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Kathryn C/ Lambert, D.O., FAOASM

}  Understand the impact of Sickle Cell Disease and Sickle Cell Trait (SCT) on sports participation

}  Be aware of NCAA policy regarding SCT }  Recognize the clinical presentation of

exercise collapse associated with SCT (ECAST) }  Identify the risk factors for SCT complications }  Develop strategies to prevent exercise related

complications associated with SCT

}  Genetic disorder of hemoglobin production ◦  1st clinically identified in 1910 ◦  Reported as genetic condition 1949 ◦  Hemoglobin abnormality in 1951

}  Sickle Cell Disease – inherit two sickle cell genes – one from each parent

}  Sickle Cell Trait – inherit one sickle cell gene

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}  Normal Hb (HbA) – 2 alpha and 2 beta globin proteins

}  Sickle Hb (HbS) – 2 alpha and 2 sickle beta globin }  Each RBC has many Hb molecules to deliver

oxygen from the lungs to the tissues where it is needed

}  SCD = 85+% of Hb is HbS }  SCT = 35-55% of Hb is HbS

}  There are actually multiple genes for globin proteins – so manifestations of SCD/SCT can vary

}  Deoxygenated HbS forms hydrophobic bonds that deform the RBC into a crescent

}  These “sickle” cells that are “sticky” and rigid

together with proinflammatory mediators clog vessels resulting in vaso-occlusive events

}  Results in acute ischemia (crisis), chronic end organ damage and hemolysis

}  Level of oxygen in the cell – Lower O2 results in more deoxyHbS ◦  high altitudes worse ◦  deconditioned pt without enhanced cardiac output

}  pH level – Low ph promotes deoxygenation ◦  Exercise induced acidosis worse

}  Tissue temperature – higher temps promote deoxygenation

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}  Hydration – Dehydration increases viscosity ◦  promotes hypercoaguable state

}  Age ◦  Death rate in SCT 8x higher for 28-29yo vs. 17-18yo ◦  Etiol?...may be from chronic renal papillary necrosis

and resultant inability to concentrate urine

}  How much HbA or other hemoglobinopathy -may reduce sickling ◦  SCT carriers may vary in the amounts of HbS

}  SCD typically unable to participate as over-exertion and competitive sports involve factors that promote sickling/crisis

}  With the Dx of SCD in the 1950’s – SCT was initially believed to be a benign condition with little to no health consequence

}  1975 - NCAA statement –SCT not a barrier to achieving the highest levels of athletic performance

}  1970 (NEJM, JonesSR, et al) US Army reports 4 deaths over 1 year during basic training at 4,050 ft altitude

}  1987 (NEJM, Kark JA et al) Army retrospective review of all deaths from 1977-1981 showed Black recruits with SCT had 30 fold higher risk of sudden death

}  1995 (MSSE, Van Camp et al) – ten year review of nontraumatic sports-related deaths includes 7 caused by exertional rhabdomyolysis associated with SCT

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}  Intl J Sport Med - Bile et al - }  Large epidemiologic study of track and field

athletes 1956-1995 }  Higher % SCT in field throw and jump champions ◦  ? Does SCT benefit in brief explosive events ◦  How? - Vincent et al showed SCT has greater type II

muscle fibers }  SCT may limit performance in activities requiring

sustained aerobic metabolism ◦  lower cytochrome C oxidase activity – so lower oxidative

energy metabolism at the tissue level.

