A Serious Complication of Sickle Cell Disease in Children: Stroke

Sickle cell anemia is a dangerous, lifelong condition in which red blood cells can become sickle-shaped (like the letter "C"), unlike normal red blood cells, which are smooth and round.

Sickle cells are stiff and sticky, and tend to form clumps and get stuck in blood vessels, thereby blocking blood flow to the limbs and organs and causing pain, serious infections, and organ damage.

Approximately 80,000 people in the US have sickle cell disease, which, in this country, is most prevalent among African-Americans.

Sickle cell anemia is a genetic condition caused by a mutation in the normal (A) gene for hemoglobin - the red protein in blood that carries oxygen to the tissues. People who have the disease inherit two copies of the sickle (S) cell gene, one from each parent. Those who inherit a sickle cell gene from only one parent but have a normal gene from the other parent have a condition called sickle cell trait (AS). People with sickle cell trait are not ill and don't have the disease, but can pass the gene on when they have children.

Stroke
One of the most serious complications of sickle cell disease is stroke, caused when sickle-shaped cells block the tiny blood vessels in the brain. This type of stroke occurs mainly in children.

"About 20% of children with sickle cell disease (SCD) will have some form of stroke by the time they are teenagers," says John Paul Scott, MD, Medical College of Wisconsin Professor of Pediatrics and a specialist in blood disorders.

"Some will have a blockage in a large blood vessel supplying blood to the brain and this causes findings similar to what people think of in the elderly, with symptoms including paralysis on one side of the body and difficulty speaking or controlling facial muscles. Another 10-20% of patients will have had small areas of the brain that have been injured severely enough that we'll see it on a brain scan," explains Dr. Scott, who practices at the Children's Hospital of Wisconsin Hematology/Oncology Clinic.

"Injuries to the brain, such as stroke, may result in a loss of strength and coordination, but also cause a lower IQ in comparison to the child's peer group, causing learning disabilities and other problems," Dr. Scott explains.

Additional Complications
The signs and symptoms of sickle cell anemia are different in each person. Some people have fewer symptoms, but others have very frequent severe symptoms and are often hospitalized for treatment.

"There are some fairly characteristic problems that predominate at different stages of life and it's not known why certain things occur more frequently in one window of time versus another," says Dr. Scott. In addition to strokes, symptoms and complications of SCD include:

• anemia-related fatigue, paleness, shortness of breath
• sudden episodes of pain throughout the body
• infections
• acute chest syndrome (similar to pneumonia)
• delayed growth
• eye problems
• pulmonary arterial hypertension (high blood pressure)
• multiple organ failure

"The most distressing aspect of it is that we still don't have good tools to predict which child is going to have more trouble than others, although I think answers are forthcoming. There are a lot of genetic studies being done to identify who is most likely to be targeted for bad problems," says Dr. Scott.

Sickle Cell Center at Children's Hospital
Dr. Scott notes that Milwaukee is fortunate to have access to exceptional sickle cell treatment at the Children's Hospital of Wisconsin Sickle Cell Center, where teams of healthcare professionals are dedicated to helping families deal with the disease.

Screening and Diagnosis
Sickle cell disease is diagnosed with a simple blood test. Early diagnosis is vital so that children who have the condition can get proper treatment. SCD is most often diagnosed at birth during routine newborn screening tests, which are done on infants in most States.

"Newborn screening program for sickle cell has been done in Wisconsin since 1988," says Dr. Scott. "We know the identity of every child with sickle cell disease born in the state since November 1, 1988."

SCD can also be diagnosed before birth using amniocentesis, which uses a sample of amniotic fluid or tissue taken from the placenta to identify the sickle cell gene.

For many years the treatment of sickle cell disease was limited to symptomatic treatment like pain medications and blood transfusions to control complications (pain, acute chest syndrome) of the disease. One licensed drug, Hydroxyurea, has been shown to reduce the amount of pain and other complications by about half.

About 200 patients in the world have been cured of SCD by stem cell transplantation but at the current time only a small number of patients qualify for transplant because they do not have a perfectly matched donor. As for all chronic illnesses, regular medical checkups and expert treatment by a team of nurses, social workers, genetic counselors and physicians is critically important.

Dr. Scott explains that although sickle cell disease can be identified and symptoms treated, other problems can't be predicted. "There is clearly a difference in our genetic makeup that affects outcomes. If we can determine which genes have a higher predictive value for strokes and other complications, those patients could be targeted for intervention early in their lives."

John Paul Scott, MD, practices at the Children's Hospital of Wisconsin Cancer and Blood Disorders Center.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.