Blood types and transfusion
Red cells carry blood group antigens in their glycocalyx.
Part 1 · Clinical hook
Why this matters
Mr. Adams, 45, arrives after a car crash, bleeding heavily. There is no time to find out his blood type, so the trauma team starts O-negative red cells at once. Twenty minutes later the lab reports that he is A positive, and the team switches to A-positive units. Why is O negative safe for a stranger, and why switch as soon as the type is known? The answers lie in the antigens on red cells and the antibodies in plasma.
Part 2 · Foundations
What this builds on
Part 3 · Prerequisite check
Quick check before you start
1. What is the glycocalyx?
- The layer of sugar chains on a cell's outer surface
- The protein skeleton just under the membrane
- The fluid inside the nucleus
Show the answer
The glycocalyx is the coat of sugar chains attached to membrane proteins and lipids on the outer surface. It carries a cell's identity markers.
- Correct: The layer of sugar chains on a cell's outer surface:
- The protein skeleton just under the membrane:
- The fluid inside the nucleus:
2. What does an antibody bind?
- Any foreign cell it meets
- One specific antigen
- Oxygen
Show the answer
Each antibody's binding sites fit one antigen's shape, the way a key fits one lock.
- Any foreign cell it meets:
- Correct: One specific antigen:
- Oxygen:
3. When many red cells are destroyed at once, which pigment builds up and can cause jaundice?
- Bilirubin
- Ferritin
- Erythropoietin
Show the answer
Heme from destroyed red cells is converted to bilirubin. If the liver cannot clear it fast enough, it builds up and yellows the skin and eyes.
- Correct: Bilirubin:
- Ferritin:
- Erythropoietin:
Part 4 · Anatomy panel
Anatomy

With labels hidden, select a box to reveal its label.
Part 5 · Causal chain
How it works, step by step
- Type B red cells are transfused by mistake into a type A patient, whose plasma holds anti-B.Anti-B antibodies bind the B antigens on the donor cells within seconds.
- Each antibody has several binding sites and binds antigens on two or more cells.The donor cells are cross-linked into clumps: agglutination.
- Antibodies bound to the cells switch on plasma proteins that punch holes in their membranes.The donor cells burst (hemolysis) and release hemoglobin into the plasma.
- Free hemoglobin and chemical signals from the attack flood the blood.Fever, chills, back pain, dark urine and falling blood pressure follow, and the kidneys can fail: a transfusion reaction.
Part 6 · Key ideas
Key ideas
- The Rh factor is the D antigen, a protein in the red cell membrane, named for the rhesus monkeys in which a related antigen was first studied. An Rh positive person's red cells carry it and need only one working gene copy; an Rh negative person's red cells lack it. Unlike ABO, an Rh negative person makes anti-D antibodies only after exposure to Rh positive red cells.
- Hemolytic disease of the newborn (HDN) is the destruction of a fetus's red cells by its mother's antibodies; its most severe form is caused by the Rh factor. An Rh negative mother carrying an Rh positive fetus begins making anti-D when fetal red cells enter her blood, mostly at birth. In a later pregnancy her anti-D crosses to the fetus and attacks its Rh positive red cells.
Part 7 · Core concept
Core concepts
Part 8 · Misconception
A common mistake
The wrong idea: An Rh-negative person has anti-D antibodies from birth, just as a type A person has anti-B.
What actually happens: Anti-A and anti-B appear in infancy without any exposure to other blood. Anti-D does not: an Rh-negative person makes it only after meeting Rh-positive red cells, through a transfusion or a pregnancy. That is why a first Rh-mismatched transfusion usually causes no immediate reaction, why a first Rh-positive baby is usually unharmed, and why the injection of anti-D after delivery, which stops the mother making her own, works.
Part 9 · Retrieval check
Check yourself
Anything you miss goes into your review queue.
