Nigel S. Key, MBChB
Harold R. Roberts Distinguished Professor and Director of the Hemophilia and Thrombosis Center at the University of North Carolina School of Medicine
On June 4 and 5, the National Heart, Lung, and Blood Institute (NHLBI) hosted a workshop at the NIH campus in Bethesda, MD, titled “Framing the Research Agenda for Sickle Cell Trait.” The purpose of the meeting was to review the current scientific understanding of the health implications for individuals with sickle cell trait. In particular, the stated purpose was to focus on “sudden death in young adults, organ system complications, and ethical, legal, social, and public health impacts.” The impetus for this workshop was the National Collegiate Athletic Association’s (NCAA) 2009 decision to recommend screening of all college athletes for sickle cell trait (SCT). This recommendation, constituting part of a legal settlement, was precipitated by the death of Dale Lloyd Jr., a football player with SCT who died in practice at Rice University in 2006. In addition to NHLBI staff and members of the academic hematology community, a number of other stakeholders were represented by delegates and speakers, including CDC’s Division of Hereditary Blood Disorders, HRSA’s Maternal and Child Health Bureau, the Uniformed Services University of the Health Sciences, and several leading organizations, such as the Sickle Cell Disease Association of America.
The agenda on the first day focused on the exercise-related complications that have been described in subjects with SCT and exertional heat illness. These complications have included exertional rhabdomyolysis with or without sudden or sub-acute death. Dr. John Kark from Thomas Jefferson University presented an update of the military experience that he originally described in a landmark paper in the New England Journal of Medicine in 1987. By studying records and autopsy reports of all sudden deaths among approximately 2 million Armed Forces recruits from 1977 to 1981, he demonstrated that, compared to African-American military recruits without SCT, subjects with the sickle trait had approximately a 30-fold risk of exercise-related death. About half of the described cases suffered exertional heat illness (rhabdomyolysis, heat stroke, and/or acute renal failure), while the remainder suffered idiopathic sudden death from cardio-pulmonary arrest. During the ensuing decade, drill instructors were trained to adjust workouts according to daily ambient temperature, to increase rest cycles and hydration, and to measure affected subjects’ core temperature in the case of suspicious early symptoms. These simple measures, applied across the board for all recruits (“universal precautions”), resulted in an enormous reduction in the rate of death related to sickle trait.
Dr. E. Randy Eichner reviewed the clinical details of the 18 cases of NCAA Division I football players who died since 1974. SCT, present in just 3 to 4 percent of Division I players, has been linked to 63 percent of reported non-traumatic deaths in the past decade. A discussion of the ethical and practical concerns surrounding the NCAA’s approach to the problem highlighted the history of community screening for SCT, which has been fraught by a number of examples of poorly conceived programs resulting in stigmatization and/or discrimination. The overall consensus seemed to be that, while it seems a reasonable priority to support studies that will result in a better understanding of the pathophysiologic mechanisms and associated (exogenous and endogenous) risk factors underlying exertion-related complications, the military experience suggests that prevention of complications in college athletes should be possible by applying universal precautions without the need to single out affected individuals for special treatment.
The second day of the workshop focused on some of the organ-specific complications of SCT. For several decades, numerous case series have reported a variety of adverse medical outcomes in individuals with SCT, and this segment was an effort to sift through those areas in which there exist not only higher quality clinical studies, but also some biologic rationale for the association. After hearing the evidence, the delegates were challenged to prioritize the areas in which further study appears warranted. By consensus, renal complications and thrombosis were thought to be the highest priority areas. Given that SCT affects approximately 3 million individuals in the United States, this may be an issue of genuine public health concern. It is very clear, however, that better data are needed before proceeding to mass screening, with all of its potential for undesirable stigmatization.
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