Pathology of Transfusion Reactions
Start from one first principle: a transfusion is the deliberate installation of another person's living cells and soluble plasma proteins into your patient's bloodstream. The immune system spends its whole working life sorting self from non-self, so the moment you connect a unit of donor blood you have created an immunological encounter inside the circulation. Every serious transfusion reaction is, at its root, a question of what the recipient's body recognises as foreign and how violently it reacts.
That single idea organises the entire chapter. If the recipient already carries antibody against a donor red-cell antigen, those red cells are destroyed (haemolytic reactions). If the recipient reacts to donor leukocytes, plasma proteins or accumulated mediators rather than to red cells, you get fever, allergy or lung injury without red-cell destruction. If the problem is not immunological at all, the danger is volume, contamination or stored-blood chemistry. And because antibodies take time to form, some reactions strike within minutes while others surface days later. Build every reaction back to "what is being recognised, and when" and the long differential becomes a short logic.
Transfusion is genuinely lifesaving in obstetric haemorrhage and severe anaemia. The skill the Primary candidate must build is not fear of transfusion but the ability to connect a clinical pattern at the bedside to the mechanism driving it. The table below is the destination, not the starting point — read it after the first-principles sections that follow, then return to it.
The core Primary task is to connect the clinical pattern to the mechanism:
| Clinical pattern during or after transfusion | Mechanism to consider first |
|---|---|
| Fever, rigors, flank/back pain, hypotension, haemoglobinuria | Acute haemolytic transfusion reaction until proven otherwise |
| Fever/rigors without haemolysis or instability | Febrile non-haemolytic reaction after excluding dangerous causes |
| Urticaria/itch only | Mild allergic reaction |
| Wheeze, angioedema, hypotension, collapse | Anaphylaxis or severe allergic reaction |
| Hypoxia with bilateral infiltrates and no overload | TRALI |
| Hypoxia with hypertension, raised filling pressure, positive fluid balance | TACO |
| Fever, shock and contaminated product concern | Transfusion-transmitted bacterial sepsis |
| Falling Hb, jaundice days later | Delayed haemolytic reaction |
This chapter is the pathology foundation. Blood-product selection and obstetric haemorrhage workflows belong in Finalpostpartum haemorrhage, while alloimmunisation and fetal implications are covered in FinalRhesus alloimmunisation.
The Immune Building Blocks You Need First
Before classifying reactions, fix four pieces of immunology in place. They are the only tools you need to reason through every reaction that follows.
Antigens and antibodies. A red cell, leukocyte or platelet displays surface proteins and sugars — antigens. An antibody (immunoglobulin) is a Y-shaped protein with a binding site uniquely shaped to one antigen. When recipient antibody meets a matching donor antigen, the two lock together and a destructive cascade can begin. The recipient's antibodies are what make donor blood dangerous, not the donor blood itself.
Two antibody classes do most of the damage. IgM is a large pentamer that is extremely good at activating complement; it drives the fast, violent reactions. IgG is a smaller monomer that usually marks cells for slower destruction and is the antibody of immunological memory; it drives the delayed, milder reactions. Knowing which class is involved predicts how a reaction will look.
Complement is the amplifier. Complement is a cascade of plasma proteins that switches on when antibody (especially IgM) coats a cell surface. Its end product, the membrane attack complex, can punch holes directly in red cells inside the vessel (intravascular haemolysis). Along the way it releases anaphylatoxins (C3a, C5a) that trigger fever, vasodilatation and shock. Complement is why an ABO mismatch is an emergency and a Kidd antibody usually is not.
Where a cell dies matters. Antibody-coated cells can be destroyed two ways. Intravascular haemolysis is complement bursting cells inside the bloodstream, spilling free haemoglobin into plasma and urine — fast, dangerous, ABO-type. Extravascular haemolysis is macrophages in the spleen and liver eating antibody-coated cells more quietly — slower, jaundice rather than haemoglobinuria, the delayed-reaction picture.
Memory explains the delay. The first time the immune system meets a foreign antigen it responds slowly and weakly (a primary response). Re-exposure triggers a rapid, vigorous secondary response from memory B cells. This is why a woman sensitised by an earlier pregnancy or transfusion can have an antibody too faint to detect at crossmatch that surges days after re-exposure — the basis of delayed haemolysis and of alloimmunisation that complicates future pregnancies.
With those five ideas — antigen/antibody recognition, IgM versus IgG, complement, intravascular versus extravascular destruction, and immunological memory — every reaction below is a recombination you can predict rather than a list to memorise.
Classification
Transfusion reactions are best classified by timing and mechanism.
| Class | Timing | Main pathology | Examples |
|---|---|---|---|
| Acute immune | During transfusion or within 24 hours | Antibody, complement, mast-cell or leukocyte activation | Acute haemolytic reaction, febrile non-haemolytic reaction, allergy, anaphylaxis, TRALI |
| Acute non-immune | During transfusion or within 24 hours | Volume, temperature, citrate, potassium, contamination | TACO, bacterial sepsis, hypocalcaemia, hyperkalaemia, hypothermia |
| Delayed immune | Days to weeks | Anamnestic antibody or cellular immune reaction | Delayed haemolysis, post-transfusion purpura, transfusion-associated graft-versus-host disease |
| Delayed non-immune/infectious | Days to years depending agent | Transmitted infection or iron accumulation | Viral/parasitic transmission, iron overload after repeated transfusion |
Fever is the key trap: it may be benign, but it is also an early sign of haemolysis or bacterial contamination. The safe pathology answer is to treat fever during transfusion as dangerous until the blood bank and clinical assessment exclude haemolysis and sepsis.
Compatibility as Immunopathology
Red-cell transfusion is dangerous when the recipient has antibodies that recognise donor red-cell antigens. The ABO system is uniquely dangerous because of a quirk that breaks the usual rule of immunology: people develop anti-A and anti-B antibodies without ever having been transfused. These naturally occurring antibodies (so-called isohaemagglutinins) arise in infancy from exposure to similar carbohydrate structures on gut bacteria and food, so a group O adult already has high-titre anti-A and anti-B circulating, mostly as complement-fixing IgM, before any blood is ever given. That is why an ABO-incompatible unit can trigger violent intravascular haemolysis on first exposure, with no prior sensitising event — there is no slow primary response to wait for. Every other clinically important red-cell antibody (Rh, Kidd, Duffy, Kell) instead has to be made after exposure through pregnancy or transfusion, which is why those reactions are usually delayed rather than immediate.