DISCLOSURE Case 2 30 y/o male AA warrior referred to lab to - PDF document

Case 1  26 y/o male AA warrior, SCT Sickle Cell Trait positive, completes his PT test (push-ups, sit-ups, and 1.5 mile in Warriors and Athletes: run).  This is his fourth test; 11:30 run What We Know, What We Don’t consistent with three prior efforts. Know, and Where We Go From Here!  Ambient temperature of 50 ° F. Francis G. O’Connor, MD, MPH, FACSM  Complains of marked dizziness on Medical Director, Consortium for Health and Military Performance cool down lap. Professor and Chair, Military and Emergency Medicine Uniformed Services University of the Health Sciences, Bethesda, MD DISCLOSURE Case 2  30 y/o male AA warrior referred to lab to further evaluate  I have no relevant episode of exertional rhabdomyolysis. financial disclosures  Extremely fit prior soccer player in reference to this with no history of prior lecture. cramping.  Engages in Cross Fit workout with emphasis on squats. My opinions and assertions contained herein are private views and are not to be construed as official or as reflecting the views of the U.S. Army Medical  Awakes at night in severe back Department or the U.S. Army Service at large. pain and can’t walk. Objectives Case 3  A 20 y/o AA male midshipmen was  Review the relevant background of sickle unable to complete his fitness cell trait in warriors and athletes (WA). assessment due to severe leg pain  State what is currently known about SCT and weakness 70 yards short of completing a 1.5 mile run. in WA.  The patient had performed push-ups  State what is currently unknown about and sit-ups without difficulty SCT in WA. immediately before the run.  Discuss recommendations for where we  He was transported to the medical clinic; his only complaint was ongoing go from here . severe thigh and hamstring pain that made it difficult to walk. 1

Not Everyone is Thrilled Case 4 with Screening!  34 y/o Marine was participating in a CFT like field competition event.  He reports during his first event, a 440 m sprint, he experienced tightening and severe (10 / 10) pain approximately ¾ of way through the run.  It was all he could do to push himself across the finish whereupon he Bonham VL, Dover GJ, Brody LC: Screening student athletes collapsed and was unable to walk on for sickle cell trait--a social and clinical experiment. his own. N Engl J Med.2010 Sep 9;363(11):997-9. Background April 2010  The National Collegiate Athletic Association (NCAA) adopted a policy requiring Division I What is a Sports institutions to perform sickle cell Medicine Physician trait testing for all incoming student athletes. to Think?  Policy was partly in response to legal settlement with Dale Lloyd Case.  But then…. American Society of Request from Hematology: ASH US Army TRADOC  Two soldier deaths during basic  Policy Opposes Mandatory SCT Screening for Athletic Participation training associated with SCT – Recommends universal training  December 2010 interventions and additional research  General Martin Dempsey  Believes NCAA Division I policy, as currently written and implemented, has potential to harm student athletes and larger community of individuals with SCT . Statement on Screening for Sickle Cell Trait and Athletic Participation. (2012). ASH Policy Retrieved January 2012, from http://www.hematology.org/advocacy/policy-statements/7704.aspx 2

ACSM DoD Consensus SCT is Associated with Conference on SCT MANY Hgb Variants  Hemoglobins (Hb) are tetramers of two pairs of two types of globins, each attached to a heme subunit.  Alpha-globin gene family is located on short arm of chromosome 16 Dr. Alexis Thompson  Beta-globin gene family is located on short arm Dr. John Kark of chromosome 11. Dr. Randy Dr. Kwaku Ohene-  Each red blood cell has ~ 280 million Hb Eichner Frempong molecules.  More than 1,100 Hb variants occur and result from a wide variety of genetic events – mostly base-pair mutations in globin genes . SCT Athletes: Excel in Sports at All Levels  SCT carriers on Ivory Coast established 32/33 national records on running courses of 400 meters or shorter What is Currently – Suggests greater ability of SCT carriers to Known about perform in short and intense running events than in endurance courses. Athletes with SCT?  SCT athletes successfully competed in Olympic games in Mexico City….and the NFL. Terrell Owens Le Gallais D, et al: Point: Sickle cell trait should be considered asymptomatic and as a benign condition during physical activity. J Appl Physiol. 2007 Dec;103(6):2137-8. SCT is Common, and SCT is Associated with Generally Benign! Sudden Death  Approximately 3 million people in the “Current cumulative evidence is convincing for associations with hematuria, renal papillary necrosis, hyposthenuria, US and 300 million in the world have splenic infarction, exertional rhabdomyolysis, and SCT. exercise-related sudden death .”  Presence of SCT appears to be protective against severe falciparum malaria.  Prevalence in US: – Blacks: 1/14, – Hispanic/Latino: 1/183, – Whites: 1/625  4/10 West Africans have SCT! Tsaras G: Complications associated with sickle cell trait: a brief narrative review. Am J Med.2009 Jun;122(6):507-12. Epub 2009 Apr 24. 3

