Sickle Trait in Athletes

1. Sickle Trait in Athletes Andy Peterson MD MSPH

4. Substitution of a valine for glutamic acid as the sixth amino acid of the beta globin chain. Poorly soluble (alpha2-betaS2) hemoglobin Sickles and sticks together when deoxygenated Sickle Cell Disease/Trait

11. SS disease - rare in athletes Vaso-occlusive crises “A vicious viscous cycle” Frequent ischemic injuries Dactylitis Lung = acute chest Stroke Splenic Sequestration Kidney Infarct (papillary necrosis) Rhabdomyolysis Bone Marrow Failure Priapism Soft tissue/ulcers/painful crisis Infections (pneumococcus, salmonella) Significant Disability Early Death Median life expectancy 45 years1 Sickle Cell Disease 1. Platt, OS, Brambilla, DJ, Rosse, WF, et al. Mortality in sickle cell disease: Life expectancy and risk factors for early death. N Engl J Med 1994; 330:1639.

12. Hgb AS No hematologic findings 25 million Americans 8.5% of African Americans Inconsequential in most people Sickle Trait

13. Challenges • Exercise • Altitude • Heat

16. Splenic infarct at altitude Papillary necrosis Rhabdomyolysis Rare complications

17. Splenic Infarct • Ryan Clark at Denver • 2005 – “Splenic contusion” • 2007 – splenectomy • 2009 – held out

18. Splenic Infarct • Acclimatize • Can occur as low as 5500 feet • Presents with • LUQ pain • Nausea • Vomiting • Commonly misdiagnosed

19. Splenic Infarct • Descend • Rest • Hydration • Oxygen • Rarely splenectomy

20. Hematuria • Papillary necrosis • Sickling in medula • Hyposthenuria

21. Hematuria/Papillary necrosis • Hydrate • Hydrate • Hydrate • Hydrate • Hydrate • Avoid 2nd kidney injury

23. Sudden death among 2 million military recruits 1977-1981: 32.2/100,000 black recruits with AS 1.2/100,000 black recruits without hgb S 0.7 in nonblack recruits without hgb S 3 Army recruits 2008-2010 All trying to make 2 mile time standard Sudden Death With Sickle Trait Kark, JA, Posey, DM, Schumacher, HR, et al. Sickle cell trait as a risk factor for sudden death in physical training. N Engl J Med 1987; 317:781

24. Most deaths occurred during basic training1 Most occurred during 1-3 mile runs2 Sudden collapse was rare - most deaths 2 hours to 2 days later (rhabomyolitis)2 Risk of fulminant exertional rhabdomyolitis 200-fold higher in AS2 Sudden Death With Sickle Trait 1. Kark and Ward. Exercise and hemoglobin S. Semin In Hematol. 31:181-225. 2. Gardner and Kark. Fatal rhabdomolitis presenting as mild heat ilness in military training. Milit Med. 159:160-163.

25. Martin et al. Am J Med. 1989. Exercised 15 military recruits with AS Maximal exercise at 1270m and Sim4000m 1270m = 2.3% sickled cells Sim4000m = 8.5% sickled cells One recruit had 25% sickled cells and vSpO2 28% Sudden Death With Sickle Trait

26. NCAA Football 2000-2010 • No deaths on the field of play • 16 conditioning deaths • 1 weight lifting • 15 running or agility • 4 Cardiac • 1 Asthma • 1 Exertional Heat Stroke • 10 SCT

27. Math • 10 SCT deaths • 5 non-SCT deaths • 3-4% prevalence of SCT = RR 16-21!

28. The other math • 1/25,000 die of SCT per year • 0.5/25,000 die of non-SCT per year = 0.00004 absolute risk increase/year (4/1,000th of a percent attributable risk) • If limit to AA’s, 0.00008 ARI

29. 10 most recent football SCT deaths • #5 serial sprints for 5 to 25 minutes • #4 fast-tempo, multi-station drills with short rest • #1 gassers for 30 minutes

30. 1974 Colorado Ran 700m 1985 Arkansas Ran 3/4 mile 1986 Mississippi Ran 1 mile 1987 Indiana Ran 1200m 1989 Utah Ran 3/4 mile 1990 New Mexico Ran 800m 1992 Georgia Ran 1000m 1995 Arizona Ran 900m 2000 Tennessee Ran 800m 2001 Florida Intense drills 1h 2004 Ohio Ran for 10 minutes 2005 Missouri Field Drill 1h 2006 Texas Ran 1600m 2008 Florida Drills 2008 North Carolina Ran hill 15 times 2009 North Carolina Ran 700 yards 2010 Mississippi Station Drills

31. Common AS sickling situations Running for time Suicides/gassers Hard efforts 800-1200m High heat Dehydration Altitude Early in workouts

32. Multiple other studies support Weisman et al. Clin Res. 1988 Weisman et al. Am Rev Resp Dis. 1988 Gozal et al. Med Sci Sports Exerc. 1992 Freund et al. Int J Sports Med. 1995 Bile et al. Med Sci Sports Exerc. 1996 Sara et al. Clin J Sport Med. 2003 Bergeron et al. Clin J Sport Med. 2004 Marlin et al. Int J Sports Med. 2005 Connes et al. Eur J Appl Physiol. 2006 Monchanin et al. Med Sci Sports Exerc. 2006

33. Heat Cramps Early warning signs More painful/locking Pain stops exercise “Hobble to a halt” Rock hard muscles Slow response to Tx Sickling Abrupt onset - no warn Less painful (claudication) Weakness stops exercise “Slump to a stop” Soft muscles Rapid response to Tx

34. Acclimation Progressive adaptation Increased time between hard efforts Pre-hydrate Respond quickly Cool Hydrate Oxygen Have AED ready if Sx Management/Prevention

35. SPORT SPECIFFICCONDITIONING!

36. 1974 Colorado Ran 700m 1985 Arkansas Ran 3/4 mile 1986 Mississippi Ran 1 mile 1987 Indiana Ran 1200m 1989 Utah Ran 3/4 mile 1990 New Mexico Ran 800m 1992 Georgia Ran 1000m 1995 Arizona Ran 900m 2000 Tennessee Ran 800m 2001 Florida Intense drills 1h 2004 Ohio Ran for 10 minutes 2005 Missouri Field Drill 1h 2006 Texas Ran 1600m 2008 Florida Drills 2008 North Carolina Ran hill 15 times 2009 North Carolina Ran 700 yards 2010 Mississippi Station Drills

37. Dale Lloyd II • Rice 2006 • Family sued NCAA • Required screening

39. NCAA emphasis • Year round conditioning • Longer rest • Symptom recognition • Modification at altitude • Hydration • Set own pace • Build slowly • Adequate rest • Sport specific conditioning • Avoid exercise with illness • Supplemental O2 at altitude • Climate of acceptance

40. Questions