Sickle cell anemia is a disease passed down through families in which red blood cells are an abnormal crescent shape. (Red blood cells are normally shaped like a disc.)

Sickle cell anemia is caused by an abnormal type of hemoglobin called hemoglobin S. Hemoglobin is a protein inside red blood cells that carries oxygen. Hemoglobin S, however, distorts the red blood cells' shape. The fragile, sickle-shaped cells deliver less oxygen to the body's tissues, and can break into pieces that disrupt blood flow.

Sickle cell anemia is inherited as an autosomal recessive trait. This means it occurs in someone who has inherited hemoglobin S from both parents. Sickle cell disease is much more common in certain ethnic groups, affecting approximately one out of every 500 African Americans. Someone who inherits hemoglobin S from one parent and normal hemoglobin (A) from the other parent will have sickle cell trait. Someone who inherits hemoglobin S from one parent and another type of abnormal hemoglobin from the other parent will have another form of sickle cell disease, such as thalassemia.

Although sickle cell disease is present at birth, symptoms usually don't occur until after 4 months of age. Sickle cell anemia may become life threatening. Blocked blood vessels and damaged organs can cause acute painful episodes, or "crises." There are several types of crises:

1. Hemolytic crisis occurs when damaged red blood cells break down
2. Splenic sequestration crisis is when the spleen enlarges and traps the blood cells
3. Aplastic crisis results when an infection causes the bone marrow to stop producing red blood cells

These painful crises, which occur in almost all patients at some point in their lives, can last hours to days, affecting the bones of the back, the long bones, and the chest. Some patients have one episode every few years, while others have many episodes per year. The crises can be severe enough to require admission to the hospital for pain control and intravenous fluids.

Repeated crises can cause damage to the kidneys, lungs, bones, eyes, and central nervous system.

Common symptoms include:

• Attacks of abdominal pain
• Bone pain
• Breathlessness
• Delayed growth and puberty
• Fatigue
• Fever
• Jaundice
• Paleness
• Rapid heart rate
• Susceptibility to infections
• Ulcers on the lower legs (in adolescents and adults)

The patient may also have:

• Bloody urine (hematuria)
• Chest pain
• Excessive thirst
• Frequent urination
• Painful erection (priapism; this occurs in 10 - 40% of men with the disease)
• Poor eyesight/blindness

Tests commonly performed to diagnose and monitor patients with sickle cell anemia include:

• Complete blood count (CBC)
• Hemoglobin electrophoresis
• Sickle cell test

Patients with sickle cell may have abnormal results on certain tests, as follows:

• Amount of oxygen in the blood may be decreased
• CT scan or MRI may show strokes in certain circumstances
• Elevated bilirubin
• High serum creatinine
• High serum potassium
• High white blood cell count
• Peripheral smear displays sickle cells
• Serum hemoglobin will be decreased
• Urinary casts or blood in the urine

Patients with sickle cell disease need continuous treatment, even when they are not having a painful crisis. Supplementation with folic acid, an essential element in producing red blood cells, is required because of the rapid red blood cell turnover.

The purpose of treatment is to manage and control symptoms, and to try to limit the frequency of crises.

During a sickle crisis, certain treatments may be necessary. Painful episodes are treated with analgesics and enough liquid intake. Treatment of pain is critical. Non-narcotic medications may be effective, but some patients will require narcotics.

Hydroxyurea (Hydrea) was found to help some patients by reducing the frequency of painful crises and episodes of acute chest syndrome (which includes chest pain and difficulty breathing). It also decreases the need for blood transfusions. There has been some concern about the possibility of this drug causing leukemia, but as yet there are no definitive data that Hydrea causes leukemia in sickle cell patients.

Newer drugs are being developed to manage sickle cell anemia. Some of these drugs work by trying to induce the body to produce more fetal hemoglobin (therefore decreasing the amount of sickling), or by increasing the binding of oxygen to sickle cells. As yet, there are no other widely used drugs that are available for treatment.

