A look at the life-saving work of a Bristol lab.
Her blood arrived in a sample bag a couple of hours before me, from the hospital in Stockholm, Sweden.
Ms X was in the throes of a painful sickle cell crisis, her abnormally rigid, sickle-shaped red blood cells clogging up her small blood vessels. She needed a blood transfusion; however, hospital blood tests show that Ms X, originally from Gambia, has made antibodies against blood group antigens – molecules found on the surface of red blood cells – but they can’t identify which ones. (We make antibodies against proteins on other people’s blood if it’s incompatible with our own. This can cause what’s known as a transfusion reaction.)
The International Blood Group Reference Laboratory (IBGRL) in Bristol, England is one of the world-leading places for identifying complex mixtures of antibodies. When I arrive in the lab there, Tom Bullock, Reference Serology Manager, has already given Ms X’s blood a spin in the centrifuge to separate the red blood cells from the antibody-containing plasma.
His next step is to screen her plasma for antibodies against the Duffy blood group system, which are common in Europe but rarer in African populations. He selects samples of Duffy-positive and Duffy-negative red blood cells from the lab’s rare blood fridge, pipettes a drop from each into a test-tube and adds a drop of Ms X’s plasma.
The grainy clotting (agglutination) in the test-tubes shows that the cells possess an antigen that is reacting with Ms X’s plasma. Further investigations show that an antibody directed to an antigen in the Duffy blood group system is present, but additional reactions that cannot be accounted for indicate that other antibodies may be present.
One might be an antibody in the Dombrock system. To test this we need to use some of the very rare blood, which is kept frozen in nitrogen in a separate room downstairs. There are oxygen monitors around the wall, and other safety and monitoring equipment; nitrogen gas is heavier than air, and a spillage nearby could displace the air around us.
Some of the cells stored in these tanks, shrouded in dense clouds of nitrogen, are decades old, taken from patients and donors as far back as the 1970s. This blood comes from several places. If a patient referred to the IBGRL is found to have rare blood, their blood can be stored for future use to identify patients with the same rare blood. There is also an international network of people working in rare blood, who exchange rare cells for reference collections.
Using this blood is a decision that isn’t taken lightly, because there may never be another patient or donor once a particular sample has been used up. “We can’t afford to waste a single drop,” says Nicole Thornton, Head of Red Cell Reference at the IBGRL. “That’s why we have to plan each stage of the investigation so carefully.”
Back upstairs, Bullock thaws the tiny balls of frozen very rare blood and mixes them with Ms X’s plasma. Because antibodies can be hidden in complicated patterns of reactivity, he searches for clues to their nature by testing at different temperatures and in the presence of certain carefully selected enzymes. Some antibodies react more vigorously against blood cell antigens at higher or lower temperatures, and different enzymes can destroy one type of antigen while enhancing another.
By the end of the day, we haven’t solved the mystery of Ms X’s blood. But Bullock has found a number of blood types that don’t react with her serum, so the Swedish hospital is nearer to being able to find safe blood for her.
A few days later, he’s pinned down the culprits. As well as making an antibody to an antigen in the Duffy system, Ms X had made antibodies to two antigens in the Knops system. Fortunately for her, neither of the latter were clinically significant.