[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/) › Sickle cell disease

# Sickle cell disease

- Lesion

One amino acid change makes haemoglobin stack into rods when oxygen is low. Stiff sickled cells block small vessels and break early.

Updated Nov 12, 2026

## Key points

- Sickling increases with low oxygen, acidosis, dehydration and high HbS concentration (high MCHC); HbF and HbA inhibit polymerization.
- Symptoms start after about six months of age as HbF falls.
- Vaso-occlusive crises: bone pain, acute chest syndrome, stroke, priapism, retinopathy, renal papillary necrosis.
- Spleen: congested and enlarged in childhood, then autosplenectomy; risk of sepsis by encapsulated bacteria and Salmonella osteomyelitis.
- Aplastic crisis (parvovirus B19) and splenic sequestration crisis in children.

On this page

- The basics Key points
- What it is
- Structure
- Step by step
- Markers
- Memory aid
- Elsewhere in DurgiPedia

- Clinical Clinical notes
- In the lab

- Study Test yourself

- Connections Connections

## What it is

Sickle cell disease is an autosomal recessive haemoglobinopathy caused by a point mutation that replaces glutamate with valine at position six of β-globin. Deoxygenated HbS polymerizes into long fibres, distorting and stiffening the red cell. Repeated sickling damages the membrane and dehydrates cells, producing chronic haemolysis, while sticky cells, inflammation and nitric oxide depletion cause microvascular occlusion and ischaemic injury in almost every organ. Trait confers protection against falciparum malaria, which explains its frequency in people of African descent, including Afro-Colombian communities.

## Structure

- Smear: irreversibly sickled cells, target cells and Howell–Jolly bodies.
- Marrow hyperplasia expands bones: crew-cut skull on radiographs, prominent cheekbones.
- Spleen: early congestion, thrombosis and infarcts; later a small fibrotic nubbin with haemosiderin (autosplenectomy).
- Infarcts and necrosis in bone, brain, kidney medulla, retina, lung and skin (leg ulcers).

## Step by step

- Valine replaces glutamate on β-globin, creating a hydrophobic patch.
- When deoxygenated, HbS molecules bind each other and form long polymer fibres.
- Cells take a sickle shape; repeated cycles damage the membrane and dehydrate the cell.
- Irreversibly sickled, rigid cells are removed by macrophages: chronic extravascular haemolysis.
- Sticky cells adhere to activated endothelium and leukocytes; free haemoglobin consumes nitric oxide.
- Slow flow in microvessels lets more cells sickle: occlusion, ischaemia and infarction.

## Markers

- HbS
- HbF level
- Irreversibly sickled cells

## Clinical notes

- Hand-foot syndrome (dactylitis) is often the first sign in infants.
- Acute chest syndrome (fever, chest pain, cough, infiltrates) and stroke are leading causes of death.
- Hydroxyurea raises HbF and reduces crises; vaccination and early antibiotics prevent many deaths.

## In the lab

- Haemoglobin electrophoresis or chromatography shows HbS; newborn screening detects it early.
- Trait carriers have about 40% HbS and are usually asymptomatic, except for renal concentrating defects.

## Memory aid

Glu to Val, low oxygen and the rods line up: the cell bends, the vessel blocks, the spleen dies first.

## Test yourself

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

## Why do infants with sickle cell disease have no symptoms in the first months?

Their red cells contain mostly fetal haemoglobin, which inhibits HbS polymerization; symptoms start as HbF falls.

## What is autosplenectomy?

Progressive infarction and fibrosis of the spleen in sickle cell disease, leaving a small fibrotic remnant and functional asplenia.

## Which factors favour sickling?

Low oxygen tension, acidosis, dehydration (higher HbS concentration) and slow transit through microvessels.

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## Elsewhere in DurgiPedia

- [Hemoglobin variants (HbA, HbA2, HbF, HbS, HbC)](https://durgical.com/en/biochemistry/topics/hemoglobin-variants/)
- [Hemoglobin and 2,3-BPG](https://durgical.com/en/biochemistry/enzymes/hemoglobin-and-2-3-bpg/)
- [Sickle cell disease and the eye](https://durgical.com/en/ophthalmology/sickle-cell-disease-and-the-eye/)

## Connections

## Related 5

- [Infarction: red vs white, and what decides the damage](https://durgical.com/en/general-pathology/infarction-red-vs-white-and-what-decides-the-damage/)
- [Other lesions of the spleen](https://durgical.com/en/general-pathology/other-lesions-of-the-spleen/)
- [Haemolysis: extravascular vs intravascular](https://durgical.com/en/general-pathology/haemolysis-extravascular-vs-intravascular/)
- [Thalassaemias: β and α](https://durgical.com/en/general-pathology/thalassaemias-and/)
- [Mendelian inheritance: autosomal dominant, recessive and X-linked](https://durgical.com/en/general-pathology/mendelian-inheritance-autosomal-dominant-recessive-and-x-linked/)

## Related conditions 7

- [Sickle cell disease](https://durgical.com/en/conditions/sickle-cell-disease/)
- [Priapism](https://durgical.com/en/conditions/priapism/)
- [Avascular necrosis of the femoral head](https://durgical.com/en/conditions/avascular-necrosis-of-the-femoral-head/)
- [Ischaemic stroke](https://durgical.com/en/conditions/ischaemic-stroke/)
- [Osteomyelitis](https://durgical.com/en/conditions/osteomyelitis/)
- [Asplenia and hyposplenism](https://durgical.com/en/conditions/asplenia-and-hyposplenism/)
- [Gallstones (cholelithiasis)](https://durgical.com/en/conditions/gallstones/)

## Microorganisms 2

- [Parvovirus B19](https://durgical.com/en/microbiology/parvovirus-b19/)
- [Plasmodium falciparum](https://durgical.com/en/microbiology/plasmodium-falciparum/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

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: [Sickle cell disease: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000527.htm) (MedlinePlus, US National Library of Medicine, 2026); [Sickle cell disease: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/sickle-cell-disease/) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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