Aging Begins at 30

Despite Advances, Sickle-cell Disease Is Still Incurable

Sickle cell disease is an inherited anemia occurring primarily in persons of African descent and rarely in Mediterranean origin whites. The blood oxygen carrying protein is abnormal and is called hemoglobin S (HbS for sickle). Technically, a valine amino acid replaces glutamic acid on the beta hemoglobin chain. Normal hemoglobin is adult or Hb A. In active tissues with reduced oxygen, Hb S crystallizes into rods that aggregate and make cells look like crescent shaped harvesting sickles. These cells are less pliable, much more fragile, and easily destroyed causing anemia. In 1949 Dr. Linus Pauling found that HbS moves slowly in an electric field compared to HbA, demonstrating for the first time an abnormal protein causing disease.

Sickle cell anemia patients inherit abnormal HbS genes from both parents. If the gene is inherited from only one parent that person has sickle cell trait (carrier state) but is usually free of symptoms. If two carriers have a child there is a 1 in 4 chance that their child will have sickle cell disease, a 2 in 4 chance of sickle cell trait and a 1 in 4 chance that the child will have neither. In the United State, about 150 black children in 100,000 have sickle cell disease and one in 12 sickle cell trait. In Africa, sickle cell trait slightly increases malaria survival, which may have caused gene persistence.

At Hopkins Hospital, my research technician was the daughter of Dr. James Herrick who described the disease in 1910 in a Grenadan dental student. He demonstrated by blood smear oxygen reduction sickled cells. Dr. Pauling’s electrophoresis method is now diagnostic.

After age 6 months the sickle cell child may have chronic fatigue, headaches, shortness of breath on exertion, pallor, leg ulcers, jaundice, and failure to thrive. Fluid concentration and acidity at the kidney center can lead to painless bloody urination. Slow growth and chronic kidney disease can occur.

Severe life-threatening sickle cell crises occur because of blocked blood vessels. They are caused by infection "particularly pneumonia and parvovirus", cold weather, prolonged sweating, diarrhea, or vomiting. The patient suffers excruciating pains in the bones or joints, possibly blood in the urine, or lungs or intestine damage that will mimic gall bladder colic, appendicitis, or a perforated viscus. With nervous system involvement, seizures, stroke, or coma can occur.

Genetic counseling is important as there is a 25% disease risk if both parents are carriers. In the second pregnancy trimester abnormal amniotic fetal cells can be detected. If positive, parents may decide to interrupt the pregnancy. Vaccines to prevent infections are being studied.

A new treatment uses hydroxyurea, which stimulates the formation of a slightly different or fetal hemoglobin (HbF) that inhibits sickling. Treatment is otherwise supportive and conservative. There is no cure. Crises require intravenous fluids for dehydration, antibiotics for infection, oxygen to prevent sickling, and pain medicine. Rarely an exchange transfusion to temporarily replace Hb S helps. Anesthesia is hazardous as it stimulates sickling. Until about 1960 many sickle patients died in childhood. At present, life can be shortened rarely by as much as 20 years.

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See related Patient Topics Blood/Lymphatic System, Genetics/Birth Defects or Sickle Cell Anemia.

See related Provider Topics Blood/Lymphatic System, Genetics/Birth Defects or Sickle Cell Anemia.

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