# Hereditary Spherocytosis and Red Cell Membrane Disorders

> Hereditary spherocytosis for NEET-PG Medicine covering osmotic fragility, the EMA binding test, Coombs testing and when splenectomy is indicated.

- Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/hereditary-spherocytosis-and-red-cell-membrane-disorders
- Exam / course: NEET-PG · Subject: Medicine
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-08
- Last updated: 2026-10-08
- Reference basis: Dacie and Lewis Practical Haematology; Williams Hematology
- How to cite: "Hereditary Spherocytosis and Red Cell Membrane Disorders", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/hereditary-spherocytosis-and-red-cell-membrane-disorders

## Direct answer

Hereditary spherocytosis is an inherited red cell membrane disorder, most often autosomal dominant, caused by defects in ankyrin, spectrin or band 3 that make erythrocytes lose membrane surface and become spherical. The spherocytes are trapped and destroyed in the spleen, producing haemolysis with reticulocytosis, jaundice and splenomegaly. Osmotic fragility and the eosin-5-maleimide (EMA) binding test confirm the diagnosis, and splenectomy is the main definitive treatment for symptomatic anaemia.

## What you must remember

- **Genes:** ANK1 (ankyrin) is the commonest defect, with SLC4A1 (band 3) and SPTB (beta-spectrin) the other major genes.
- **Indices:** a raised mean corpuscular haemoglobin concentration, above about 36 g/dL, is a useful clue because spherocytes lack central pallor.
- **Osmotic fragility:** increased fragility on incubation in hypotonic saline, with the acidified glycerol lysis test as an alternative.
- **EMA binding test:** reduced eosin-5-maleimide binding by flow cytometry supports the diagnosis and is more sensitive and specific than osmotic fragility.
- **Coombs test:** must be negative, since autoimmune haemolytic anaemia also produces spherocytes and increased fragility.
- **Splenectomy:** deferred until after early childhood, with pneumococcal, meningococcal and Haemophilus influenzae type b vaccines first and lifelong penicillin prophylaxis afterwards; pigment gallstones are a common indication.
- **Enzyme contrast:** pyruvate kinase deficiency has normal osmotic fragility and no spherocytes, so it is a different diagnosis despite similar haemolysis.

## A worked case: jaundice and a big spleen in a child

A 12-year-old boy has recurrent jaundice, splenomegaly and a family history of anaemia, and the workup follows a fixed sequence.

1. **Read the smear:** The smear shows spherocytes, the MCHC is raised and the reticulocyte count is about 12 percent.
2. **Exclude autoimmunity:** The direct Coombs test is negative.
3. **Confirm the membrane defect:** Osmotic fragility is increased and EMA binding is reduced, which together confirm hereditary spherocytosis.
4. **Check gallstones and family:** Ultrasound looks for pigment gallstones, and a careful pedigree is useful because relatives often show mild anaemia or gallstones. The family is counselled about the autosomal dominant pattern.
5. **Time the splenectomy:** Splenectomy is considered once the child is older and the anaemia is significant, after vaccination and with penicillin cover thereafter.
6. **Consider the contrast:** A normal MCHC, no spherocytes and normal osmotic fragility make pyruvate kinase deficiency more likely, with a normal EMA test. In India, G6PD deficiency and thalassaemia are far more frequently encountered causes of haemolysis, so the membrane defect is considered after those are reviewed.

## Where the examiner sets the trap

Hereditary spherocytosis questions tend to turn on a few decision points.

- **Trap:** Applying osmotic fragility without a Coombs test. — **Correct:** Autoimmune haemolytic anaemia also produces spherocytes and raised fragility, so the direct Coombs test must be negative first.
- **Trap:** Treating the osmotic fragility result as definitive. — **Correct:** The EMA binding test is more reliable, especially in mild or borderline cases.
- **Trap:** Ignoring the raised MCHC as a clue. — **Correct:** Most other anaemias do not produce a raised MCHC, so it points towards spherocytosis.
- **Trap:** Forgetting the post-splenectomy risk. — **Correct:** Encapsulated organisms are the concern, so vaccines are given before surgery and lifelong penicillin prophylaxis follows.

## Frequently asked questions

### What does the EMA binding test measure in hereditary spherocytosis?

The eosin-5-maleimide binding test measures binding to band 3 and related membrane proteins by flow cytometry, and reduced binding supports hereditary spherocytosis. It is more sensitive and specific than osmotic fragility testing and is particularly useful when results are borderline.

### Why is a Coombs test performed in a patient with suspected spherocytosis?

A negative direct antiglobulin test excludes autoimmune haemolytic anaemia, which also produces spherocytes and increased osmotic fragility. A positive result points to autoimmune haemolysis instead, and the management changes accordingly.

### When is splenectomy indicated in hereditary spherocytosis?

Splenectomy is considered for significant symptomatic anaemia, growth problems or complications such as gallstones, and it is typically deferred until after early childhood. Patients need pneumococcal, meningococcal and Haemophilus influenzae type b vaccination before surgery and lifelong penicillin prophylaxis afterwards.

### How does pyruvate kinase deficiency differ from hereditary spherocytosis?

Pyruvate kinase deficiency is an enzyme defect with normal osmotic fragility and no spherocytes, whereas hereditary spherocytosis is a membrane defect with increased fragility and spherical cells. The EMA binding test is normal in pyruvate kinase deficiency, which is the key contrast.