Not long ago, a precious packet of blood traveled more than 7,000 miles by special courier, from America to Australia, to save the life of a newborn. Months before the delivery date, a routine checkup of the mom-to-be had revealed that the fetus suffered from hemolytic disease. Doctors knew that the baby would need a blood transfusion immediately after delivery. The problem was, the baby's blood type was so rare that there wasn't a single compatible donor in all of Australia.
A request for compatible blood was sent first to England, where a global database search identified a potential donor in the United States. From there, the request was forwarded to the American Rare Donor Program, directed by Sandra Nance. The ARDP had compatible frozen blood on hand, but Nance knew that a frozen bag might rupture in transit. So her organization reached out to the compatible donor, collected half a liter of fresh blood, and shipped it across the Pacific. When the mother came in to give birth, the blood was waiting. “It was just magic,” Nance says.
You’re probably aware of eight basic blood types: A, AB, B and O, each of which can be “positive” or “negative.” They're the most important, because a patient who receives ABO +/– incompatible blood very often experiences a dangerous immune reaction. For the sake of simplicity, these are the types that organizations like the Red Cross usually talk about. But this system turns out to be a big oversimplification. Each of these eight types of blood can be subdivided into many distinct varieties. There are millions in all, each classified according to the little markers called antigens that coat the surface of red blood cells.
AB blood contains A and B antigens, while O blood doesn't contain either; “positive” blood contains the Rhesus D antigen, while “negative” blood lacks it. Patients shouldn’t receive antigens that their own blood lacks—otherwise their immune system may recognize the blood as foreign and develop antibodies to attack it. That’s why medical professionals pay attention to blood types in the first place, and why compatible blood was so important for the baby in Australia. There are in fact hundreds of antigens that fall into 33 recognized antigen systems, many of which can cause dangerous reactions during transfusion. One person's blood can contain a long list of antigens, which means that a fully specified blood type has to be written out antigen by antigen—for example, O, r”r”, K:–1, Jk(b-). Try fitting that into that little space on your Red Cross card.
Scientists have been discovering unexpected antigens ever since 1939, when two New York doctors transfused type O blood into a young woman at Bellevue Hospital. Type O was considered a “universal” blood type that anyone could receive, yet the woman experienced chills and body pain—clear signs that she was reacting to the blood. After running some lab tests, the doctors confirmed that even type O blood could contain previously unknown antigens. They’d accidentally discovered Rhesus antigens.
Additional kinds of antigens have been discovered every few years since then. Almost everyone has some. More than 99.9 percent of people carry the antigen Vel, for example. For every 2,500 people, there's one who lacks the Vel antigen who shouldn't receive blood from the remaining 2,499. (Like many blood types, Vel-negative is tightly linked to ethnicity, so how rare it is depends on what part of the world you’re in.) If a Vel-negative patient develops antibodies to Vel-positive blood, the immune system will attack the incoming cells, which then disintegrate inside the body. For a patient, the effects of such reactions range from mild pain to fever, shock and, in the worst cases, death.
Blood types are considered rare if fewer than 1 in 1,000 people have them. One of the rarest in existence is Rh-null blood, which lack any antigens in the Rh system. “There are nine active donors in the whole community of rare blood donors. Nine.” That's in the entire world. If your blood is Rh-null, there are probably more people who share your name than your blood type. And if you receive blood that contains Rh antigens, your immune system may attack those cells. In all, around 20 antigen systems have the potential to cause transfusion reactions.
Just to be clear, transfusion patients today don't have much to worry about. In 2012, there were tens of millions of transfusions in the United States, but only a few dozen transfusion-related deaths were reported to the U.S. Food and Drug Administration. Medical practitioners go to great lengths to make sure that transfused blood is compatible. But curiously enough, they manage to do this without even knowing all the antigens present.
Before a transfusion takes place, lab technicians mix a sample of the patient's blood with the sample of a donor whose blood type is ABO +/– compatible. If the two samples clump, the blood may be unsafe to transfuse. “The moment you discover that, you do not know why,” Nance explains. Figuring out the precise cause of the problem is like solving a crossword puzzle, she says. “You test many donors that are known types, and you find out, just by process of elimination, what is the contributing factor that makes this incompatible.”
This was the process that helped the newborn in Australia. Lab technicians there had tested the fetal blood and figured out which antigens they needed to avoid. But they still didn't know where in the world they might find suitable blood. So they sent a rare blood request to the international organization set up for cases just like this: the International Blood Group Reference Laboratory in Bristol, England. The IBGRL consults its database of hundreds of thousands of rare donors worldwide to find compatible blood. For the past 30 years, the process of global blood sharing has been gradually standardized during the biennial congress of the International Society for Blood Transfusion, which took place this week in Seoul, South Korea.
In the past two years, at least 241 packets of rare blood were shipped internationally, according to Nicole Thornton, head of Red Cell Reference at the IBGRL. Many more are shipped within national borders. In 2011, for example, more than 2,000 units of rare blood were shipped within the United States. It’s an impressive feat of coordination.
Even rare donor programs with the resources to identify and ship rare blood are looking to improve. There just aren't enough rare donors who come in regularly. The American Rare Donor Program has 45,000 rare donors in its database, but 5 percent of transfusion patients still don't get the blood they need. Coral Olsen, a scientist in charge of regional rare blood banking in South Africa, says that her laboratory often struggles to keep track of registered rare donors. “Because a lot of them are from rural settings, we often can't get ahold of them. So that's our challenge, as far as tracing and tracking and maintaining our rare donor base.”
For many countries, an even bigger challenge is simply dealing with resource constraints. National blood laboratories have to maintain a repository of samples if they want to run detailed antigen tests. Olsen says that in developing countries, where starting samples aren’t always available, it's difficult to even begin classifying and sourcing rare blood. Finally, there's the high cost of importing rare types, especially for patients who need chronic transfusions. In those cases, medical professionals sometimes have to use blood that's known to be incompatible, but unlikely to cause severe reactions because of the particular antigens involved.
One day, scientific breakthroughs may make it easier to find compatible blood for anyone. Geneticists are working on testing methods that determine blood types using DNA, without looking at the blood itself. (So far, this process only works with certain antigens.) Nance hopes that one day, every newborn will undergo testing so that blood banks can build a comprehensive database of every rare type, which would immediately point medical professionals to the nearest compatible donor. Biochemists, meanwhile, have been testing chemicals that effectively mask the antigens on red blood cells, seeking to turn them into “stealth” cells that are functionally universal.
Until then, researchers will probably go on discovering antigens one by one. It's as if the surface of red blood cells started out as a fuzzy picture that scientists have slowly brought into focus, revealing subtle differences that just weren't visible before. For blood scientists and patients with rare blood types, these differences can be tedious and troublesome. But they're also a reminder of our remarkable individuality. With hundreds of possible antigens and millions of possible antigen combinations, your blood can be as unique as your fingerprint.