The Science of Why Blood Transfusions Are So Tricky

How blood differs from person to person — and person to animal

Red blood cells misleadingly look the same at first.Photo byGerd Altmann from Pixabay

Blood, that icky red liquid we all prefer to keep mostly inside our bodies, is not unique to humans. All mammals, reptiles, birds, fish, and amphibians have iron-rich red blood flowing through their veins and arteries.

But human blood isn’t the same as, say, pig blood. They both look the same to the naked eye, but they aren’t interchangeable.

We cannot use animal blood for a transfusion in surgery. And we can only receive transfusions from people with the same blood type as us.

Why? What makes different types of blood, well, different? And how can we tell the origin of a sample of blood?

Blood is actually really complex

Blood looks like a uniform red goo. Despite the myth, human blood is never blue. It can look blue in our veins — thanks to our skin absorbing more red light than blue light — and veins are often colored blue in drawings in anatomy textbooks to distinguish them from arteries.

But whether in our bodies or out, blood is red.

And when viewed through a microscope, blood is a complex blend of many different types of cells.

The most common cell in our blood is the red blood cell. As the name suggests, it’s red, due to the presence of iron in a molecule called hemoglobin. (And, you might’ve guessed, there are no blue blood cells.) The iron helps oxygen bind to this molecule, so red blood cells can ferry the oxygen around to the rest of our body.

A little less than half our blood, by volume, is red blood cells. The recipe looks like this:

• 50–60% of the mix: plasma, a blend of water, proteins, antibodies, sugars, and fats.
• 40–50% of the mix: red blood cells.
• And about 1% of the mix: everything else, including various types of white blood cells and platelets, little pieces of cells that help blood stick together and clot when exposed to air, in order to seal up wounds.

Each of these elements is distinct to the organism from which it comes. Red blood cells are the biggest overall differentiator.

ABO, not ABBA

Red blood cells are fascinating. They have a very limited lifespan, only lasting a couple of months, so the body is constantly producing more. They spawn off of huge stem cells that permanently live inside bone marrow. Red blood cells stream out of our bones like freshly built cars constantly rolling out of a factory.

When they first bud off from the stem cell, immature red blood cells have a nucleus, a central compartment that holds the cell’s DNA instructions. But as they mature, they actually lose the nucleus, in order to make room for even more oxygen-carrying hemoglobin. The mature red blood cells floating in our bloodstream are just pale imitations of regular cells, like tiny zombies.

But red blood cells do retain some features beyond “bag full of hemoglobin.” They keep certain molecules embedded in their membrane, which help our white blood cells recognize them as friendly.

The membranes of red blood cells get studded with attachments by various enzymes. One particular enzyme, called a glycosyltransferase, comes in 2 forms: form A, and form B.

• If a person’s body makes glycosyltransferase version A, they have type A blood.
• If a person’s body makes glycosyltransferase version B, they have type B blood.
• If a person’s body makes both types, glycosyltransferase A and B, they have type AB blood.
• If a person’s body doesn’t make any glycosyltransferase enzymes at all, they have type O blood.

There’s another group of proteins, called Rhesus (Rh) factors, which are also either present or absent depending on your genetics. The most commonly measured Rh factor is type D. People who have type D have “positive” blood, while those without it have “negative” type blood.

Put it all together: if someone has an A+ blood type, their body makes glycosyltransferase version A and the Rh(D) factor, which both show up on the exterior of their red blood cells.

Human vs. animal blood — how can we tell?

What about our blood, versus blood from other species? Human and animal blood doesn’t look different to the naked eye, and it’s got the same fractions of different cell types. Other mammals’ blood is also made of plasma, red blood cells, and a tiny fraction of white blood cells, platelets, and other ingredients.

But at the molecular level, blood from other animals is very different from human blood. The red blood cells have different proteins and attachments coating their cells, unique to that species of animal. Dogs, horses, cattle, chickens — they all have their own blood typings, distinct from human ABO.

If our own immune system sees blood cells with different surface proteins, it reacts and tries to destroy the invaders. This immune reaction can be deadly, which is why we can’t receive a blood transfusion from someone with who produces different antigens (let alone from an entirely different species).

(This is also why people with type O- blood are described as universal donors; since they don’t make any glycosyltransferase or Rhesus factor, there’s nothing to set off the recipient’s immune system alarms. Individuals with AB+ blood are universal recipients, since their immune system doesn’t care if it sees A, B, or both glycosyltransferase variants.)

In the past, we found a cool use for this immune reaction: blood testing in police work. In the early 1900s, forensic pathologists figured out how to isolate an immune serum, made from rabbit blood, that reacted specifically with human blood and human blood only. This helped detectives figure out if blood found at the scene of a suspected crime was human or not.

These days, no rabbits are needed for police investigations; newer tests shine a laser onto blood samples, measuring the wavelengths produced and identifying the specific surface proteins, to match against a database and determine the species of origin.

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Blood types are a fascinating example of how our bodies use tiny protein signals that are invisible to the naked eye. These proteins, on the surfaces of our red blood cells, reflect our uniqueness as a person and help our immune system stay alert for invaders.

Sadly, this limits the sources of blood that we can receive for transfusions or medical procedures. But good news! Ongoing research is looking into methods to strip the identifying molecules off of blood, potentially allowing blood from any person, and maybe even from animals, to be used for medical purposes.

Maybe, someday in the future, people will brag about the strength of the boar or bull blood flowing in their veins!

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