1. A typing test shows agglutination in the anti-A and anti-B wells and none in the anti-D well. What is the blood type?
- O positive
- AB negative
- AB positive
- O negative
Show the answer
Clumping with anti-A and anti-B means the red cells carry both A and B antigens: type AB. No clumping with anti-D means no D antigen: Rh negative.
- O positive: Type O cells carry neither A nor B, so they would not clump with anti-A or anti-B.
- Correct: AB negative: Correct. A and B present, D absent.
- AB positive: An Rh-positive sample would clump in the anti-D well too.
- O negative: Type O cells would stay smooth in all three wells if Rh negative.
2. A patient is O positive. Which red cells can she safely receive?
- O negative and O positive only
- O positive, but not O negative
- Any Rh-positive type
- O, A and B, as long as they are Rh positive
Show the answer
Her plasma holds anti-A and anti-B, so she can receive only red cells with neither antigen: type O. As an Rh-positive person she makes no anti-D, so either Rh-positive or Rh-negative O cells are safe.
- Correct: O negative and O positive only: Correct. Only type O cells, of either Rh type.
- O positive, but not O negative: O negative is also safe: it lacks the D antigen, which she already has.
- Any Rh-positive type: A, B and AB red cells would meet her anti-A or anti-B.
- O, A and B, as long as they are Rh positive: Her anti-A and anti-B would attack A and B red cells whatever their Rh type.
3. A type A patient is mistakenly given a unit of type B red cells. Predict the change in each variable over the first hour, compared with before the transfusion.
| Variable | Change |
|---|---|
| Agglutination of the donor red cells | — |
| Free hemoglobin in the plasma | — |
| Hemoglobin in the urine | — |
| Body temperature | — |
| Blood pressure | — |
| Blood type of the patient's own red cells | — |
Show the answer
An ABO-incompatible transfusion sets off an immediate antibody attack on the donor cells. Agglutination and hemolysis release hemoglobin into the plasma and urine, and the reaction causes fever and a fall in blood pressure. The transfusion must be stopped at once.
- Agglutination of the donor red cells: up. The patient's anti-B binds the B antigens on the donor cells and cross-links them into clumps.
- Free hemoglobin in the plasma: up. Antibodies on the donor cells trigger plasma proteins that burst them, releasing hemoglobin into the plasma.
- Hemoglobin in the urine: up. Free hemoglobin in the plasma is small enough to be filtered by the kidneys and spills into the urine, darkening it.
- Body temperature: up. Chemical signals released during the antibody attack cause fever and chills.
- Blood pressure: down. Signals released in the reaction widen blood vessels, so pressure falls and shock can follow.
- Blood type of the patient's own red cells: no change. The reaction destroys the donor cells. The patient's own cells stay type A.
4. An Rh-negative man who has never had a transfusion is given Rh-positive, ABO-matched red cells in an emergency. What is most likely to happen?
- An immediate, severe transfusion reaction
- Nothing now, but he may make anti-D for next time
- He becomes Rh positive permanently
- Nothing now or later: Rh does not matter in men
Show the answer
He has no anti-D yet, so the donor cells are not attacked at once. Over the next weeks his immune system may make anti-D against the D antigen he has met. A later Rh-positive transfusion could then trigger a reaction.
- An immediate, severe transfusion reaction: An immediate reaction needs antibodies already present. Anti-D forms only after exposure.
- Correct: Nothing now, but he may make anti-D for next time: Correct. The first exposure sensitizes; the danger comes later.
- He becomes Rh positive permanently: Transfused cells live about 120 days at most; his own red cells stay Rh negative.
- Nothing now or later: Rh does not matter in men: Rh matters for any future transfusion. In men there is no pregnancy risk, which is why O-positive blood is often used for men in emergencies.
5. An Rh-negative woman had an Rh-positive first baby three years ago and received no treatment. She is now pregnant with a second Rh-positive fetus, which becomes severely anemic before birth. What is the cause?
