that oxygenation of the tissues do not
necessarily increase as a result of blood transfusion."

The better understand the effects of transfusion on patient
outcomes, the research team pooled the medical data from three
large randomized clinical trials involving patients with acute
coronary symdromes. Of the combined 24,111 patients, 10 percent
(2,401) received at least one blood transfusion during the
first 30 days of their hospitalization. The researchers found
that in general, the patients receiving transfusions were older
and had more additional medical problems.

Since the original clinical trials were not specifically
designed to study the effect of transfusion, the researchers
used three different statistical approaches in analyzing any
associations between transfusions and adverse outcomes. All
came to the same conclusions.

Specifically, the researchers found that 8 percent of
transfused patients had died after 30 days, compared to 3.08
percent for those who did not receive a transfusion. Heart
attacks occurred in 25.16 percent of those receiving additional
blood, compared to 8.16 percent for those who did not.

"The results of our analysis suggest that physicians should
look at the whole patient, and not just the blood count number,
when considering whether or not to transfuse someone," Rao
said. "If patients appear to be fine, except for an abnormal
blood number, it is probably best to hold off on transfusion.
The body is constantly replenishing its blood supply, so in
these patients it may be best to follow them to see if they can
raise their blood counts on their own. If they don't, then the
physician should investigate potential underlying causes why
the patient's body isn't responding."

According to Rao, the causes underlying the increased
incidence of adverse events after transfusion are unclear.
Previous studies have shown that transfused blood increases
oxygen delivery only in the most severely anemic patients.
Also, nitric oxide is essential for delivery of oxygen from the
hemoglobin in red blood cells to tissues. However, according to
Rao, nitric oxide has a short half-life, so by the time stored
blood has been transfused, the essential nitric oxide may have
been depleted.

It is also possible, Rao continued, that the transfused
blood may stimulate an immune response that can exacerbate
already existing coronary artery disease.

"All of these factors, taken together, may act to promote
ischemia in the heart rather than mitigate it,' he said.

Rao's analysis was funded by the DCRI. The three trials from
which data was collected were GUSTO (Global Use of Strategies
to Open Occluded Coronary Arteries) IIb, PURSUIT (Platelet
Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression
Using Integrilin Therapy) and PARAGON (Platelet IIb/IIIa
Antagonism for the Reduction of Acute Coronary Syndrome Events
in a Global Organization Network) B.

Additional Duke members of the team were: James Jollis,
M.D., Robert Harrington, M.D., Christopher Granger, M.D.,
Kristin Newby, M.D., Lauren Linblad, Karen Piper, Jonathan
Stamler, M.D. (also a Howard Hughes Medical Institute
investigator) and Robert Califf, M.D. Other members of the team
were Eric Topol, M.D., Cleveland Clinic; Paul Armstrong, M.D.,
University of Alberta; and David Moliterno, M.D., University of
Kentucky.