Sickle Cell Disease:

The Who, What and Why

Although sickle cell disease primarily affects African-Americans, individuals of other ethnic backgrounds may also be affected. Approximately 1 in 375 African-American children has sickle cell disease. Other ethnic groups affected include Hispanic Americans from the Caribbean, South America and Central America, as well as individuals from Greece, Italy, Turkey, the Middle East, and East India. So what exactly is sickle cell disease

History of Sickle Cell Disease

1910 Herrick described sickled cells in the blood of a dental student. The term sickle cell anemia was used because of the “sickled” shape of the blood cell.

1930 Seriver and Waugh showed that sickled cells were present in the red cells of 7-10 percent of African Americans.

1934 Diggs and Ching reported that occlusion of the blood vessels might be responsible for the painful “crises” of sickle cell disease (SCD).

1949 Neel and Beet described how SCD is inherited.

1950 Itano and Neel reported a mild form of SCD that was a mixture of two hemoglobins: hemoglobin S and hemoglobin C.

1951 Neel reported another mild form of SCD that was a mixture of hemoglobin S and thalassemia.

1957 Ingram demonstrated that the abnormality of Hemoglobin S is a substitution in the amino acid chain.

1970 Ali found a mild form of SCD in Saudi Arabia associated with a higher fetal hemoglobin.

1973 Garrick developed a test to screen newborns for SCD.

1974 Pearson discussed the importance of testing all newborns for SCD.

1974 Kan and associates developed a test for prenatal diagnosis by testing fetal blood from the umbilical cord.

1984 Nagel, Wainscoat, Labie, Kazazian and Orkin discovered 3 major genetic DNA types of SCD. They are termed Benin, Senegal, and the Central African Republic after the areas in which they are common in Africa.

1987 A panel recommended that all infants born in the U.S. be screened at birth for SCD and that affected infants be placed on prophylactic penicillin by the age of three months.

1991 The Pediatric Sickle Cell Center at Long Beach Memorial Medical Center was approved by California Children’s Services (CCS).

1993 The Pediatric Sickle Cell Center at Long Beach Memorial Medical Center started using the TCD annually to screen for stroke risk in all children with SCD.

1995 The SCD CCS Stroke Clinic was started at Long Beach Memorial Medical Center.

Sickle Cell Research

1978 The Cooperative Study of SCD (CSSCD) studied over 4,000 individuals including newborns to adults in their fifties throughout the U.S. to examine the clinical course of SCD.

1984 Hydroxyurea was shown to increase the fetal hemoglobin by Veith, Platt, Charuche, and Dover.

1986 Gaston and the CSSCD Penicillin Study demonstrated that infants and young children placed on prophylactic penicillin had lower rates of pneumoccal infection. This study provided the first preventive therapy for children with SCD which resulted in a significant reduction of the major cause of death of children between the ages of one and five.

1991 Platt and the CSSSD reported that the morbidity in SCD is related to the rate of pain crises.

1992 Charuche and co-workers completed the phase 1 study of hydroxyurea as a treatment for SCD.

1994 Platt and the CSSCD reported on the mortality and life expectancy associated with SCD. This study involved the participants with the entire spectrum of all DNA types of SCD.

1995 The Multicenter Study of Hydroxyurea demonstrated the first effective therapy for severely affected adult patients with SCD. There was a 50 percent reduction in pain crisis in patients with severe SCD.

1995 The Multicenter Study of Acute Chest Syndrome (ACS) was designed to determine the cause of ACS and the effectiveness of different treatments.

The Pediatric Sickle Center at Long Beach Memorial received an award for enrolling a large number of patients.

1996 Paula Groncy, M.D., Teddi Softley, Ph.D. and colleagues received a grant from the Long Beach Memorial Foundation for a study “Identification of Stroke Risk in Children with Sickle Cell Disease Through Multimodal Imaging”. Since the study opened, no children followed at our center have presented with overt clinical stroke.

1996 The first multicenter study of bone marrow transplantation in children with SCD reports that this procedure can provide a cure for young patients who have a matched sibling.

1996 Joetta DeSwarte-Wallace and colleagues conducted a national survey on the utilization of Desferal for iron chelation.

1997 The first SCD cell patient from Long Beach Memorial underwent a bone marrow transplant at the University of California at San Francisco Medical Center.

1997 Adams and the CSSCD STOP Stroke Study recommended that all children with SCD be screened every six months with TCD. Transfusion therapy was recommended for all children with average TCD velocities greater than 200.

1997 The Pediatric Sickle Cell Center co-sponsored its first National Conference with the Sickle Cell Disease Research Foundation. Two hundred people attended.

1997 Paula Groncy, M.D., Teddi Softley, Ph.D. and colleagues received a grant from the Long Beach Memorial Foundation for a follow-up study, “Progression of Cerebrovasculopathy in Children with Sickle Cell Disease”.

1998 The Multicenter Hip Coring Study opened for enrollment. The Pediatric Sickle Cell Center will participate in the National Study.

Complications

Persons with Sickle Cell Disease are at risk for a variety of complications including pain crises, infections, acute chest syndrome, stroke, splenic sequestration (spleen fills with blood), gallstones, leg ulcers, avascular necrosis (damage to the bones), kidney dysfunction, and priapism (persistent, unwanted erection of the penis).

