Published: Oct. 5, 2004
Updated: Nov. 3, 2004
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By Duke Medicine News and Communications
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.