- The fetus has inherited an enzyme defect from its father
- The fetus's own antibodies attack its red cells
- Her anti-A antibodies cross to the fetus
- Anti-D from her first delivery destroys its red cells
Show the answer
Fetal red cells entered her blood at the first delivery, and she made anti-D. That kind of antibody crosses from mother to fetus. In this Rh-positive fetus, it binds and destroys red cells: hemolytic disease of the newborn.
- The fetus has inherited an enzyme defect from its father: The history of a first Rh-positive baby without treatment points to maternal anti-D, not an inherited enzyme defect.
- The fetus's own antibodies attack its red cells: A fetus does not attack its own antigens; the antibodies come from the mother.
- Her anti-A antibodies cross to the fetus: The problem here is Rh, not ABO, and most anti-A cannot cross to the fetus.
- Correct: Anti-D from her first delivery destroys its red cells: Correct. Maternal anti-D from the first pregnancy.
6. An Rh-negative woman has just delivered an Rh-positive baby. Why is she given an injection of anti-D immune globulin within 72 hours?
- To give her newborn baby a supply of antibodies against infection
- To clear fetal Rh-positive cells before she reacts to them
- To turn her red cells Rh positive
- To destroy any anti-D she already has
Show the answer
The injected anti-D clears the fetal Rh-positive cells that entered her blood at delivery before her immune system responds to them, so she never starts making her own anti-D. The injected antibody is gone within months and does not harm later pregnancies.
- To give her newborn baby a supply of antibodies against infection: The injection is for the mother, and it does not protect the baby against infection.
- Correct: To clear fetal Rh-positive cells before she reacts to them: Correct. It prevents her from becoming sensitized.
- To turn her red cells Rh positive: Nothing changes her own red cells' Rh type.
- To destroy any anti-D she already has: Anti-D cannot destroy anti-D. Once she has made her own, the injection no longer helps.
7. A student says that when mismatched blood agglutinates, it is clotting. What is the key difference?
- Agglutination needs platelets; clotting does not
- Agglutination happens outside the body; clotting happens inside it
- Antibodies clump cells in agglutination; fibrin forms a clot
- There is no difference: they are two names for one and the same process
Show the answer
Agglutination is an immune process: antibodies bind antigens on several cells and cross-link them into clumps. Coagulation is thrombin converting fibrinogen into fibrin threads. They can happen together in a severe transfusion reaction, but they are different processes.
- Agglutination needs platelets; clotting does not: Platelets are central to clotting, not to agglutination.
- Agglutination happens outside the body; clotting happens inside it: Agglutination happens inside the vessels in a transfusion reaction as well as in a typing test.
- Correct: Antibodies clump cells in agglutination; fibrin forms a clot: Correct. Different molecules, different mechanisms.
- There is no difference: they are two names for one and the same process: They involve different molecules and are triggered differently.
Part 10 · Summary
Summary
Red cells carry blood group antigens in their glycocalyx. In the ABO system, the A and B antigens are sugars added to the H antigen: type A has A, type B has B, type AB has both, type O has neither. From infancy, plasma holds antibodies against the ABO antigens the cells lack. Agglutination is antibodies cross-linking red cells into clumps, often followed by hemolysis; typing tests read it with anti-A, anti-B and anti-D. The Rh factor is the D antigen; Rh-negative people make anti-D only after exposure to Rh-positive cells. Donor red cells must not carry an antigen the recipient has, or will make, antibodies against: O negative is the universal donor and AB positive the universal recipient for red cells, and a crossmatch confirms each unit. An ABO-incompatible transfusion causes a transfusion reaction: agglutination, hemolysis, fever, dark urine, low blood pressure and kidney damage. In hemolytic disease of the newborn, an Rh-negative mother sensitized by a first Rh-positive baby makes anti-D that crosses to a later Rh-positive fetus and destroys its red cells; anti-D immune globulin prevents it.
Part 11 · Up next
What comes next
Part 12 · Connections