We are fortunate to have a well-established Sickle Cell Center headed by Dr. Paula Groncy, M.D. The Sickle Cell Center at Miller Children’s at Long Beach Memorial Medical Center was established and approved by the state of California prior to 1993 as a clinic for patients insured by the California Children’s Services (CCS). CCS authorizes healthcare facilities and specialists to provide interdisciplinary services to children and adolescents with CCS insurance coverage. Patients at the Sickle Cell center are seen by a multi-disciplinary team composed of pediatric specialists including the hematologist/oncologist, neurologist, rehabilitation specialist, dentist, clinical nurse specialist, nutritionist, psychologist, social worker, and physical therapist. Generally, patients are seen at least semi-annually in this clinic for comprehensive sickle cell care with the primary focus being health promotion and prevention of complications. Numerous tests are recommended to screen for various problems or complications.

Listed below are many of the tests, frequency, and rationale of the tests ordered.

Audiogram: A hearing test important for diagnosis of hearing problems and for patients on a chronic transfusion program receiving Desferal since long-term use can cause hearing loss. Testing is recommended every 2 years after age five, or yearly for patients on a chronic transfusion program.

Opthamology Exam: An eye exam is recommended every 3 years after the age of 5, or sooner if indicated. Sickle Cell patients are at a high risk of changes or damage to the vessels of the eye due to blood flow obstruction. If problems are identified, more routine follow-up and/or treatment may be indicated.

Pediatric Pneumogram: A sleep test performed overnight in the hospital to check oxygen levels and for prolonged interruptions of breathing. This test can help identify patients at high risk for stroke or those who may benefit from adenoidectomy or tonsillectomy.

Echocardiogram: An evaluation of the structure and function of the heart. It is common for sickle cell patients to have changes in their heart size and also heart murmurs since their heart is constantly working hard due to the chronic anemia. This test is recommended every 3 years after 1 year of age.

Electrocardiogram (EKG): is a heart test to assess for heart damage or disease. This test is recommended every 3 years after 1 year of age.

Pulmonary Function Testing (PFT): Evaluates a patient’s lung functioning. PFTs are often used for pre-operative evaluation or managing patients with known lung disease. This test is recommended every year after 6 years of age.

Chest x-ray: A x-ray of the chest to look for pneumonia or lung disease. This test is recommended every 3 years after 1 year of age.

Abdominal Ultrasound: A test to visualize the structures inside the body to look for causes of upper abdominal pain, gallstones, abnormalities of the liver, spleen or kidneys, or to look for enlargements of the abdominal blood vessels. This test is recommended every 3 years after 1 year of age.

Bone Age: This test is usually a x-ray of the hand and wrist bones to determine an approximate bone age. This test is recommended at age 5 and 10 years of age.

Hip X-rays: X-ray films of the hips are helpful in diagnosing damage of the hip caused by decreased blood flow to the bones and joint space. This test is recommended every 3 years after age 5 and/or if symptoms of hip pain should develop.

Chemistry Panel: A blood test to evaluate electrolytes, kidney and liver function enzymes, glucose, cholesterol and other chemical values. Performed at least annually for general screening purposes.

Hepatitis Screen: A blood test to screen for exposure to hepatitis, performed at diagnosis for baseline studies and every three years thereafter, or annually for those on a chronic transfusion program.

Human Immunodeficiency Virus Screen: A blood test to screen for HIV. Recommended at diagnosis for baseline and yearly for patients on chronic transfusions to document safety of blood products.

Hemoglobin Electrophoresis: The blood test used to accurately diagnose sickle cell disease and determine a person’s hemoglobin type. Routinely done at diagnosis and at 2 years of age.

Ferritin: A blood test to test for level of ferritin (a protein that functions in iron storage) and often used to interpret amount of iron retained in the body for patients on chronic transfusion programs and as an indicator of the effectiveness of Desferal therapy.

Urinalysis: A urine test to check for urinary tract infection and the presence of blood, sugar or protein which could indicate other problems such as hemorrhage, diabetes, kidney or liver disease.

Red Blood Cell Phenotyping: Testing of blood for antigens for matching blood prior to transfusion therapy. Recommended at diagnosis and prior to starting transfusion program.

Transcranial Doppler Ultrasound (TCD): This is an ultrasound of the head which measures the average speed of blood flow through major blood vessels. This is an important test which is useful for stroke detection. If this test is abnormal, an MRI/MRA is recommended. TCDs are recommended every six months.

Neuropsychological Evaluations/Psychological Consultation: This is an assessment designed to assess brain functioning. Personality, coping skills, behavior, intelligence, memory, attention, visual-motor skills, language, academics and social skills may be assessed. School consultation, individual, family and group counseling, education, support, medication referrals and other services may be needed to help patients and their families understand and cope with SCD. Yearly evaluations are recommended. MRI/MRA studies are recommended when neuropsychological testing is abnormal.

Magnetic Resonance Imaging with Magnetic Resonance Angiography (MRI/MRA): This is a special three-dimensional X-ray of the brain. The MRI examines the structure of the brain and the MRA looks at the blood vessels.

Flu Shot: A vaccine to provide protection against the current flu virus. Recommended annually.

PPD: A skin test to check for sensitivity or exposure to tuberculosis. Recommended annually.

Pneumovax: A vaccine to protect against pneumoccus, a common germ that sickle cell patients are at risk for contracting. Recommended at 2 and 7 years of age.

Hepatitis B Vaccine: A vaccine to provide protection against Hepatitis B, a type of hepatitis (inflammation of the liver) infection that is commonly transmitted via blood components. Recommended for all newborns or at diagnosis if not already protected.

Social Work Assessment: A comprehensive evaluation is completed during diagnosis, transfer to our service and annually, thereafter. Ongoing assessment of the patient’s and family’s coping and adjustment to illness and prescribed treatment. Supportive services also include information and referrals to community-based agencies designed to facilitate the patient’s and family’s needs. Ongoing evaluations of patient’s developmental and maturational level as well as social issues impeding progress is also important.