Sickle cell anemia and sickle cell disease are disorders of hemoglobin in red blood cells that cause widespread tissue damage by leading to thrombosis (clotting) of primarily small blood vessels throughout the body. As a result of mutations in the hemoglobin beta chain gene under certain circumstances (dehydration, low oxygen environments, temperature extremes, etc) result in deformation of the red blood cells resulting in clumping and clotting (thrombosis). The deformed cells assume a sickle shape and they become more rigid.
The signs and symptoms can affect any organ or tissue. The primary symptom is intermittent pain which can be excruciating and debilitating. As a result of the small clots in blood vessels there is a lack of oxygenation of tissues downstream and cell death occurs. The spleen especially becomes scarred and dysfunctional in early childhood which compromises the immune system increasing the risk of recurrent infection such as sepsis, lung infections, and meningitis. In adults the primary causes of death in adults are secondary to pulmonary hypertension, brain strokes, and heart disease. The abnormal red blood cells break down and lead to anemia.
The eye, especially the retina, may suffer from lack of oxygen which leads to retinal damage and loss of vision. As a result, the eye attempts to form new capillaries which unfortunately bleed easily and cause scarring. In more advanced cases the retina may become detached.
This is an autosomal recessive condition which requires that both members of a pair of hemoglobin genes contain an alteration (mutation). The specific change varies but the alteration in one beta chain must create S hemoglobin while the other may also be an S chain (sickle cell anemia) or become a C or some other abnormal hemoglobin molecule (sickle cell disease). Frequently the sickling condition results in a child when one parent contributes the sickle gene and the other provides another sickle gene or a different abnormal hemoglobin. Such parents confer a 25% risk of sickle disease to each child.
The diagnosis of sickle disease is usually made at birth since this is evaluated as part of mandatory newborn screening. The diagnosis should be confirmed by gene testing within 6 months of birth. Lifelong monitoring is required due to the progressive and widespread nature of this disease. Infections must be treated promptly and the retinal disease can be treated with a variety of treatments designed to prevent bleeding.
Patients with the abnormal hemoglobin in their red blood cells should avoid extremes of temperature, strenuous exercise, dehydration, and low oxygen environments. The drug hydroxyurea may be beneficial for chronic pain management although it has little benefit in episodes of sickling crisis.
Longevity is reduced and death from complications such as infections may occur at any time. The median survival age range for adults with sickle cell disease is considered to be 42 to 50 years. The major cause of death in adults is cardiovascular disease.