All You Need Is Blood
By recycling their own blood during surgery, patients reduce the chance of transfusion errors as well as their reliance on a dwindling blood supply.
The operating room should have been buzzing with the sounds of technicians wheeling in carts and turning on equipment. Scalpels and scissors should have been carefully arranged on a sterile table. Electronic monitors should have been blinking.
Ordinarily, nurses and technicians would have been preparing the patient, who needed a critical liver transplant. But the room was still and silent, and the patient lay waiting, because the donated blood that was needed for transfusion during the procedure was not yet available.
The same scene has played out across the country at countless hospitals and medical centers, where health professionals are at the mercy of a blood supply that all too frequently drops perilously low.
Yet on that same day, USC surgeons were performing another scheduled liver transplant, this time a “bloodless surgery”—a tightly choreographed procedure that requires no blood from donors. Surgeons such as Nicolas Jabbour, M.D., associate director of liver transplantation at USC University Hospital, have championed such procedures; he and his colleagues have performed 26 adult bloodless liver transplants since 1999, most of which involved living donors.
“Bloodless surgery was originally designed to serve patients who refused blood transfusions for religious reasons, but we believe it will take on a wider role in the future, as more surgeons adopt these techniques,” says Jabbour, associate professor of surgery at the Keck School of Medicine of USC.
Randy Henderson, director of transfusion-free medicine at USC University Hospital, says the expertise surgeons have developed in bloodless surgery makes for better surgeries overall. “We are very pleased with the outcomes for patients undergoing transfusion-free surgeries. Through careful and thoughtful management, the surgeons have really elevated the quality of care,” he says.
Obviously, not all surgeries require blood transfusions. A general rule of thumb, explains Jabbour, is that any procedure resulting in patients losing about 20 percent or more of their blood usually entails providing a transfusion to make sure patients stay healthy and stable during surgery and recovery.
Nearly 5 million Americans every year receive blood transfusions, for reasons ranging from scheduled surgeries to trauma and from burns to hemophilia. Experts predict that demand for blood will rise higher over the coming years, as the population ages. Already, more than half of the 13 million units of blood transfused annually goes to patients over age 60, Jabbour says, and he expects their needs will grow. Many older patients are undergoing surgeries for heart problems, joint replacements and solid cancers because of improved operating room and medical technologies—a trend that will require having more blood on hand.
At the same time, the safety restrictions placed on donated blood make it harder to obtain blood from donors. Some potential donors are excluded from donating because of their risk of prior exposure to diseases. A long list of tests for transmissible diseases done on donated blood also restricts part of the blood supply.
More widespread adoption of the techniques involved in bloodless surgery can help lighten the load, Jabbour says.
“A lot of scientific papers and established blood bankers have been predicting a blood shortage in the future, but the shortage is happening faster than expected,” he says.
Already, with sharpening expertise in bloodless surgery at USC, he says, physicians are finding ways to reduce their dependence on donated blood. At USC, he says, “the usage of blood in cadaveric transplants has been steadily decreasing, despite the fact that more patients who are receiving transplants these days are sicker and would tend to need more blood.”
Choreographed care
Here is how transfusion-free surgery works:
First, physicians prepare the patient before surgery by administering drugs, such as erythropoietin, that pump up the number of red cells in the blood.
Next, at the beginning of the procedure, they transfer one to four units of blood from the patient into a special bag, but leave it connected to the patient through a tube. At the same time an intravenous fluid—a sort of suspension—is infused into the patient, keeping the volume of liquid in the arteries, veins and the rest of the vascular system steady while diluting the remaining mass of blood cells. Any blood lost during the surgery is salvaged and re-infused into the patient.
During the operation, surgeons use lasers or cauterization techniques to stem any unnecessary bleeding.
Highly trained anesthesiologists use anesthesia that lowers blood pressure during surgery—as well as special monitoring technology—to minimize bleeding. At the end of the surgery, the removed blood is re-infused into the patient. As the patient recovers, physicians remove blood for testing only when absolutely necessary.
Jabbour says that because the blood is always connected to the patient, there is no risk of mismatched blood due to clerical error—a small but acknowledged risk in other transfusions, even autologous donations in which patients set aside their own blood in advance.
He advocates the technique, as well, because repeated transfusions may increase the risk of infections and potentially suppress the immune system of the patient, possibly even increasing risk of recurrence among cancer patients.
With blood supplies shrinking, Jabbour compares blood to another globally precious resource: oil. “The public sees oil as plentiful, safe and inexpensive, so little effort is made toward the conservation, improvement or development of alternatives to oil.
“In the same way as oil, though, blood is a limited resource, is expensive and may pose a significant risk to health.”
