[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Red cells and bleeding disorders](https://durgical.com/en/general-pathology/areas/red-cells/) › Immunohaemolytic anaemia

# Immunohaemolytic anaemia

- Lesion

Antibodies stick to red cells and mark them for destruction. Whether they act warm or cold decides where and how the cells die.

Updated Nov 12, 2026

## Key points

- The direct Coombs test detects antibody or complement on the patient's red cells; the indirect test detects antibodies in serum.
- Warm type: IgG, extravascular haemolysis in the spleen, spherocytes, splenomegaly.
- Drug mechanisms: hapten (penicillin, cephalosporins) or tolerance-breaking autoantibodies (α-methyldopa).
- Cold agglutinins: IgM, agglutination in fingers, ears and nose (acrocyanosis, Raynaud), C3b-mediated removal by liver macrophages.
- Paroxysmal cold haemoglobinuria: IgG against the P antigen binds in the cold and lyses with complement on warming, usually in children after viral infections.

## What it is

Immunohaemolytic anaemias are caused by antibodies, sometimes with complement, bound to red cells. Warm antibodies (usually IgG, active at body temperature) are the commonest; they coat cells that macrophages partly eat, creating spherocytes. They can be idiopathic or secondary to lupus, CLL and other lymphomas, or drugs. Cold agglutinins (IgM) bind in cool peripheral vessels and fix complement; they appear briefly after Mycoplasma or EBV infection or chronically with B-cell neoplasms. Cold haemolysins (IgG Donath–Landsteiner antibody) cause paroxysmal cold haemoglobinuria. Alloantibodies cause transfusion reactions and haemolytic disease of the newborn.

## Step by step

- Warm: an IgG autoantibody binds a red cell antigen (often Rh) at body temperature.
- Warm: Fc receptors on splenic macrophages grab the cell and nibble membrane, making spherocytes, then destroy them.
- Cold: IgM binds in cool extremities, agglutinates cells and fixes complement.
- Cold: on warming IgM falls off, but C3b remains and liver macrophages remove the cells.
- Cold haemolysin: IgG binds in the cold and fixes complement that completes lysis when the blood returns to the warm core.

## Types of immunohaemolytic anaemia

| Type | Antibody | Main causes | Where cells are destroyed |
| --- | --- | --- | --- |
| [Warm antibody](https://durgical.com/en/conditions/autoimmune-haemolytic-anaemia/) | IgG (sometimes IgA), active at body temperature | Idiopathic, lupus, CLL and other lymphomas, drugs | Spleen (extravascular) |
| [Cold agglutinin](https://durgical.com/en/conditions/autoimmune-haemolytic-anaemia/) | IgM, active in the cold | Mycoplasma pneumoniae, EBV, CMV, HIV; B-cell neoplasms; idiopathic | Liver and spleen via C3b; mild intravascular |
| Cold haemolysin (paroxysmal cold haemoglobinuria) | IgG Donath–Landsteiner against P antigen | Children after viral infections; historically syphilis | Intravascular, complement-mediated |
| Drug-induced | IgG against drug-coated cells or true autoantibody | Penicillin, cephalosporins, α-methyldopa | Mostly spleen |

## Clinical notes

- Anaemia with spherocytes and a positive direct Coombs test; look for lupus, lymphoma or a drug.
- Cold agglutinin disease: symptoms worse in cold weather; blood may agglutinate in the sample tube.
- Rh alloimmunization causes haemolytic disease of the fetus and newborn.

## In the lab

- Direct antiglobulin test with anti-IgG and anti-C3 reagents; cold agglutinin titre; Donath–Landsteiner test.

## Memory aid

Warm is IgG and the spleen; cold is IgM, complement and the liver; Donath–Landsteiner binds in the cold and bursts in the warm.

## Test yourself

Think of the answer, then tap the question to see it.

## Which infection classically produces transient cold agglutinins?

Mycoplasma pneumoniae (also EBV infectious mononucleosis).

## Why do warm autoimmune haemolytic anaemias show spherocytes?

Splenic macrophages remove pieces of membrane from IgG-coated cells, leaving smaller spheres.

## What does the direct Coombs test detect?

Immunoglobulin or complement already bound to the patient's red cells.

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## Elsewhere in DurgiPedia

- [Type II hypersensitivity (antibody against cells)](https://durgical.com/en/immunology/type-ii-hypersensitivity/)
- [ABO and Rh blood groups, hemolytic disease of the newborn](https://durgical.com/en/immunology/abo-and-rh-blood-groups-hemolytic-disease-of-the-newborn/)
- [Complement: three pathways, MAC, regulators](https://durgical.com/en/immunology/complement-three-pathways-mac-regulators/)

## Connections

## Related 4

- [Haemolysis: extravascular vs intravascular](https://durgical.com/en/general-pathology/haemolysis-extravascular-vs-intravascular/)
- [Chronic lymphocytic leukaemia (CLL/SLL)](https://durgical.com/en/general-pathology/chronic-lymphocytic-leukaemia/)
- [Fetal hydrops: immune and nonimmune](https://durgical.com/en/general-pathology/fetal-hydrops-immune-and-nonimmune/)
- [Complications of transfusion](https://durgical.com/en/general-pathology/complications-of-transfusion/)

## Related conditions 6

- [Autoimmune haemolytic anaemia](https://durgical.com/en/conditions/autoimmune-haemolytic-anaemia/)
- [Chronic lymphocytic leukaemia](https://durgical.com/en/conditions/chronic-lymphocytic-leukaemia/)
- [Systemic lupus erythematosus](https://durgical.com/en/conditions/systemic-lupus-erythematosus/)
- [Rh alloimmunisation in pregnancy](https://durgical.com/en/conditions/rh-alloimmunisation-in-pregnancy/)
- [Infectious mononucleosis](https://durgical.com/en/conditions/infectious-mononucleosis/)
- [MGUS and Waldenström macroglobulinaemia](https://durgical.com/en/conditions/mgus-and-waldenstrom-macroglobulinaemia/)

## Microorganisms 2

- [Mycoplasma pneumoniae](https://durgical.com/en/microbiology/mycoplasma-pneumoniae/)
- [Epstein–Barr virus](https://durgical.com/en/microbiology/epstein-barr-virus/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Immune hemolytic anemia: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000576.htm) (MedlinePlus, US National Library of Medicine, 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/immunohaemolytic-anaemia/