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Concerns about a dwindling blood supply are driving many ICU physicians and researchers to simultaneously rethink their transfusion practices and consider new technologies.
The physician population needs to begin making the situation better by better understanding transfusion medicine and guidelines, says A. Gerson Greenburg, MD, PhD, surgeon in chief at Miriam Hospital in Providence, RI, who also is a professor of surgery at Brown University. "A lot of blood is given inappropriately, without an indication to use the product," Greenburg says. "There’s a lot of knee-jerk reaction that goes back to an out-of-context statement made in the 1940s about what constitutes a transfusion trigger."
Greenburg’s department participated in a transfusion trigger study that evaluated whether patients kept above 10 g/dL fared better than those kept at 8 g. "We found no differences in outcomes when we used 8 g as a trigger point," he says. "And we managed to save over 2 units of blood per patient, which is tremendous. Viewing a hemoglobin of 10 as a transfusion trigger no longer applies."
In the past, says David J. Pierson, MD, FACP, FCCP, many intensivists have used a hematocrit (Hct) threshold of about 30 for transfusion. Pierson, who is professor of medicine at the University of Washington and medical director of respiratory care at the Harborview Medical Center in Seattle, says recent studies found that patients who were allowed to be more anemic before transfusion actually did better.
"Everyone would agree that a patient with cardiac ischemia should be transfused at a higher Hct threshold than others, all things otherwise being equal," Pierson says. "It appears safe to say that we have used more red blood cell [RBC] transfusion in the past than we absolutely needed."
Harvey G. Klein, MD, says the correct hematocrit level is controversial now following a study of patients in Canada that showed a lower hematocrit appears to be better than a higher hematocrit,1 contrary to conventional wisdom. Canadian researchers studied 838 critically ill patients with euvolemia after initial treatment with hemoglobin concentrations of less than 9 g/dL within 72 hours after admission to the intensive care unit.
RBCs were transfused for 418 randomly assigned patients if the hemoglobin concentration dropped below 7 g/dL and hemoglobin concentrations were maintained at 7-9 g/dL. The remaining 420 patients received transfusions when the hemoglobin concentration fell below 10 g/dL and hemoglobin concentrations were maintained at 10-12 g/dL.
The research team found the 30-day mortality was similar between the 2 groups (18.7% vs 23.3%; P = 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill.2
Klein, who heads the department of transfusion medicine at the Warren G. Magnuson Clinical Center of the National Institutes of Health (NIH) in Bethesda, Md, is also president of the American Association of Blood Banks. He says the study is also in line with common sense because the hematocrit wasn’t extremely low.
"The current belief is that the hematocrit should range between 8-10 but doesn’t necessarily have to be brought back up to normal," Klein says. "Raising the Hct to levels we might consider normal may in fact have a deleterious effect, though that probably needs to be confirmed."
Pierson agrees, observing that a physician who previously transfused patients without severe cardiac disease, acute brain disease, or uncorrectable hypoxemia whenever the Hct dipped below 30%, could probably lower that threshold to the mid-20s without causing worse patient outcomes. "I see lower transfusion thresholds being used in the ICUs in which I work than was the case 2-3 years ago," he says.
Use the Options at Hand and Watch the Horizon
Reassessing the Hct levels at which patients need to be transfused goes hand-in-glove with carefully husbanding a decreasing blood supply and more effectively using the options already available, Greenburg observes. "We can’t easily salvage ICU patients’ blood, but we can increase blood reserves through the operating room by using products that allow autologus transfusion," he says. "And if we practice surgery as if every patient is a Jehovah’s Witness, we don’t need to use a lot of blood, and Jehovah’s Witnesses don’t have a higher surgical death rate."
However, Greenburg is quick to say that while minimizing blood loss can preserve the blood supply, the tradeoff is longer operations and different techniques. "The kind of bleeding that creates a need for transfusion has to be operated on, clamped, or sewn. The micro bleeding associated with much of surgery isn’t really a problem," he says.
New products are on the horizon that may redirect some of the more than $15 billion spent annually worldwide to acquire RBC units. One such option is Hemolink, a human hemoglobin-based oxygen carrier that Greenburg says will be very useful if approved by the Food and Drug Administration (FDA).
The product would temporarily replace the patient’s own withdrawn blood, which would later be transfused back. Hemolink has completed phase III clinical trials in Canada and Europe and is currently involved in US phase III clinical trials for patients undergoing coronary artery bypass graft surgery.
Third-phase clinical trials for RBC substitutes show a statistically significant decrease in banked blood use for orthopedic and cardiac surgery, which would increase the overall banked blood supply.
Recombinant erythropoietin, which causes the body to make more RBCs, may well have a similar effect on RBC demand. Miriam Hospital is part of a major collaborative blind study to test the theory that giving erythropoietin in the ICU may reduce the need for blood transfusions, Greenburg says.