}  2000-2010 – 9 of 21 deaths of collegiate football players linked to SCT

}  Sept 2006 – Dale Lloyd II dies at Rice University after sprinting 100 yds. for the 16th consecutive time

}  Wrongful death suit – led to NCAA policy change ◦  2009 – recommend determining SCT status ◦  April 2010 – All Division 1 athletes MUST be tested for SCT,

have proof of prior test or sign waiver of liability if they decline testing

}  US - all newborns are screened for SCD }  Solubility test – “Sickledex” ◦  2009 CDC consensus group (Grant et al-Am J

Prevent Med 2011) –recommended against this test in favor or more reliable screens

}  Hemoglobin electrophoresis }  Other – ◦  Liquid chromatography ◦  DNA testing

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}  Seen highest frequency in persons of African American and Middle Eastern descent – but also among those of Mediterranean or Indian origin. (Jordan et al – Am J of Prev Med 2011)

}  300million carriers of SCT worldwide

}  3-4 million SCT in US, ◦  8-9% of the African Americans in US

}  Splenic infarction ◦  Ryan Clark – Steelers safety Nov 2007 playing

game in Denver }  Renal papillary necrosis }  Hematuria

}  Exertional Rhabdomyolysis (ER) }  Exercise-related sudden death

}  19 yo African American college FB player ◦  apparently healthy ◦  PMH of seasonal allergies and ?EIA at age 13 (SOB

and fatigue when started baseball)

}  Late September workout – turf temp 76o with mild wind

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}  4:00PM – weight training indoors

}  4:30PM – outdoors for 16-100 yard sprints ◦  Breaks of 1-2 min between each sprint

}  4:55PM – completes sprints but c/o SOB and leg pain – is alert

}  5:05PM – becoming lethargic but still conscious; +SOB - legs too weak to support weight – University EMS contacted – taken indoors - O2 begun

}  5:12PM – University EMS arrives – IVF started - O2 100% via bag valve mask – Fire Dept EMS called

}  5:28PM – Fire Dept EMS arrives

}  5:28PM – FD EMS Assessment: pt unconscious with shallow respirations – ◦  Glascow Coma score of 3 ◦  POx on room air 62% - 100% with high flow O2 ◦  EKG = sinus tach with peaked t waves in V2-V3

}  Nasally intubated }  Rushed to ED – arrives 5:52PM

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}  Emergency Department findings ◦  BP151/49 , P126, R30, T97

}  7PM Lab results ◦  ABG= pH 7.05, PCO2 45mmHg PO2 540mmHg ◦  Lactic acid 33mmolL (ULN=2.2) ◦  Serum bicarbonate 8mEq (LLN =24) ◦  Serum Creat = 2.3 ◦  Phosphorus = 12.8 (ULN =4.5) ◦  Potassium = 5.2

}  7PM Labs (cont.) ◦  Creatine Kinase = 536 (ULN=220) ◦  Myoglobin = 7485 (ULN=72) ◦  CSF – nml ◦  Drug Screen - neg ◦  CBC nml (Hb=14.5) ◦  PT=23, PTT=84, Fibrinogen=87, Fibrin Sp Prod >20

}  EKG=peaked T waves }  CXR= Nml

}  Through the night the patient was given: ◦  IVF, IV antibiotics, renal dialysis, ◦  20UFFP, 10UpRBC, 4UPlatelets

}  Hb dropped to 4.3 }  CK climbed to >41,000 }  Potassium climbed to over 9

}  Pt died 15 hours after admission

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}  Consortium for Health and Military Performance (CHAMP) -September 2011 –Bethesda

}  Experts from the DOD, ACSM, AMSSM, NCAA, ASH and others

}  Charge ◦  Training recommendations to mitigate risk of

strenuous exercise with SCT ◦  Develop to identify, treat, and RTDP for nonfatal

collapse

}  Report – MSSE – O’Connor FG, et al. 2012

}  Repeated high intensity exercise w/ little or no rest in between ◦  Serial sprints ◦  Fast-tempo multi-station drills

}  Near maximal exertion – “all out / heroic” effort sustained for several minutes

}  Early in training (deconditioned) }  Hot temperatures }  High altitudes

}  Athlete reports muscle pain AND weakness }  Muscles look and feel normal to examiner ◦  Differs from heat cramps- no locked up muscles

}  Athlete slumps to ground but typically can talk at first ◦  Differs from cardiac arrest

}  Rapid tachypnea from lactic acidosis – but moving air well ◦  Differs from acute asthma attack

