Sickle Cell Disease (SCD)


Sickle cell disease (SCD) comprises a group of disorders in which mutations in the HBB gene1 cause an abnormal type of hemoglobin, called hemoglobin S, to form. As a result, the red blood cells (RBCs) assume a sickle or crescent shape. The sickled RBCs die prematurely, so that anemia develops. They are also inflexible and may be unable to pass through small blood vessels. Vascular obstruction leads to serious complications.2

Most newborns with SCD do not exhibit any symptoms until the age of 5 or 6 months because they are protected by high levels of fetal hemoglobin (HbF). However, the condition soon becomes evident once the HbF levels decrease.

The severity of symptoms varies from one individual to another and over time. Although some people have mild symptoms, others may experience serious complications that require hospitalization.3

Anemia

In SCD, the RBCs die within 10 to 20 days, whereas normal RBCs usually survive for 120 days. This rapid breakdown of sickle-shaped RBCs causes anemia. The consequences include shortness of breath, fatigue, reduced energy and endurance, and delayed growth and development in children.4

Jaundice

Because of the premature breakdown of sickled RBCs, levels of bilirubin, a yellow-colored protein, are increased, causing the eyes and skin to appear yellow, a condition called jaundice. If levels of bilirubin remain elevated for a long time, gallstones may form.5

Vaso-occlusive Crisis

Because sickle-shaped RBCs are stiff and inflexible, they are unable to pass through small blood vessels. Obstruction of the blood flow causes painful episodes termed vaso-occlusive crises. Recurrent episodes of vaso-occlusion result in oxygen deprivation and progressive damage to tissues and organs, including the brain, lungs, kidneys, bones, spleen, and cardiovascular system. Pain can occur in any part of the body but usually develops in the bones of the arms, legs, chest, and spine. The pain may be triggered by cold weather, illness, dehydration, stress, or physical exertion.5,6

The pain varies in intensity as well as frequency. Whereas some patients have 6 or more painful episodes in a year, others may have only a single episode in a year. Some patients experience chronic low-level pain.7

Acute Chest Syndrome

Acute chest syndrome is a life-threatening condition that occurs when sickle-shaped RBCs block the flow of oxygenated blood in the lungs, damaging lung tissue and causing symptoms such as fever, chest pain, and breathing difficulties.3,5

Frequent Infections

Because SCD affects the spleen, children with SCD are at higher risk for infections. These range from mild (eg, flu) to lethal (eg, meningitis and pneumonia). Therefore, it is recommended that Infants and children with SCD be vaccinated and given antibiotics to reduce the risk for infections.4,7

Splenic Sequestration

Sickle-shaped RBCs can block the flow of blood from the spleen. Painful splenic enlargement due to accumulation of RBCs in the sleep can be lethal if left untreated. Surgical removal of the spleen is required in cases of severe sequestration.8

Stroke

Sickle-shaped cells can block the major blood vessels that supply the brain with oxygen, resulting in significant brain damage. Symptoms of stroke can include weakness, slurred speech, vision changes, unexplained numbness, seizure, confusion, loss of coordination, dizziness, and severe headache.7

Other Symptoms

Blockage of blood flow due to sickled RBCs can damage the liver, heart, kidneys, gallbladder, eyes, bones, and joints, leading to problems including leg ulcers, bone or joint damage, pulmonary hypertension, kidney damage, and visual impairment.4

Pain and swelling of the hands and feet due to obstructed blood flow, a condition called dactylitis, often develops in children with SCD. Blockage of blood vessels in the penis by sickled RBCs results in priapism, which is a painful and prolonged erection.3

References

  1. HBB gene. MedlinePlus Genetics. Accessed November 23, 2021.
  2. Sickle cell disease. MedlinePlus Genetics. Accessed November 23, 2021.
  3. Sickle cell disease. NIH. National Heart, Lung, and Blood Institute. Updated September 1, 2020. Accessed November 23, 2021.
  4. Sickle cell disease—symptoms. NHS. Accessed November 23, 2021.
  5. Sickle cell disease (for teens). Hematology at Nemours Children’s Health. Reviewed July 2018. Accessed November 23, 2021.
  6. Yale SH, Nagib N, Guthrie T. Approach to the vaso-occlusive crisis in adults with sickle cell disease [published correction appears in Am Fam Physician 2001 Jul 15;64(2):220]. Am Fam Physician. 2000;61(5):1349-1364. PMID: 10735342.
  7. Sickle cell anemia. Mayo Clinic. Accessed November 23, 2021.
  8. Kane I, Nagalli S. Splenic sequestration crisis. StatPearls. Updated July 26, 2021. Accessed November 23, 2021.

Reviewed by Kyle Habet, MD, on 11/30/2021.

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