What Is Sickle Cell Anemia Caused By?

Sickle cell anemia is a chronic, inherited blood disease predominantly occurring in people of African descent. The red blood cells (RBCs) contain hemoglobin S (Hgb S) rather than the normal hemoglobin A (Hgb A). These cells are prone to malformation when physical stress reduces the oxygen content of the blood, as in illness, exertion and exposure to cold. Blockage of the small vessels by the sickled cells causes painful crises, trouble breathing and damage to organs.

Physiology

• "Sickle cell" refers to the characteristic shape of affected red blood cells (RBCs) in this disease. When the oxygen content of the blood is low, the shape of the RBCs changes from a biconcave disc to a sickle (or crescent) shape. These RBCs are inflexible and too fragile to pass through blood vessels without damage. The dead and damaged RBCs are broken down by the body, a process known as hemolysis, which results in low RBC counts.

Genetics

• Sickle cell anemia occurs in people who are homozygous for the disease--that is, they inherit the gene for sickle cell from both parents. People who inherit the gene from only one parent (heterozygous) are said to have sickle cell trait. The gene is so common in people of African descent that it is postulated that it may serve a function, perhaps as protection against malarial infection.

Vaso-occlusive Symptoms

• The inability of sickled RBCs to pass through small blood vessels causes blockage of those vessels. These vaso-occlusive events can result in loss of blood flow and permanent damage to tissues. Children with sickle cell disease will often suffer severe pains in the hands and feet. Long bone pain is common in sickle cell patients of all ages. Blockage of the kidney vessels can decrease renal efficiency. Priapism and impotence are common in males.

Respiratory Symptoms

• Blockage of the tiny vessels of the lungs leads to acute chest syndrome, with symptoms similar to bacterial pneumonia (including fever, chest pain, increased white blood cell counts, and infiltrates of the lung visible on chest X-ray). Ventilator support is necessary during these attacks. Acute chest syndrome commonly occurs after a respiratory infection.

Treatment and Prognosis

• Once unlikely to survive to adulthood, sickle cell patients now routinely live into their fifties. Treatment is symptomatic, and includes oxygen treatment in respiratory crises, analgesics for pain crises, and oral and intravenous hydration. Common causes of death include pulmonary emboli (blood clots in the lung), renal failure and blockage of a vessel leading to the heart, brain or another vital organ.

Sickle Cell Trait

• Patients with sickle cell trait experience a milder range of symptoms than those who are homozygous for the disease. They may be prone to short episodes of renal bleeding, which usually resolve on their own. They have a greater risk than the general population for sudden death after prolonged intensive exercise.

Testing

• Testing for sickle cell trait is available and can be performed on potential carriers. A blood sample is exposed to reduced-oxygen conditions. This will cause any affected cells to sickle. If this screening is positive, a series of blood tests are performed to identify the presence of Hgb S and the ratio of Hgb S to Hgb A (normal Hgb). Those with sickle cell anemia have very little Hgb A, while patients with sickle cell trait have more Hgb A than Hgb S. In most states, newborns are routinely screened for Hgb S.