Bone marrow transplants can cure the disease, but it is only recommended in a minority of patients. This is mostly due to the high risk of the procedure (the drugs needed to make the transplant possible are highly toxic) and the difficulty in finding suitable donors. Also, bone marrow transplants are much more expensive than other treatments.

Antibiotics and vaccines are given to prevent bacteria infections, which are common in children with sickle cell disease.

Additional treatments may include:

• Dialysis or kidney transplant for kidney disease
• Drug rehabilitation and counseling for the psychological complications
• Gallbladder removal (if there is significant gallstone disease)
• Hip replacement for avascular necrosis of the hip (death of the joint)
• Irrigation or surgery for priapism (persistent, painful erections)
• Partial exchange transfusion for acute chest syndrome
• Surgery for eye problems
• Transfusions or surgery for brain problems, such as strokes
• Wound care, zinc oxide, or surgery for leg ulcers

Sickle cell anemia, like other chronic, life-threatening diseases, can cause great stress to the patient and family members. Joining a support group, where members share common experiences and problems, can relieve this stress. See sickle cell anemia - support group.

In the past, death from organ failure often occurred between the ages of 20 and 40 in most sickle-cell patients. More recently, because of better understanding and management of the disease, patients live into their forties and fifties.

Causes of death include organ failure and infection. Some people with the disease experience minor, brief, and infrequent episodes. Others experience severe, prolonged, and frequent episodes resulting in many complications.

• Acute chest syndrome
• Blindness / visual impairment
• Death
• Erectile dysfunction (as a result of priapism)
• Gallstones
• Infection, including pneumonia, cholecystitis (gallbladder), osteomyelitis (bone), and urinary tract infection
• Joint destruction
• Leg ulcers
• Loss of function of the spleen
• Multisystem disease (kidney, liver, lung)
• Narcotic abuse
• Neurologic (brain and nervous system) symptoms and stroke
• Parvovirus B19 infection resulting in aplastic crisis
• Recurrent aplastic and hemolytic crises resulting in anemia and gallstones
• Splenic sequestration syndrome
• Tissue death of the kidney

Call your health care provider if acute painful crises occur or at the first sign of any infection.

Sickle cell anemia can only result when two carriers with sickle cell trait have a child together. Therefore, genetic counseling is recommended for all carriers of sickle cell trait. About 1 in 12 African Americans has sickle cell trait. Diagnosis of sickle cell anemia during pregnancy is also available.

Prompt treatment of infections, adequate oxygenation, and preventing dehydration may prevent sickling of red blood cells. Antibiotics and vaccinations may prevent infections.

General health visits with a physician are recommended to ensure the patient is getting adequate nutrition, maintains proper activity levels, and receives proper vaccinations.

PREVENTING CRISES

Parents whose children have sickle cell disease should encourage their children to lead normal lives. However, in order to decrease the occurrence of sickle cell crises, consider the following precautions:

To prevent loss of oxygen from tissues, avoid the following:

1. Demanding physical activity, especially if the spleen is enlarged
2. Emotional stress
3. Environments with low oxygen content (high altitudes, non-pressurized airplane flights)
4. Known sources of infection

To promote proper hydration:

1. Recognize signs of dehydration
2. Avoid too much exposure to the sun
3. Provide access to fluids, both at home and away

To avoid sources of infection:

1. Keep child properly immunized as recommended by the health care provider
2. Consider having the child wear a Medic Alert Bracelet
3. Share above information with teachers and other caretakers as appropriate

Be aware of the effects that chronic, life-threatening illnesses can have on siblings, marital relationships, parents, and the child.

Goldman L, Ausiello D. Cecil Textbook of Medicine. 22nd ed. Philadelphia, Pa: WB Saunders; 2004:1030-1039

Hoffman R, Benz Jr. EJ, Shattil SJ, et al., eds. Hematology: Basic Principles and Practice. 4th ed. Philladelphia, Pa: Churchill Livingston; 2005:591-634.