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Exertional sickling: questions and controversy

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      Abstract

      Sickle cell trait (SCT) occurs in about 8% of African-Americans and is often described to be of little clinical consequence. Over time, a number of risks have emerged, and among these are rare but catastrophic episodes of sudden death in athletes and other individuals associated with physical activities which is often described as exercise collapse associated with sickle trait (ECAST). Despite an epidemiologic link between SCT and sudden death as well as numerous case reports in both medical literature and lay press, no clear understanding of the key pathophysiologic events has been identified. Strategies for identification of individuals at risk and prevention of ECAST have been both elusive and controversial. Stakeholders have advocated for different approaches to this issue particularly with regard to screening for hemoglobin S. Furthermore, the recommendations and guidelines that are in place for the early recognition of ECAST and the prevention and treatment of the illness are not well defined and remain fragmented. Among the cases identified, those in collegiate football players in the United States are often highlighted. This manuscript examines these case studies and the current recommendations to identify areas of consensus and controversy regarding recommendations for prevention, recognition and treatment of ECAST.

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      Most cited references 24

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      Blood and muscle pH after maximal exercise in man.

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        Sickle-cell trait as a risk factor for sudden death in physical training.

        Case reports of sudden death during exertion have not established an association between the sickle-cell trait (hemoglobin AS) and exercise-related death. To test this association, all deaths occurring among 2 million enlisted recruits during basic training in the U.S. Armed Forces in 1977 to 1981 were classified from autopsy and clinical records as non-sudden deaths or as sudden deaths explained or unexplained by preexisting disease. On the basis of known numbers of entering recruits (according to race, age, and sex) and published prevalence rates for hemoglobin AS (8 percent for black and 0.08 percent for nonblack recruits), death rates (per 100,000) were 32.2 for sudden unexplained deaths, 2.7 for sudden explained deaths, and 0 for non-sudden deaths among black recruits with hemoglobin AS, as compared with 1.2, 1.2, and 0.7 among black recruits without hemoglobin S and 0.7, 0.5, and 1.1 among nonblack recruits without hemoglobin S. Among black recruits the relative risk of sudden unexplained death (hemoglobin AS vs. non-hemoglobin S) was 27.6 (95 percent confidence interval, 9 to 100; P less than 0.001), whereas among all recruits this risk was 39.8 (95 percent confidence interval, 17 to 90; P less than 0.001). The relative risk of sudden unexplained death among all recruits increased with age (P less than 0.04), from 13 (ages 17 to 18) to 95 (ages 26 to 30). We conclude that recruits in basic training with the sickle-cell trait have a substantially increased, age-dependent risk of exercise-related sudden death unexplained by any known preexisting cause.
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          Fatalities in high school and college football players.

          Fatalities in football are rare but tragic events. The purpose was to describe the causes of fatalities in high school and college football players and potentially provide preventive strategies. Descriptive epidemiology study. We reviewed the 243 football fatalities reported to the National Center for Catastrophic Sports Injury Research from July 1990 through June 2010. Football fatalities averaged 12.2 per year, or 1 per 100,000 participants. There were 164 indirect (systemic) fatalities (average, 8.2 annually [or 0.7 per 100,000 participants]) and 79 direct (traumatic) fatalities (average, 4.0 annually [or 0.3 per 100,000 participants]). Indirect fatalities were 2.1 times more common than direct fatalities. The risk of a fatality in college compared with high school football players was 2.8 (95% CI, 0.7-8.2) times higher for all fatalities, 3.6 (95% CI, 2.5-5.3) times higher for indirect events, 1.4 (95% CI, 0.6-3.0) times higher for direct injuries, 3.8 (95% CI, 1.8-8.3) times higher for heat illness, and 66 (95% CI, 14.4-308) times higher for sickle cell trait (SCT) fatalities. Most indirect events occurred in practice sessions; preseason practices and intense conditioning sessions were vulnerable periods for athletes to develop heat illness or SCT fatalities, respectively. In contrast, most brain fatalities occurred during games. The odds of a fatality during the second decade, compared with the first decade of the study, were 9.7 (95% CI, 1.2-75.9) for SCT, 1.5 (95% CI, 0.8-2.9) for heat illness, 1.1 (95% CI, 0.8-1.7) for cardiac fatalities, and 0.7 (95% CI, 0.4-1.2) for brain fatalities. The most common causes of fatalities were cardiac failure (n = 100, 41.2%), brain injury (n = 62, 25.5%), heat illness (n = 38, 15.6%), SCT (n = 11, 4.5%), asthma and commotio cordis (n = 7 each, 2.9% each), embolism/blood clot (n = 5, 2.1%), cervical fracture (n = 4, 1.7%), and intra-abdominal injury, infection, and lightning (n = 3, 1.2% each). High school and college football have approximately 12 fatalities annually with indirect systemic causes being twice as common as direct blunt trauma. The most common causes are cardiac failure, brain injury, and heat illness. The incidence of fatalities is much higher at the college level for most injuries other than brain injuries, which were only slightly more common at the college level. The risk of SCT, heat-related, and cardiac deaths increased during the second decade of the study, indicating these conditions require a greater emphasis on diagnosis, treatment, and prevention.
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            Author and article information

            Affiliations
            [1 ]Departments of Medicine and Pathology and Immunology, Washington University , St. Louis, MO
            [2 ]University of Notre Dame , Notre Dame, IN, USA
            Author notes
            Department of Internal Medicine and Pathology and Immunology, Division of Hematology, Campus Box 8125, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. +1.314.362.8814 - +1.314.362.8813. mblinder@ 123456dom.wustl.edu

            Contributions: the authors contributed equally.

            Conflict of interests: the authors declare no potential conflict of interests.

            Journal
            Hematol Rep
            Hematol Rep
            HR
            Hematology Reports
            PAGEPress Publications, Pavia, Italy
            2038-8322
            2038-8330
            03 December 2014
            19 November 2014
            : 6
            : 4
            4274478
            10.4081/hr.2014.5502
            ©Copyright M.A. Blinder and S. Russel

            This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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            Figures: 0, Tables: 2, Equations: 0, References: 38, Pages: 5
            Categories
            Article

            Hematology

            sudden death, exercise collapse, sickle cell trait

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