Transfusion Medicine—Is Its Future Secure?

“Transfusion medicine will continue to be a little like walking through a tropical rainforest, where the known paths are clear but still require careful navigation, and new and unseen threats may still lurk around the next corner to trap the unwary.”—Ian M. Franklin, professor of transfusion medicine.

AFTER the worldwide AIDS epidemic cast the spotlight on blood in the 1980’s, efforts to eliminate its “unseen threats” intensified. Still, huge obstacles remain. 

In June 2005, the World Health Organization acknowledged: “The chance of receiving a safe transfusion . . . varies enormously from one country to another.” Why?
In many lands there are no nationally coordinated programs to ensure safety standards for the collection, testing, and transport of blood and blood products. Sometimes blood supplies are even stored dangerously—in poorly maintained domestic refrigerators and picnic boxes! Without safety standards in place, patients can be adversely affected by the blood drawn from someone who lives hundreds—if not thousands—of miles away.

Disease-Free Blood—A Moving Target

Some countries claim that their blood supply has never been safer. Yet, there are still reasons for caution. A “Circular of Information” prepared jointly by three U.S. blood agencies states on its first page: “WARNING: Because whole blood and blood components are made from human blood, they may carry a risk of transmitting infectious agents, eg, viruses. . . . Careful donor selection and available laboratory tests do not eliminate the hazard.”

 
Not without reason does Peter Carolan, the senior officer of the International Federation of Red Cross and Red Crescent Societies, say: “Absolute guarantees on blood supplies can never be given.” He adds: “There will always be new infections for which at that moment there is no test.”
What if a new infectious agent were to appear—one that, like AIDS, remains in an undetectable carrier state for a long time and is readily transmitted by means of blood? Speaking at a medical conference in Prague, Czech Republic, in April 2005, Dr. Harvey G. Klein of the U.S. National Institutes of Health called that prospect sobering. He added: “The blood component collectors would be scarcely better prepared to interdict a transfusion-transmitted epidemic than they were during the early days of AIDS.”

Mistakes and Transfusion Reactions

What are the greatest transfusion-related threats to patients in developed countries? Errors and immunologic reactions. Regarding a 2001 Canadian study, the Globe and Mail newspaper reported that thousands of blood transfusions involved near-misses because of “collecting blood samples from the wrong patient, mislabelling samples and requesting blood for the wrong patient.” Such mistakes cost the lives of at least 441 people in the United States between 1995 and 2001.
Those who receive blood from another person face risks essentially similar to those undergoing an organ transplant. Immune responses tend to reject foreign tissue. In some cases, blood transfusions can actually prevent the activation of natural immune responses. Such immunosuppression leaves the patient vulnerable to postoperative infections and to viruses that had previously been inactive. It is no wonder that Professor Ian M. Franklin, quoted at the outset of this article, encourages clinicians to “think once, twice and three times before transfusing patients.”

Experts Speak Out

Armed with such knowledge, a growing number of health-care workers are taking a more critical look at transfusion medicine. Reports the reference work Dailey’s Notes on Blood: “Some physicians maintain that allogeneic blood [blood from another human] is a dangerous drug and that its use would be banned if it were evaluated by the same standards as other drugs.”

 
Late in 2004, Professor Bruce Spiess said the following about transfusing a primary blood component into patients undergoing heart surgery: “There are few if any [medical] articles that support transfusion actually improving patient outcome.” In fact, he writes that many such transfusions “may do more harm than good in virtually every instance except trauma,” increasing “the risk of pneumonia, infections, heart attacks and strokes.”

 
It surprises many to learn that the standards for administering blood are not nearly as uniform as one would expect. Dr. Gabriel Pedraza recently reminded his colleagues in Chile that “transfusion is a poorly defined practice,” one that makes it “difficult to . . . apply universally accepted guidelines.” No wonder Brian McClelland, director of Edinburgh and Scotland Blood Transfusion Service, asks doctors to “remember that a transfusion is a transplant and therefore not a trivial decision.” He suggests that doctors ponder the question, “If this was myself or my child, would I agree to the transfusion?”
In truth, more than a few health-care workers express themselves as did one hematologist, who told Awake!: “We transfusion-medicine specialists do not like to get or to give blood.” If this is the feeling among some well-trained individuals in the medical community, how should patients feel?

Will Medicine Change?

‘If transfusion medicine is so fraught with dangers,’ you might wonder, ‘why is blood still used so extensively, particularly when there are alternatives?’ One reason is that many doctors are simply reluctant to change treatment methods or are unaware of therapies that are currently used as alternatives to transfusions. According to an article in the journal Transfusion, “physicians make transfusion decisions based upon their past teaching, enculturation, and ‘clinical judgment.’”
A surgeon’s skills also make a difference. Dr. Beverley Hunt, of London, England, writes that “blood loss is highly variable between surgeons, and there is increasing interest in training surgeons in adequate surgical haemostasis [methods to stop bleeding].” Others claim that the costs of transfusion alternatives are too high, although reports are emerging that prove otherwise. Many doctors, however, would agree with medical director Dr. Michael Rose, who says: “Any patient who receives bloodless medicine is, in essence, the recipient of the highest quality surgery that is possible.”