Bloodless breakthroughs
USC surgeons and physicians are known pioneers in transfusion-free techniques. In 1999, a Keck School of Medicine team involving Jabbour, Yuri Genyk, M.D., assistant professor of medicine, and Rick Selby, M.D., professor of surgery and chief of the division of hepatobiliary/pancreatic surgery and abdominal organ transplantation, performed the first bloodless liver transplant in the world involving a living adult donor. Done at USC University Hospital, the successful procedure involved two brothers from Arizona, one of whom had a rare, debilitating disease of the liver’s bile ducts.
The feat was a reflection of the broad reach of bloodless techniques, which are now used not only for surgical treatment of problems of the liver, pancreas and the biliary tree, but also in cardiac, orthopaedic, vascular, thoracic and plastic surgery and neurosurgery. About 100 Keck School physicians participate in the transfusion-free program. Because bloodless surgery is so complex, it requires cooperation by specialists from anesthesiology to hematology to work successfully.
Jabbour is editing a key textbook on transfusion-free surgical techniques and has spoken about the process in Belgium, France and China, where physicians and the public are particularly aware of risks from HIV and SARS. He and fellow Keck School surgeons and physicians also authored an article in Annals of Surgery about their experiences with bloodless, living-donor liver transplants. After finding no differences in outcome or side effects for patients undergoing bloodless transplant procedures, compared to standard procedures, the team suggested that blood-preserving techniques take on broader acceptance within all surgical practices.
“In the future, we see bloodless surgery as the standard of care for patients,” says Jabbour. “Avoiding blood loss and using blood products judiciously just makes for better surgery and better patient care.”
For more information about transfusion-free surgery, contact Randy Henderson at 1-800-USC-CARE (1-800-872-2273).
in the blood
Human blood contains dozens of ingredients, from acetoacetate to zinc. A little less than half of blood’s volume is made up of what are known as corpuscles: red blood cells, white blood cells and platelets. The rest is plasma, a yellowish liquid containing water, hormones, salts, proteins, antibodies and other substances.
The blood primarily serves to supply parts of the body with the oxygen so critical to life via its red blood cells. Red blood cells carry oxygen through hemoglobin, a complex molecule containing iron, which temporarily grabs on to oxygen in the lungs and then drops off the oxygen when it reaches other tissues that need it.
Without enough healthy blood, the body’s organs cannot get the oxygen they need to function. The body also cannot rid itself of enough carbon dioxide, a waste product of metabolism.
just my type
Part of the challenge of blood transfusion is getting the right kind of blood to the people who need it. Patients can only safely receive donated blood if that blood is of a type compatible to their own, which puts some blood types in high demand.
Researchers at the Keck School of Medicine are doggedly trying to find a way around the limitations of blood typing. They have developed a method for turning types A, B and AB positive blood into universal type O negative blood, which can be given to almost anyone.
Jonathan Armstrong, Ph.D., assistant professor of physiology and biophysics, and Timothy Fisher, M.D., associate professor of physiology and biophysics, both at the Keck School, are the modern-day alchemists behind the transformation. Since they know the surface of red blood cells has antigens that identify the specific blood type, their trick is to coat the blood cells with polyethylene gycol, or PEG, a polymer coating that hides the blood-group antigens so that the recipient’s immune system cannot recognize the foreign blood cells.
The PEG coating is similar to a hydrogel—the substance used to make soft contact lenses. It acts as a barrier to cover the antigen while allowing oxygen and small molecules to drift in and out of the cells, preserving the cells’ normal function and metabolism.
However, the researchers discovered that one of every four normal people has an antibody to PEG. That might be because people are increasingly exposed in everyday life to this common polymer, which is used in products from cosmetics to pharmaceuticals.
For those with the antibody, the transfused blood would be toxic. “The use of the polymer coating to turn all blood into a universal blood type is not realistic,” says Armstrong.
He notes it would still be possible to use the coated blood for 75 percent of the population if a hospital tested for compatibility before infusion. But such tests can take longer than 45 minutes, and “it negates the advantages of a universal blood for those instances where you would most need it, such as emergency rooms and trauma centers.”
The finding raises bigger questions, too. Today, many drugs are chemically linked to PEG. In some chemotherapies, for example, conjugating a drug with PEG reduces its toxicity to the patient and keeps the drug in the system longer. Armstrong and Fisher wonder what happens to these drugs in patients who have PEG antibodies.
In the meantime, the team continues to work on its approach, noting that its PEG-treated blood might have niche applications in autoimmune hemolytic anemia and diseases such as sickle cell anemia, where chronic transfusion therapy is a mainstay in the management of the disease. And they are investigating other polymers to coat red blood cells.
Armstrong and Fisher are not alone in their quest to overcome the hazards of blood transfusion. Following a different route to address these serious problems, numerous companies are trying to develop artificial blood or blood substitutes. Their success would benefit everyone by eliminating the risks of mistyping blood and relieving blood supply shortages.
Monika Guttman contributed to this article
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