Sickle cell disease begins with sickling. 
Here's how it happens

In sickle cell disease, the body makes a type of hemoglobin called hemoglobin S (HbS). Hemoglobin is a protein in red blood cells that carries oxygen from the lungs and delivers it throughout the body.

Healthy hemoglobin

Healthy hemoglobin stays flexible whether it is carrying oxygen or not.

Illustration of a healthy red blood cell with hemoglobin labeled inside

Unhealthy hemoglobin

The genetic change in HbS causes the hemoglobin to link together.

Illustration of a sickled red blood cell with hemoglobin rods inside

The sickling process

Illustration of sickled hemoglobin rods
Unhealthy hemoglobin molecules link together

When red blood cells release oxygen, unhealthy hemoglobin molecules link together (polymerization), and form into stiff rods inside the cell.

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Image of a sickled red blood cell showing hemoglobin rods inside
Red blood cells change shape

These rods bend red blood cells into a sickle shape.

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Image of a cycle of sickling and unsickling of red blood cell
Red blood cells sickle and unsickle in a cycle

As red blood cells release and pick up oxygen, they repeatedly sickle and unsickle until they become permanently sickled over time.

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Image of a sickled red blood cell hemolyzing or breaking down
Red blood cells become fragile and break down (hemolysis)

Fragile red blood cells cannot withstand the stress of repeated sickling and unsickling and break down.

Repeated sickling and unsickling puts ongoing stress on red blood cells. This leads to red blood cells breaking down early.

Why don't red blood cells live as long (hemolysis) in 
sickle cell disease?

Energy plays a key role in red blood cell health

  • Red blood cells make energy. This energy is called ATP (adenosine triphosphate). Energy from ATP helps red blood cells keep their shape and work the way they should
  • Red blood cells don’t work as well in people with sickle cell disease. That’s because they keep changing shape and can’t carry oxygen as well as healthy red blood cells
  • Sickling and unsickling puts stress on red blood cells. In sickle cell disease, red blood cells do not have the energy they need to work properly and survive
  • Because of this, red blood cells can break down early and don’t live as long
How long can red blood cells live in your body?
Comparison of healthy and sickled red blood cell lifespans, showing a healthy red blood cell lasting 120 days and a sickled red blood cell lasting 10-20 daysComparison of healthy and sickled red blood cell lifespans, showing a healthy red blood cell lasting 120 days and a sickled red blood cell lasting 10-20 days

With less energy (ATP) and more stress, red blood cells in sickle cell disease break down early. This is called hemolysis.

Images are for illustrative purposes only.