“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 kilometers 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, e.g, 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 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 the patient, mislabeling 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, “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 alternative 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 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 strawcolored fluid in which blood cells, proteins, and other substances are suspended and transported. Water constitutes 91.5 percent of plasma. Protein, 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.
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.
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 away.
FRACTIONATION: THE USE OF BLOOD’S LESSER INGREDIENTS IN MEDICINE
Science and technology make it possible to identify and extract elements from blood through process called FRACTIONATION. To illustrate: Seawater, which is 96.5 percent water, can be divided through fractionation processes in order to capture the remaining substances present, such as magnesium, bromine, and, of course, salt.
Likewise, blood plasma, which makes up more than half the volume of whole blood, is over 90 percent water and can be processed to harvest fractions including protein, such as albumin, fibrinogen, and various globulins.
As part of a treatment or therapy, a doctor might recommend concentrated amounts of a plasma fraction. An example of such is protein-rich cryoprecipitate, which is obtained by freezing and then thawing plasma.
This insoluble portion of plasma is rich in coagulation factors and is usually given to patients to stop bleeding. Other treatments may involve a product that contains a blood fraction, whether in trace amounts or as a primary ingredients.
Some plasma proteins are used in routine injections that can help to increase immunity after exposure to infectious agents. Nearly all blood fractions being used in medicine applications consist of the protein found in blood plasma.
According to Science News, “scientists have identified only several hundred of the estimated thousands of proteins typically coursing through a person’s bloodstream.” As understanding of blood grows in the future, new products derived from these proteins may emerge.
Without question, there is a measure of truth in that quote. Blood is essential to all human life. It is a precious resource. Are you convinced, though, that it is safe and wise for humans to share that fluid for medical purposes?
As we have learnt, worldwide safety standards are highly variables, and treatments with blood are riskier than many assume. Furthermore, physicians differ widely in their use of blood because of education, skills, and viewpoints.
Yet, many are increasingly cautious about transfusing blood. A significant and growing number of doctors are showing a preference for medical treatments that avoid the use of blood.
That brings us back to a question posed at the outset of the article. Just what is it that makes blood so valuable? If the medical use of blood is increasingly questionable, is there another purpose that blood fulfills?
WHAT ARE HEMOGLOBIN-BASED OXYGEN CARRIERS?
Within each red blood cell are some 300 million hemoglobin molecules. Hemoglobin represents about one third of the volume of a mature red cell. Each molecule contains the protein globin and a pigment called HEME –which includes an iron atom.
When a red blood cell passes through the lungs, oxygen molecules penetrate the cell and attach themselves to hemoglobin molecules. Seconds later, the oxygen is discharged into body tissue, sustaining the life of the cells.
Some manufacturers now process hemoglobin, releasing it from human or bovine red blood cells. The extracted hemoglobin is then filtered to remove impurities, chemically modified and purified, mixed with a solution, and packaged.
The end product –not yet approved for use in most countries –is called a HEMOGLOBIN-BASED OXYGEN CARRIER, or HBOC. Since the heme is responsible for the rich red color of blood, a unit of HBOC looks just like a unit of blood cells, the primary component from which it is taken.
Unlike red blood cells, which must be refrigerated and discarded after a few weeks, the HBOC can be stored at room temperature and used months later. And since the cell membrane with its unique antigens is gone, severe reactions due to mismatched blood types pose no threat.
However, compared with other blood fractions, the HBOC presents more challenges to conscience. Why? As long as the HBOC is derived from blood, there are two objections that may be raised. One, the HBOC carries out the key function of a primary component of blood, the red cells. Two, hemoglobin, from which the HBOC is derived, makes up a significant portion of that component. Regarding this and similar products, then, conscientious people face a very serious decision