New promise for blood transfusions

Scientists have created a “stealth” red blood cell that camouflages its immune status, meaning it could potentially be a blood transfusion for anybody in an emergency, regardless of their blood type.

The finding, published in Science Advances, promises to shake up my own former field of emergency medicine, where treating people who have lost litres of blood from shootings, stabbings and road trauma is all in a day’s work.

Here’s why.

The resuscitation team has to quickly get an IV in the patient’s vein and infuse salt water to get their blood pressure back up, otherwise you’re looking at cardiac arrest and death.

But even if blood pressure is normalised there’s still an issue – salt water can’t carry oxygen around the body, so your patient might die anyway. The answer is to transfuse oxygen-carrying red blood cells, supplied by a very kind person who has donated blood.

But that comes with its own complications.

Red blood cells are host to a range of different antigens, signposts on their surface that tell antibodies and other immune cells whether they are yours or somebody else’s.

Some of those antigens are household names – A and B antigens are found on the red cells of people with blood types A and B (there’s also blood type AB, which has both).

Give a person with type A blood a transfusion of type B, or vice versa, and you get something called a transfusion reaction that makes the red cells burst and the person gets very sick or dies.

Which is where blood type “O” comes in. It hasn’t got A or B antigens and so you can give it to someone of any blood type without a reaction.

That’s helpful, but it comes with a bit of fine print.

Some blood cells also have rhesus or “D” antigens on their surface. If you have those, your blood type gets an additional “positive” moniker: A+, B+, AB+ or O+. If you don’t have the Rh antigen you are “negative”: A-, B-, AB- or O-. {%recommended 5843%}

Put Rh positive blood into someone who is Rh negative and you also risk a transfusion reaction.

Which is why O negative blood is so special. It is the “universal donor” that can be transfused into anyone – emergency doctors like to have plenty of it on hand because it takes time to crossmatch a person’s exact blood type, and in a trauma you need blood STAT.

But “O neg” blood is annoyingly rare – only about nine per cent of people have it. And when people stop donating blood, during a coronavirus epidemic for example, stockpiles can plummet.

Enter a team of researchers led by Ben Wang at Zhejiang University School of Medicine in Hangzhou, China.

They took Rh positive human red blood cells and coated them with a hydrogel sheath, anchored to the surface of the cell. Their goal was twofold: they wanted to hide the red cell’s Rh status from the immune system and do it in a way that didn’t render the cell useless in terms of carrying oxygen.

They ran the stealth cells through a battery of tests that suggests they achieved goal fulfilment.

First, they tested whether the engineered cells were made more fragile and likely to break. They weren’t. Then they checked whether the cells were still able to clot. They were.

But they also wanted to make sure the cells were not more viscous than normal red cells. That would make them prone to clot excessively, causing problems like deep venous thrombosis (DVT). The stealth red cells’ viscosity profile was healthy.

Perhaps most importantly, Wang’s group ran the robo red cell through its oxygen-carrying paces and found that it took up and delivered oxygen with almost precisely the same dynamics as a real cell.

For ultimate proof of purpose, they drained mice of ten per cent of their blood volume, then resuscitated them with stealth red cells. It worked. The mice survived and so did the red cells, which hung around in the critters for around 40 days, comparable to normal red cells.

They also infused the cells into rabbits that were primed to react to the D antigens on the robo cell surface. There was no immune reaction, suggesting D stealth was fully enabled.

The researchers say that masking the D antigen combined with other methods that hide a red cell’s A and B antigens could make it possible to manufacture O negative blood from other types.

“This study provides new hope for the generation of universal blood cells based on cell surface framework engineering,” they write.

Which will also give hope to trauma doctors and, most importantly, their patients. 

Related reading: With blood, fresh is not best