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Hemolytic Anaemias: Autoimmune vs Hereditary

TL;DR

Hemolytic Anemias: Autoimmune vs. Hereditary is a high-yield MRCP Part 1 topic centred on distinguishing immune-mediated destruction from intrinsic red cell defects. Autoimmune haemolysis is Coombs-positive and typically acquired, whereas hereditary causes are Coombs-negative and often lifelong. The exam frequently tests subtle lab clues such as reticulocytosis, LDH, and peripheral smear findings. Clear pattern recognition is key to scoring consistently in haematology MCQs.


Why this matters

Haemolytic anaemias are a recurring theme in MRCP Part 1, often appearing as data interpretation questions or short clinical vignettes. Candidates are expected to differentiate rapidly between autoimmune haemolytic anaemia (AIHA) and hereditary haemolytic disorders using minimal but high-yield clues.

This distinction directly influences management: autoimmune causes require immunosuppression, while hereditary conditions often involve supportive care or splenectomy. For a broader exam strategy, review the MRCP Part 1 overview.


Core sections

1. Classification Overview

Haemolytic anaemias can be broadly divided into:

  • Autoimmune (extrinsic, acquired)

    • Caused by antibodies targeting red blood cells

  • Hereditary (intrinsic defects)

    • Membrane defects (e.g. hereditary spherocytosis)

    • Enzyme deficiencies (e.g. G6PD deficiency)

    • Haemoglobinopathies (e.g. sickle cell disease)

2. High-Yield Comparison Table

Feature

Autoimmune Haemolytic Anaemia

Hereditary Haemolytic Anaemia

Cause

Antibody-mediated destruction

Genetic defect

Coombs test

Positive

Negative

Onset

Acute or subacute

Chronic/lifelong

Family history

Usually absent

Often present

Peripheral smear

Spherocytes (warm AIHA)

Variable (target cells, sickle cells)

Splenomegaly

Common

Common

Treatment

Steroids, rituximab

Supportive ± splenectomy

Examples

Warm AIHA, cold agglutinin disease

HS, G6PD deficiency, sickle cell

3. Five Most Tested Subtopics

1. Warm vs Cold Autoimmune Haemolysis

  • Warm AIHA (IgG)

    • Extravascular haemolysis (spleen)

    • Associated with autoimmune disease, lymphoma

  • Cold agglutinin disease (IgM)

    • Intravascular haemolysis

    • Triggered by cold exposure

Exam tip: Acrocyanosis + winter symptoms strongly suggest cold agglutinin disease

2. Hereditary Spherocytosis

  • Defect in cytoskeletal proteins (spectrin, ankyrin)

  • Leads to membrane loss → spherocytes

  • Features:

    • Anaemia

    • Jaundice

    • Splenomegaly

Classic triad = anaemia + jaundice + splenomegaly

3. G6PD Deficiency

  • X-linked recessive

  • Oxidative stress → haemolysis

Triggers:

  • Infections

  • Drugs (e.g. sulfonamides, antimalarials)

  • Fava beans

Exam clue: Bite cells and Heinz bodies

4. Sickle Cell Disease

  • β-globin mutation → HbS

  • Sickling in hypoxia → vaso-occlusion

Key features:

  • Pain crises

  • Autosplenectomy

  • Increased infection risk

5. Laboratory Markers of Haemolysis

Across haemolytic anaemias:

  • ↑ LDH

  • ↑ unconjugated bilirubin

  • ↓ haptoglobin

  • ↑ reticulocyte count

Key discriminator:

  • Positive Coombs test → autoimmune

  • Negative Coombs → hereditary or non-immune

4. 10 High-Yield Exam Points

  1. Coombs-positive = autoimmune haemolysis

  2. Coombs-negative = hereditary or non-immune cause

  3. Spherocytes are not specific (seen in AIHA and HS)

  4. G6PD deficiency causes episodic haemolysis

  5. Cold agglutinin disease worsens in cold weather

  6. Splenectomy improves hereditary spherocytosis

  7. Reticulocytosis confirms marrow response

  8. Dark urine indicates intravascular haemolysis

  9. Pigment gallstones are common in chronic haemolysis

  10. Drugs can trigger both AIHA and G6PD crises


Practical examples / mini-cases

Mini-MCQ

A 32-year-old woman presents with fatigue and jaundice. Blood tests show:

  • Hb: 8.2 g/dL

  • Reticulocytes: elevated

  • LDH: raised

  • Haptoglobin: low

  • Direct Coombs test: positive

What is the most likely diagnosis?

Answer: Warm autoimmune haemolytic anaemia

Explanation: The positive Coombs test confirms immune-mediated haemolysis. Raised LDH and low haptoglobin support active red cell destruction. In hereditary conditions, the Coombs test would be negative.


Medical student revising haemolytic anaemias for MRCP Part 1 with notes and laptop

Common pitfalls (5 bullets)

  • Confusing hereditary spherocytosis with AIHA due to shared spherocytes

  • Ignoring the Coombs test, the single most important discriminator

  • Missing drug triggers in G6PD deficiency

  • Overlooking cold exposure history in cold agglutinin disease

  • Forgetting that reticulocytosis is essential evidence of haemolysis


FAQs

1. How do you quickly differentiate autoimmune from hereditary haemolytic anaemia?

Use the direct Coombs test. A positive result indicates autoimmune haemolysis, while a negative result suggests hereditary or other non-immune causes.

2. Why are spherocytes seen in both AIHA and hereditary spherocytosis?

Both involve red cell membrane loss. In AIHA, it is immune-mediated; in hereditary spherocytosis, it is due to structural protein defects.

3. What are common triggers of haemolysis in G6PD deficiency?

Infections, oxidative drugs (e.g. sulfa drugs), and fava beans are classic triggers leading to episodic haemolysis.

4. What is the role of splenectomy in haemolytic anaemia?

It is mainly used in hereditary spherocytosis to reduce red cell destruction in the spleen.

5. Which haemolytic anaemia is associated with cold exposure?

Cold agglutinin disease, mediated by IgM antibodies, is triggered by cold temperatures and may cause acrocyanosis.


Ready to start?

Haemolytic anaemias are best mastered through repeated exposure to exam-style questions. Strengthen your understanding with targeted practice using our Free MRCP MCQs or simulate exam conditions with a Start a mock test.

For deeper conceptual clarity, complement this topic with structured video content in our MRCP lectures and integrate with related haematology revision posts.


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