Sickle Cell Disease: Symptoms, Causes & Treatment

Sickle cell disease is an inherited condition passed from parents to children that causes red blood cells to become rigid and shaped like a sickle. This abnormal shape makes it harder for the cells to carry oxygen throughout the body.

Because of this, oxygen delivery to tissues is reduced, which can lead to symptoms such as fatigue and pale skin. The altered shape of the cells also increases the risk of blood vessel blockages.

These blockages can trigger pain episodes and other complications that affect different parts of the body. Management is typically guided by a hematologist and may include medications, blood transfusions, or advanced therapies.

Sickle cell disease symptoms

The main symptoms of sickle cell disease include:

• Pale skin, lips, and nails

• Swelling, pain, and redness in the hands and feet

• Leg ulcers

• Severe fatigue

• Frequent infections

• Shortness of breath or dizziness

• Irritability or difficulty concentrating

A very common symptom is severe pain that can affect the whole body, but it most often occurs in the bones and joints, abdomen, chest, and lower back.

These pain episodes, known as crises, can vary in intensity and may last from a few hours to several days, or become chronic.

Other possible symptoms include yellowing of the skin and eyes (jaundice), delayed growth and puberty, and vision problems.

Symptoms usually begin around 6 months of age.

Confirming a diagnosis

Sickle cell disease is typically diagnosed in the first days of life through routine newborn screening performed by a neonatologist or pediatrician.

To confirm the diagnosis, additional tests such as hemoglobin electrophoresis or blood bilirubin levels may be ordered.

Once confirmed, the person is referred to a hematologist for ongoing care and management.

What causes sickle cell disease?

Sickle cell disease is a genetic condition passed from parents to children.

It is caused by a mutation in the gene responsible for producing the beta subunit of hemoglobin, the protein in red blood cells that carries oxygen to body tissues.

As a result of this mutation, red blood cells become sickle-shaped, which interferes with normal blood flow and oxygen delivery.

Is sickle cell disease cancer?

Sickle cell disease is not cancer.

It is caused by inherited genetic changes that affect the shape of red blood cells, whereas cancer develops when cells grow and divide uncontrollably due to DNA mutations.

Sickle cell disease treatments

Treatment for sickle cell disease is guided by a hematologist and focuses on relieving symptoms and preventing complications.

The main treatment options include:

1. Medications

Medications are used to manage pain and reduce the frequency of complications.

The most common medications include:

• Pain relievers or nonsteroidal anti-inflammatory drugs (NSAIDs), such as acetaminophen, for mild to moderate pain

• Opioids, such as morphine, for severe pain

• Hydroxyurea or L-glutamine, to reduce the frequency of pain crises

• Crizanlizumab, which helps reduce pain crises in adults and adolescents aged 16 and older

To help prevent infections, it is also important to keep vaccinations up to date.

According to NHLBI clinical practice guidelines and CDC recommendations, preventive oral penicillin is recommended until age 5 to reduce the risk of invasive pneumococcal infection in children with HbSS.

2. Blood transfusion

Blood transfusions may be recommended to prevent serious complications such as stroke or sudden worsening of anemia caused by infections or an enlarged spleen.

This treatment involves transfusing packed red blood cells to restore healthy oxygen transport throughout the body.

To prevent iron overload from repeated transfusions, iron chelation therapy may be prescribed, including medications such as deferasirox, deferoxamine, or deferiprone.

In children, stroke risk screening is also an important part of care. According to CDC and American Society of Hematology recommendations, children and adolescents ages 2 to 16 years with sickle cell anemia should have yearly transcranial Doppler ultrasound tests to check for an increased risk of stroke.

3. Erythrocytapheresis

Erythrocytapheresis may be recommended for people who require frequent transfusions.

This procedure uses a machine to remove abnormal red blood cells and replace them with healthy donor cells, helping extend the time between transfusions.

4. Hospitalization

Hospitalization may be necessary during severe pain crises.

Treatment typically includes intravenous (IV) fluids, pain medications, and oxygen therapy if oxygen levels fall below 95%. IV antibiotics may also be used to prevent or treat infections.

Acute chest syndrome requires urgent medical attention. The CDC describes acute chest syndrome as a life-threatening complication and a medical emergency that should be treated in the hospital right away.

5. Surgery

Surgery may be recommended in cases of severe or recurrent splenic sequestration.

This condition occurs when sickled cells block blood vessels in the spleen, causing blood to become trapped and potentially leading to life-threatening complications.

The procedure, called a splenectomy, involves removing the spleen and is usually performed laparoscopically with a relatively quick recovery.

6. Bone marrow transplant

Bone marrow transplant, also known as allogeneic hematopoietic stem cell transplantation, may offer a potential cure in some cases.

In this procedure, healthy bone marrow from a compatible donor is transplanted to restore normal red blood cell production.

7. Gene therapy

Gene therapy is an emerging treatment option for sickle cell disease using exagamglogene autotemcel (Casgevy).

This therapy modifies the patient’s own cells using CRISPR/Cas9 technology and reinfuses them to increase fetal hemoglobin production, helping prevent red blood cells from becoming sickle-shaped.

Is there a cure?

Most treatments for sickle cell disease focus on symptom control and preventing complications rather than providing a cure.

However, a cure may be possible in select cases through hematopoietic stem cell transplantation.

This option is typically reserved for severe cases due to potential risks.

Life expectancy

Life expectancy varies depending on disease severity and the presence of complications.

With advances in treatment, survival has improved, although the condition can still reduce life expectancy.

Possible complications

Sickle cell disease can lead to both acute and chronic complications, including:

• Acute chest syndrome or splenic sequestration crises

• Fat embolism, bone infarction, or necrosis

• Stroke, heart attack, or venous thrombosis

• Eye hemorrhage, retinal detachment, or blocked retinal blood vessels

• Delayed growth and development

• Heart, lung, or liver disease

Other possible long-term complications include chronic kidney disease and kidney failure, as well as endocrine problems such as hypogonadism and other hormone disturbances.