}  Rectal temp <103 ◦  Differs from Heat stroke

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}  Athlete collapses and unresponsive ◦  EMS/CPR/ AED/ Tx for shock/ VS incl temp and

cool if appropriate/ IV access/Oxygen/ ED transport

}  Athlete collapses and responsive ◦  Brief Hx/ VS incl temp and cool if appropriate/

Attach AED/ IV access/ Oxygen

◦  If no immed improvement – Transport to ED ◦  If immediate improvement – Rest/ Rehydrate and

consult with physician for graded RTP

}  Widespread intramuscular and intravascular sickling leads to vascular occlusion, endothelial damage and impaired blood flow to muscles.

}  Ischemic rhabdomyolysis }  Severe Hyperkalemia/ acidosis ◦  Lethal cardiac arrhythmia

}  May also lead to DIC

}  Appropriate progression in exercise intensity ◦  NCAA recommends that athletes with SCT should

“set their own pace”

}  Avoid repeated high intensity drills with limited to no recovery

}  Avoid some timed performance tests

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}  Prevent heat illness ◦  Strict adherence to heat acclimatization ◦  Liberal hydration ◦  Allow “heat dumping” – A/c, shade, removal of

layers ◦  Do not exercise when ill

}  Provide supplemental oxygen when needed }  Identify SCT status

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2.  Connes, Philippe, Kimberly G. Harmon, and Michael F. Bergeron. "Pathophysiology of exertional death associated with sickle cell trait: can we make a parallel with vaso-occlusion mechanisms in sickle cell disease?." British Journal of Sports Medicine 47.4 (2013): 190-190.

3.  Diaw, Mor, et al. "Effects of hydration and water deprivation on blood viscosity during a soccer game in sickle cell trait carriers." British Journal of Sports Medicine (2012).

4.  Goldsmith, Jonathan C., et al. "Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications." American journal of hematology 87.3 (2012): 340-346

5.  Harris, Kevin M., et al. "Sickle cell trait associated with sudden death in competitive athletes." The American journal of cardiology (2012). 

6.  Jordan, Lanetta B., et al. "Screening US college athletes for their sickle cell disease carrier status." American journal of preventive medicine 41.6 (2011): S406-S412. 

7.  Grant, Althea M., et al. "Public Health Implications of Sickle Cell Trait." American Journal of Preventive Medicine 41.6 Supplement 4 (2011): S435-S439. 

8.  Shelmadine, Brian D., et al. "Rhabdomyolysis and Acute Renal Failure in a Sickle Cell Trait Athlete: A Case Study." Clinical Journal of Sport Medicine 23.3 (2013): 235-237. 

9.  Tarini, Beth A., Margaret Alison Brooks, and David G. Bundy. "A Policy Impact Analysis of the Mandatory NCAA Sickle Cell Trait Screening Program." Health services research 47.1pt2 (2012): 446-461. 

10.  Werner, Eric J., Zora R. Rogers, and Holly Benjamin. "Sickle cell trait only one condition that can increase risk of sudden death during exercise." AAP News 33.9 (2012): 16-16. 

11.  O’Connor, Francis et al “Sickle cell trait: what's a sports medicine clinician to think? Br. J. Sports. Med. 2013;47:11 667-668  12.  Harmon, Kinberly et al. “Sickle cell trait associated with a RR of death of 37 times in national collegiate athletic association

football athletes: a database with 2 million athlete-years as the denominator. Br J Sports Med (2012);46:325-330   13.  O'Connor, Francis G., et al. "ACSM and CHAMP Summit on Sickle Cell Trait: mitigating risks for warfighters and athletes."

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experiment." New England Journal of Medicine 363.11 (2010): 997-999.   15.  Mitchell, Bruce L. "Sickle cell trait and sudden death--bringing it home." Journal of the National Medical Association 99.3

(2007): 300.   16.  McGann, Patrick T., Alecia C. Nero, and Russell E. Ware. "Current Management of Sickle Cell Anemia." Cold Spring Harbor

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