Heat Appears to be Associated *Other Causes of Death: •22 suicides with Sudden Death •12 lightening strikes •13 drownings  “Excess” sudden deaths in SCT due to •9 aneurysms Exertional Heat Illness (EHI) •8 SCT related rhabdo (<1% of Cohort) – + Sudden Cardiac Death •2 epileptic seizures, and – + Acute, Fulminant Renal Failure •4 miscellaneous  Major Predictor of heat exposure in previous 48 Hours was (WBGT > 75F) – SCT + Sudden Death: OR: 17 Dr. John Kark – EHI (SCT -) OR: 16 – Idiopathic Sudden Death – OR: 9 – Sudden Cardiac Death – OR: 5 Maron BJ, et al: Sudden death in young athletes: Analysis of 1866 deaths in the United States, 1980 -2006. Circulation 2009;119:1085-1092. Mitigating Heat Appears to Make a Difference! Big Picture Perspective 1.8 Million recruits 1.0 Million recruits  RESULTS: 37,000 SCT + 26,000 SCT + – During the 5-year period, there were 273 deaths and a total of 1 969 663 athlete participation-years. – Of these 273 deaths, 145 (53%) were due to accidents or unintentional injury, 45 (16%) from cardiac arrest, 25 (9%) No changes in training regimen Fundamental changes in training suicides, and 18 (6%) homicides. (all recruits ) regimen (all recruits) – Motor vehicle accidents accounted for 100 accidents (69%).  CONCLUSIONS : Predict Actual Lives Predict Actual Lives – Motor vehicle accidents are the most common cause of Deaths Deaths Saved Deaths Deaths Saved sudden death in athletes across NCAA divisions, gender, race, and sport. SCT + 13 0 SCT + 4 4 13 0 SCT - 19 13 6 SCT - 10 11 1 Asif IM, Harmon KG, Klossner D : Motor vehicle accidents: Total 32 13 Total 14 15 19 the leading cause of death in collegiate athletes. Clin J Sport Med. 2013 Nov;23(6):439-43. Kark et al: Exercise and hemoglobin S. Semin Hematol. 1994 Jul;31(3):181-225. Sickle Cell Trait Heat is NOT the Trigger for and Sudden Death Sickling…it’s Intensity!  Military :  EHI Not a Factor in NCAA Deaths – Study of >450,000 military recruits (1977-1981) – None of 10 NCAA football deaths – SST+ 30X risk sudden death: {RR 30 (11 – 84)} – Often NCAA collapse happens early in Kark et al: Sickle-cell trait as a risk factor for sudden workout death in physical training NEJM 1987; 317:781.  Civilian  EHI Not Proven in Army Deaths – NCAA SCT deaths 2004 to 2008 = 5. – Most Army deaths Core Temp < 102 ° F – SST +15X risk of sudden death. – Many others no Core Temp taken – D1 football players alone: SCT African Americans (AA) have a RR of 1:805; or 37x “Heat is no more a trigger for exertional sickling risk relative to those without SCT. than is altitude, asthma, heedless valor, or a Harmon et al: Sickle Cell Trait Associated with a Relative Risk of Death of 37x in reckless coach” National Collegiate Athletic Association Football Athletes: A Database with 2 Million Current Sports Med Reports, 2010, 9(6):349 Athlete-Years as the Denominator. BJSM 2012; 46(3):158. 4