Death by TRALI

  Transfusion-related acute lung injury (TRALI), first reported in the early 1990’s, is a life-threatening immune reaction following a blood transfusion. It is now known that TRALI causes hundreds of deaths each year. Experts, however, suspect that the numbers are much higher, as many health-care workers do not recognize the symptoms. Although it is not clear what causes the reaction, according to the magazine New Scientist, the blood that causes it “appears to come primarily from people who have been exposed to a variety of blood groups in the past, such as . . . people who have had multiple transfusions.” One report states that TRALI is now near the top of the list for causes of transfusion-related deaths in the United States and Britain, making it “a bigger problem for blood banks than high-profile diseases like HIV.”

The Composition of Blood

  Blood donors generally give whole blood. In many cases, though, they donate plasma. While some countries transfuse whole blood, more commonly, blood is separated into its primary components before it is tested and used in transfusion medicine. Note the four primary components, their function, and the percentage of total blood volume each represents.
PLASMA constitutes between 52 and 62 percent of whole blood. It is a straw-colored fluid in which blood cells, proteins, and other substances are suspended and transported.
Water constitutes 91.5 percent of plasma. Proteins, from which plasma fractions are derived, constitute 7 percent of the plasma (including albumins, which make up about 4 percent of the plasma; globulins, about 3 percent; and fibrinogen, less than 1 percent). The remaining 1.5 percent of plasma is made up of other substances, such as nutrients, hormones, respiratory gases, electrolytes, vitamins, and nitrogenous wastes.
WHITE BLOOD CELLS (leukocytes) constitute less than 1 percent of whole blood. These attack and destroy potentially harmful foreign matter.
PLATELETS (thrombocytes) constitute less than 1 percent of whole blood. These form clots, blocking blood from exiting wounds.
RED BLOOD CELLS (erythrocytes) constitute between 38 and 48 percent of whole blood. These cells keep tissue alive by bringing oxygen to it and taking carbon dioxide away.
  Just as blood plasma can be a source of various fractions, other primary components can be processed to isolate smaller parts, or fractions. For example, hemoglobin is a fraction of the red blood cell.

A Physician Tells His Story

I WAS in the hospital auditorium, summarizing the results of an autopsy to a group of doctors. The patient who died had a malignant tumor, and I said, “We can conclude that the immediate cause of death in this patient was hemolysis [the destruction of red blood cells] and acute renal [kidney] failure caused by a massive blood transfusion.”
One professor stood up and angrily shouted, “Are you saying we transfused the wrong type of blood?” I answered, “That is not what I meant.” Showing some slides of tiny sections of the patient’s kidney, I added, “We can see lysis [disintegration] of multiple red blood cells in the kidney and can thus conclude that this caused acute kidney failure.”* The atmosphere grew tense, and my mouth went dry. Although I was a young doctor and he was a professor, I felt that I could not back down.
***
I chose to continue my studies in medicine by entering the field of pathology—the study of the characteristics, causes, and effects of disease.

While performing autopsies on patients who had died of cancer, I began to have my doubts regarding the efficacy of blood transfusions. Patients with advanced cancer may be anemic as a result of bleeding. Because chemotherapy exacerbates anemia, doctors often prescribe blood transfusions. However, I came to suspect that transfusions might simply cause the cancer to spread. At any rate, today it is known that blood transfusions cause immunosuppression, which can increase the possibility of tumor recurrence and decrease the survival rate of cancer patients.*

In 1975, I encountered the case mentioned at the outset. The professor had been in charge of the case and was a specialist in hematology. So it was no wonder that he was furious when he heard me say that a blood transfusion caused the patient’s death! However, I continued my presentation, and he gradually calmed down.

***
According to the textbook Modern Blood Banking and Transfusion Practices by Dr. Denise M. Harmening, “delayed hemolytic transfusion reaction” can occur “in a patient who has previously been sensitized by transfusion, pregnancy, or transplant.” In such cases, the antibodies that cause a patient to react adversely to a transfusion are “not detectable by standard pretransfusion methods.” 

According to Dailey’s Notes on Blood, hemolysis “can be triggered even when only a small amount of incompatible . . . blood is administered. When renal shutdown does occur the patient is slowly poisoned because the kidneys cannot remove impurities from the blood.”

 
The Journal of Clinical Oncology, August 1988, reported: “Patients receiving perioperative blood transfusions have a significantly worse prognosis than patients undergoing cancer surgery without a perioperative transfusion.”

The Growing Demand for Bloodless Medicine and Surgery

 

“All those dealing with blood and caring for surgical patients have to consider bloodless surgery.”—Dr. Joachim Boldt, professor of anesthesiology, Ludwigshafen, Germany.

“Blood transfusions are basically no good, and we are very aggressive in avoiding them for everybody,” says Dr. Alex Zapolanski, of San Francisco, California.

The general public too is becoming aware of the dangers of transfusions. Indeed, a 1996 poll revealed that 89 percent of Canadians would prefer an alternative to donated blood. “Not all patients will refuse homologous transfusions” states the Journal of Vascular Surgery. 

“Nonetheless, the risks of disease transmission and immunomodulation offer clear evidence that we must find alternatives for all of our patients.”