Treating Sickle Cell Disease

While there is not yet a viable, widely available cure for SCD, there are ways to help prevent and treat symptoms and complications. These include:

This section includes information on:

• Vaccinations
• Ongoing monitoring
• Drug therapies
• Fluid therapy
• Blood transfusions
• Surgery
• Bone marrow/stem cell transplantation
• Emerging therapies and promising research

Vaccinations

Vaccination against pneumonia should start at six months of age to help protect children from Streptococcus pneumoniae bacteria. In addition to the routine childhood immunizations, which all children with SCD should receive, SCD patients of all ages should receive an annual flu vaccination.

Ongoing monitoring

SCD patients require regular testing and monitoring to:

• Assess the severity of anemia and determine whether red blood cells are being produced appropriately (patients of all ages)

• Evaluate liver and kidney function (patients of all ages)

• Assess heart and lung function and check for the presence of pulmonary hypertension (adolescents and adults)

• Measure iron level—often high because of frequent blood transfusions—to determine if therapy is necessary to lower it before it reaches a toxic level

Another test uses transcranial Doppler imaging to identify children with SCD who are at high risk for suffering a stroke. Because up to 10 percent of pediatric SCD patients do suffer strokes, TCD screening, which is painless, is recommended for all children 2 to 16 years old who have SCD. Strokes can be prevented with regular prophylactic transfusions.

Drug therapies

In addition to medications prescribed to combat the pain of vaso-occlusive events, SCD patients may be prescribed drugs that include:

• Hydroxyurea. Originally an antitumor drug, HU was the first compound proven to successfully treat adults experiencing many of the serious complications associated with SCD.

HU works by promoting the body's production of the type of hemoglobin typically produced by fetuses (HbF), which has been shown to prevent the sickling of red blood cells.

Droxia, the brand-name form of HU, was approved by the Food and Drug Administration for use in SCD patients in 1998, and it is now a commonly prescribed drug therapy that is available in a generic form. It has been shown to reduce the incidence of vaso-occlusive episodes and acute chest syndrome and to prolong life expectancy. More recent studies also have suggested that it is effective and safe in children. However, it is contraindicated for both men and women who want to conceive a child, because of its possible adverse effects on the fetus.

While people who take HU for sickle cell disease require frequent blood count monitoring, they generally experience less severe anemia and fewer vaso-occlusive episodes—and therefore require fewer blood transfusions—than they did prior to therapy.

• Antibiotics. Babies born with SCD are at high risk for developing infections that can become life-threatening within hours, particularly bacterial pneumonia caused by Streptococcus pneumoniae. For this reason, children should be given oral penicillin starting at 2 months of age until they are at least 5 years old. Other drugs, including erythromycin, can be used for children with a known or suspected penicillin allergy.

The use of prophylactic antibiotics is not generally recommended for older children and adults, except as individual circumstances warrant.

• Folic acid. The high rate of red blood cell production in SCD patients requires copious amounts of folic acid, a vitamin plentiful in fresh green vegetables. Many physicians prescribe a folic acid supplement to patients with SCD.

Fluid therapy

Because people with sickle cell disease lose water their body needs in their urine, they can easily become dehydrated. Dehydration results in higher whole-blood viscosity ("thicker" blood) and therefore decreased circulation through small blood vessels. For this reason, patients are always encouraged to drink plenty of fluids. When they are ill and cannot keep up with their fluid needs, intravenous fluids are commonly recommended.

Blood transfusions

Blood transfusions are frequently indicated for SCD patients who experience severe complications, such as stroke or acute chest syndrome, or who become severely anemic. The transfusions serve several purposes, including:

• Replenishing the body's reserve of red blood cells
• Lowering the risk of stroke, or even reversing a blockage that has caused a stroke
• Replacing blood trapped in the spleen
• Reversing the process that leads to acute chest syndrome

Because frequent transfusion can lead to toxic, organ-damaging levels of iron in the bloodstream, patients should have their blood-iron levels monitored regularly.

Surgery

SCD patients often must undergo surgery for complications of their disease.

Children may require a splenectomy if they suffer from repeated or particularly severe splenic sequestration crises. Older children and young adults often need their gallbladders removed because of the accumulation of gallstones that contain hemoglobin byproducts. Young adult and middle-aged patients who suffer from avascular necrosis and osteonecrosis may benefit from joint replacement surgery, such as for their hips and knees.

Bone marrow/stem cell transplantation

The only currently available cure for SCD is bone marrow/stem cell transplantation. This is a very risky procedure—approximately 5 percent of patients do not survive—and it is used only in very severely affected children and young adults for whom there is a donor who is an appropriate genetic match. Most often, these donors are siblings who do not have SCD, but with the increasing availability of cord blood, some patients now undergo transplantation with cord blood-derived stem cells.

Of the 200-plus children with SCD who have undergone bone marrow/stem cell transplantation, approximately 85 percent appear to have been cured. In other cases, the transplant failed but the patient's own bone marrow recovered from the chemotherapy—meaning that the patient survived but still had sickle cell disease.

Emerging therapies and promising research

Scientists are currently investigating a number of ways to treat SCD more effectively:

• Gene therapy. Genetic therapy—giving the patient a "good" copy of the gene to replace the faulty gene—potentially could offer a cure without the risks of bone marrow/stem cell transplantation.
• Nitric oxide. This gas reduces inflammation and causes the blood vessels to expand.
• Decitabine and butyrate. These compounds, like hydroxyurea, promote the body's production of fetal hemoglobin, which prevents the sickling of red blood cells

Researchers at Duke Medicine and elsewhere continue to conduct animal studies and clinical trials into issues such as:

• Genetic factors that influence the severity and specific complications of SCD, which can vary greatly among patients
• The structure of the red blood-cell membrane: how it is affected by SCD and how it causes the cells to become sticky and get stuck in blood vessels
• Ways to deliver normal hemoglobin genes into the stem cells that give rise to red blood cells
• The potential of nitric oxide to reduce or reverse vaso-occlusion, acute chest syndrome, and pulmonary hypertension
• The effects of sickled red blood cells on other tissues
• Pulmonary hypertension in people with SCD
• The use of hydroxyurea in preventing strokes in children at high risk