"The companies manufacturing the erythropoietin preparations would have us giving it to everyone, but these agents are expensive," Pierson says. "It takes many days for them to act, their proper role has not been defined, and the data aren’t in as to who should receive them."
Erythropoeitin has its place, Klein adds, especially for patients with renal disease. "But it really has limited use in the ICU," he says.
Safety and Availability Hot Issues
Klein says one positive technological is the degree to which labeling both the unit of blood and the patient has improved. "Before current technology, labeling was done manually, but the risk of giving an inappropriate unit of blood ranged from one in 19,000 to one in 12,000 units transfused," he says. "Compare that with the HIV risk of one in every million-and-a-half units transfused and you can see that labeling and identification technology, now generally computerized, has dramatically decreased the risk of giving the wrong blood."
Klein observes that most errors, whether in the ICU or operating room, occur during sudden emergencies when failsafe systems are bypassed.
"Call that a human factor, standard operating procedure, error control, whatever," he says. "It’s extremely important, whether it’s high tech, medium tech, low tech, or no tech."
Jerry Squires, MD, vice president and chief scientific officer for the Red Cross, says that his organization has invested $335 million in blood safety initiatives. "I think by and large, blood centers are making every effort to make the blood supply as safe as it can be," Squires says.
Squires says that current media attention to the variant of Creutzfeldt-Jakob disease (vCJD) popularly referred to as "mad cow disease" highlights mounting public fears about blood supply safety. The Red Cross is now indefinitely deferring donations from people who have spent 3 months in the United Kingdom or in Western Europe for 6 months or if they have received a blood transfusion in the United Kingdom. Current FDA deferral is 6 months for UK visitors, with suggested guidance of 5 years deferral for people who have lived in Western Europe.
According to Squires, the Red Cross tightened donation deferral because of documented vCJD cases in animals in other European countries. "There is no documented case of vCJD transmission to a patient through transfusion, but the disease can have a latency period as long as 20 years," he says.
Greenburg believes public concern about blood safety is also driving the medical community to find alternatives. "I have lots of patients who look at the informed consent and scratch off the blood transfusion piece," he says. "There is a perception (with data on both sides) that blood transfusions cause immune suppression."
Squires says his organization led a nationwide effort to implement nucleic acid testing, which has the potential to lessen the already-low risk of receiving HIV or hepatitis C through a blood transfusion. "It used to be that the window period between infection and when a donor actually tested positive was up to 90 days," Squires says. "With nucleic acid testing, that’s reduced to 30 days." Klein adds that most institutions will go 10-20 years without seeing a transfusion-transmitted HIV infection. "It will never be perfect, but the US blood supply is extremely safe," he says.
Using leukocyte-free RBCs has decreased the incidence of minor transfusion reactions and incidence of infection with cytomegalovirus (CMV). "Those of us with normal immune systems don’t have much trouble with CMV," Squires says. "I’m CMV-positive and I don’t even know when I was infected. However, premature neonates and immunocompromised patients are very seriously affected by CMV."
Squires points out that this year, the Red Cross has increased blood collections by 1.9%. At the same time, blood distributions to hospitals have increased 4.1%. To increase blood donations, the Red Cross is mounting an ad campaign on radio and TV and sending out millions of request letters to donors of record.
Greenburg says the press and TV news inadvertently contribute to the donor apathy responsible for current low blood reserves. "The evening news reports that a product has been approved for transfusion in another part of the world," Greenburg says. "There is a public perception that other things are available but that’s not really true."
Tracking TRALI in the ICU
According to Klein, the noninfectious serious hazards of transfusion are greatly underappreciated. ICU physicians may confuse transfusion related acute lung injury (TRALI) with fluid overload or with various acute respirator syndromes. "TRALI is a very specific disorder related to blood transfusions or to transfusion of antibody-containing plasma," Klein says. "It causes an acute lung syndrome that looks like pulmonary edema. It’s an immune side effect that usually occurs during transfusion but can occur up to a couple of hours afterward." He advises ICU physicians to use oxygenation, careful monitoring, and stopping the plasma flow from that donor—not volume restriction—to treat TRALI.
"ICU physicians need to be aware that this is different from fluid overload," Klein says. "Once you appreciate that this acute lung syndrome is transfusion-related, the blood bank can help you."
Klein also observes physicians aren’t usually concerned about blood availability in the ICU. "When someone is dying, we don’t say We don’t have blood for you.’ We find it," he says.
But ICU physicians, says Klein, need to be cognizant of the fact that blood is short in the United States, and for a lot of reasons is likely to become less available than it is now.
"Family members and friends of intensive care patients frequently ask what they can do to help," he says. "Tell them they can give blood."
1. Hébert P, et al. N Engl J Med. 1999;340:409-417; 438-447.