ONCOLOGY/HEMATOLOGY: Sickle cell trait and neonatal hematologic screening

Sickle cell trait (SCT) is the most common genetic disorder in the United States, affecting 5% to 6% of Hispanics, 10% of persons of African origin, 2% of Asians, and 1% of northern Greeks. Worldwide, nearly 5.5 million people are estimated to carry SCT, and the World Health Organization estimates that in 2008, 3% of pregnant women were carriers. Despite this prevalence, most SCT carriers are unaware they carry the trait. According to Zora R. Rogers, MD, this is because there are a limited number of newborn screening programs and little or no interest by providers or patients in learning more about them.

In her session "Sickle Cell Trait and Other Neonatal Hematologic Screening," Rogers reviewed screening for SCT and other neonatal hematologic disorders and discussed the controversial area of newborn screening for glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency. Common in persons from Southeast Asia, sub-Saharan Africa, the Middle East, and in those from the Philippines and Taiwan, G6PD deficiency may predispose babies to high bilirubin levels that can damage the brain. Although it has been recommended that screening for G6PD be included on the newborn screening panels, she said that screening may not help prevent problems because the wide variability in the enzyme levels do not permit risk prediction.

Rogers emphasized the need for better education about SCT by focusing on the deleterious physical consequences of being a carrier and the impact on physical activity and athletics. For example, she said, people who are carriers have a probable increased risk of venous thromboembolism (but not stroke) as well as splenic infarction or left upper quadrant pain at altitude. She also discussed the potential risks for athletes with SCT, as well as recommendations on how to reduce these risks by avoiding dehydration and heat stroke.

Rogers emphasized that “sickle cell anemia or sickle cell disease has a clear risk of early death and severe morbidity throughout the life span.”

Zora R. Rogers, MD, FAAP, is professor of pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas.

Newborn screening for SCT (and disease) is currently performed in all 50 states. However, education by pediatricians about the genetic implications of SCT and potential health issues is lacking. Approximately 3 million people in the United States have SCT, and they live normal lives without serious health problems. Clinical issues such as exertional rhabdomyolysis occur in extreme conditions, including severe dehydration, very intense physical activity, or high altitudes. Education should be focused on universal precautions for athletic participation as well as general guidelines to promote a healthy, active lifestyle. Knowledge really is power. Educating patients and families about SCT will enable them to make more informed decisions for the future.

Connie Piccone, MD, is clinical director, Sickle Cell Anemia Center, and assistant professor, Department of Pediatrics, at University Hospitals Rainbow Babies and Children’s Hospital, Division of Hematology/Oncology, Cleveland, Ohio.

Despite the normal hematology profile and life expectancy of individuals with SCT, impact of SCT on health outcomes has received a great deal of attention recently. The data supporting associations of SCT with adverse events is scant and much of it is anecdotal. The relative risk of some health conditions appears to be increased, although the absolute risk is quite low because the conditions themselves are exceedingly rare.

Such is the case for exercise-related rhabdomyolysis among football players. Physicians counseling individuals with SCT must take care not to overemphasize the risks and thereby pathologize SCT, creating needless anxiety and potentially encouraging people to limit their activities unnecessarily. In particular, discouraging young people from exercising or participating in athletics is likely to have a much greater adverse impact on individual and public health than the exercise-induced events in SCT athletes. Most of these athletic training tragedies can be prevented in all athletes by sensible reforms in athletic training practices. Another example is the association of SCT with renal medullary carcinoma-very high relative risk, very low absolute risk. The solution is the universal application of the medical principle that any patient with hematuria needs an evaluation to rule out malignancy.

The long history of SCT testing illustrates that genetic information, particularly about carrier states, can be easily misconstrued by physicians, employers, insurers, and carriers themselves, resulting in misinterpretation of symptoms, misdiagnosis, discrimination, and loss of opportunity. As we understand more about the biology of SCT, it is incumbent on physicians to make sure that they and their patients are properly and accurately informed of its implications for health, without making them sick with worry.

Clinton H. Joiner, MD, PhD, is Aflac Children’s Chair for Hematology, professor of pediatrics, Emory University School of Medicine, Atlanta, Georgia, and director of hematology, Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta.