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By
Cheryl Hug-English M.D., MPH
October 2010
Group of inherited disorders that affect red blood
cells
 Types of Sickle Cell Disease

Sickle Cell Anemia (most severe form) two sickle
cell hemoglobin genes HbSS
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HbSC (milder form) One sickle cell hemoglobin gene
and one abnormal hemoglobin C gene
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HbS Beta Thalassemia: One sickle cell gene and
one gene for beta thalassemia (vary in severity)
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HbSD, HbSO, HbSO: rare and vary in severity
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Sickle Cell Disease:
70,000 to 100,000
cases in the US
(mostly African
Americans)
Sickle Cell Disease
occurs in about 1 out
of every 500 African
American births.
Occurs in 1 out of
36,000 Hispanic
American births*
*cdc.gov
Sickle Cell Disease is particularly common
among people whose ancestors come from:
 Sub-Saharan Africa
 South America
 Cuba
 Central America
 Saudi Arabia
 India
 Mediterranean countries (Turkey, Greece,
Italy)
 Areas of the world where malaria was a
problem…sickle cell trait, less malaria
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http://www.cdc.gov/features/sicklecell/
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Sickle Cell Disease first discovered and
reported by Dr. James Herrick 100 years ago.
Described the experience of a young student
from Grenada who came to Chicago to attend
Dental School.
Developed symptoms and sought medical
care. The sickled cells were first identified
and reported.
“World Sickle Day June 19th 2010”: 100 years
of research.
http://www.cdc.gov/features/sicklecell/
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Normal hemoglobin or HbA: 4 chains; 2 alpha,
2 beta
In Sickle Cell Disease: There is a substitution of
the amino acid valine for glutamic acid in the
beta chain, forming what is known as HbS
Valine is more hydrophobic than glutamic acid
causing the hemoglobin molecules to be
attracted to one another, forming long filaments
that distort the shape of the red blood cells and
produce the characteristic sickling
Autosomal recessive inheritance
 Inherit two genes for sickle hemoglobin (HbSS)
 Symptoms due to vasoocclusive symptoms from
sickled cells include:
 Dactylitis (acute pain and swelling in hands and
feet…often the first symptom)
 Fatigue, paleness, and shortness of breath
 Acute Pain Crisis in any body organ or joint
 Anemia
 Eye problems due to decreased blood flow to
retina
 Jaundice
 Delayed growth and puberty in children
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 Infections
(due to damage of spleen)
 Splenic sequestration crisis
 Stroke
 Multi organ involvement/failure
 Acute chest syndrome: chest pain, fever,
abnormal CXR
http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_SignsAndSymptoms.html
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NOT Sickle Cell disease
HbAS: one gene for normal hemoglobin, one
gene for hemoglobin S
Usually means about 40% of Hemoglobin in
each cell is HbS
Can pass on the trait (2 people who are
carriers of sickle cell trait have 25% chance of
having a child with sickle cell anemia)
Most often do not have hematologic
symptoms
Can lead a normal life
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2million Americans carry the Sickle Cell Trait
1 in 12 African Americans carry the Sickle Cell Trait.
Positive SCT in 8% of African Americans, 0.5%
Hispanics, 0.2% Caucasians*
*http://www.cdc.gov/features/sicklecell/
Certain circumstances or conditions can
predispose individuals with SCT to have
symptoms.
 High altitude (flying, mountain climbing)
 Increased pressure (scuba diving)
 Low oxygen (when exercising intensely,
training for athletic competitions, military
boot camp)
 Dehydation
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Identifying SCT particularly
important in athletes.
High training expectations,
intense workouts can make
them more susceptible to
having symptoms from SCT.
Despite newborn screening,
many athletes do not know
their Sickle Cell status.
Student Health is an ideal
setting to provide screening
and education for SCT
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Concern over increased risk of sudden death
in PROLONGED exercise or intense training
assumed to be associated with
rhabdomyolysis, myocardial ischemia, and
arrthymias.
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One of the first studies that looked at the risk for
sudden death was done in military recruits in 1987.
Published in the New England Journal of Medicine
(September 1987).
Looked at all deaths among 2 million recruits
undergoing basic training from 1977 to 1981.
Unexplained death rates (per 100,000) were 32.2 in
black recruits with SCT, 1.2 in black recruits without
SCT, and 0.7 in white recruits without SCT.
There were 40 deaths or near deaths that were due to
sickling. Most due to explosive rhadomyolysis.
Most deaths occurred after running 1-3 miles
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US military instituted mandatory screening for
sickle cell trait in 1982
Dramatic decrease in exercise related deaths
In fact, there were no exercise related deaths
in the military for the next ten years.
1996: Military stopped mandatory screening,
but individual service branches have own
requirements
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Study done by Van Camp et al. in 1995.
(Published in Med Sci. Sports Exercise May 1995)
Reviewed 160 nontraumatic deaths in high
school and college athletes between 1983 and
1993.
Results showed most deaths were due to
cardiovascular conditions (hypertrophic
cardiomyopathy, congenital coronary artery
anomalies)
BUT…7 deaths (4.4%) attributed to
rhabdomyolysis and sickle cell trait.
In 2007, the NATA released a consensus
statement about SCT and the Athlete
 Past 4 decades sickling had been responsible
for death of at least 15 football players
 In past seven years sickling had been
responsible for death of nine athletes: 5
college football players, two high school
athletes (one a 14 year old female basketball
player), two 12 year old boys training for
football.
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Relatively recent
death…freshman defensive
back Dale Lloyd at Rice in
2006
Collapsed after running 16
sprints of 100 yards each
Cause of death was acute
rhabdomyolysis
Parents sued Rice and the
NCAA
This triggered the NCAA to
take a closer look at this
issue
2010: NCAA issued new
mandate for SCT screening
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1974: Polie Poitier, sophomore defensive
back at Univ. Colorado dies
1975: NCAA includes section in its handbook
saying “all black athletes” should be offered a
sickle cell test”.
1987: NIH recommends screening all
newborns for SCD and trait.
2001: Devaugn Darling, twin of NFL player
Devard Darling dies during off season
conditioning at Florida State
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2002: Basketball player Kourtni Livingston, 14,
dies in Texas after running laps
2006: All states require screening for sickle cell
trait at birth
2007: NFL requires screening for sickle cell trait
2007: Ryan Clark, safety for Pittsburgh Steelers
has his spleen and gall bladder removed as a
result of sickling after playing in a game at high
elevation in Colorado
2009: NCAA recommends testing of student
athletes for sickle cell trait
2010: NCAA mandates testing for sickle cell
trait, allowing students to decline with a waiver.
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Starting August 1, 2010: All Division 1
student athletes must be tested for sickle cell
trait OR
Show proof of a prior test OR
Sign a waiver releasing an institution from
liability if they decline to be tested
Colleges and universities are expected to
provide educational information about SCT to
student athletes
Divisions II and III are currently studying
potential SCT testing
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This applies to incoming athletes. Returning
athletes are not required to be given the test.
Transfer student athletes must receive the
test.
Sickle cell testing should be done for all
athletes regardless of racial or ethnicity
status.
The results of the Sickle Cell test must be
available before a prospective student athlete
is permitted to participate.
Severe Hypoxemia
 Metabolic acidosis
 Hyperthermia in muscles
 Red Blood Cell dehydration
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Dehydration causes an osmotic shift
Water leaves the RBC, causing more sickling
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With intense exercise, more oxygen taken up
by the muscles
Hemoglobin becomes deoxygenated
Deoxygenated hemoglobin causes sickling in
RBCs more easily
Metabolic acidosis shifts
oxygen dissociation curve
to the right, causing
hemoglobin to become
deoxygenated…more
sickling
• Increased temperature
shifts curve to the right…
more sickling
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Sprinting…the harder and faster athletes run,
the greater the chance for sickling (800 1200 meters)
Many of the football deaths occurred after
sprint drills or “stadium” drills
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Cardiac Condition
A heat Illness
Asthma
Sickling
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Cardiac Collapse: tends to be instantaneous,
no cramping, inability to talk
Asthma: Slow crescendo, wheezing, chest
tightness, without cramping or pain
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Heat Collapse: prodrome of muscle twinges
before cramping starts. Pain excruciating,
muscles become locked up and rock hard.
Usually occurs later in a work out with extreme
heat. Body core temperature can be elevated.
Sickling Collapse: Usually occurs within first half
hour onfield as during windsprints. No
prodrome of muscle twinges. Muscles look and
feel normal. Athlete usually collapses with
muscles feeling weak. Pain not as excruciating.
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Collapse from sickling often early in a
workout after sprinting activities
Heat Illness after more prolonged activity
Pain from sickling milder with weakness.
Muscles feel and look normal. Athletes feel
“wobbly”.
Pain from heat exhaustion excruciating with
rock hard muscles..muscles lock up in full
contraction. Athletes “hobble” to a stop
Sickling has no prodrome
Heat cramping often has a prodrome
Response differs:
 10-15 minutes after cooling, sickling pain
improves. Muscles have regained oxygen and
begin to function normally.
 Heat cramping often takes 1-2 hours even
with massage, stretching and IVs.
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*NATA Consensus Statement 2007
Fast action necessary including:
 Oxygen
 Cooling
 Check Vital Signs
 Often with these simple steps, athlete will
improve
 If no immediate improvement, call 911, start
IV fluids, attach AED, preparing for transport
 Tell hospital to be prepared for severe
Rhabdomyolysis
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What happens with rhabdomyolyis?
 Breakdown of muscle fibers
 Release of protein Myoglobin into
bloodstream
 Myoblobin and breakdown products can
cause kidney damage
 Damaged muscle tissue also causes fluid to
move from the blood into the muscle, leading
to decreased intravascular fluid volume and
decreased blood flow to the kidney
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Weakness of muscles
 Fatigue
 Abnormally dark urine (red or brown)
 Labs:
 High CPK
 High serum creatinine
 Positive serum myoglobin
 Positive urine myoglobin
 High serum potassium
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Aggressive fluid rehydration to try to prevent
or minimize kidney damage
May need dialysis if severe
Correct hyperkalemia or hypocalcemia if
present
Sooner treatment is begun, better prognosis
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Depends on severity
Athletes with mild sickling symptoms who are
treated early with rest, hydration and cooling,
may return to play as early as the next day.
Athletes who have had true rhabdomyolysis with
hospitalization and dialysis may never return to
play due to kidney damage
In between: those who have elevated creatine
kinase, but no elevation in serum creatinine or
indication of kidney damage, may have muscle
weakness and soreness for a week or two. May
return to play gradually.
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Build up slowly in training with paced
progressions
Allow longer periods of rest and recovery
between repetitions
Encourage participation in preseason strength
and conditioning programs
Athletes with SCT should be excluded from
participation in performance tests such as
mile runs, serial sprints etc.
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Stop activity with onset of symptoms
(cramping, pain, weakness, inability to catch
breath, fatigue)
All athletes with SCT to set their own pace
Adjust work cycles for environmental heat
stress, emphasize hydration, no workout if an
athlete with SCT is ill, modify training when at
high altitude
Encourage athlete to report any symptoms
immediately
Screening:
 Hemoglobin S solubility test: (Sickledex)
Older test. Add chemicals to patient’s blood
sample that reduces amount of oxygen. Can
detect HbS, but does not distinguish between
SCD and SCT. Should not be used in infants
less than 6 months (still have HbF).
 If this test is used, any positives should be
evaluated further with Hb electrophoresis.
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To identify types and relative amounts of
various hemoglobins
These tests separate the hemoglobins so that
they can be quantified.
Hemoglobin Electrophoresis
Hemoglobin Fractionation by HPLC (high
pressure liquid chromatography)
Isoelectric focusing
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Although NCAA mandated SCT screening in
2010, at the University of Nevada, Reno we
started looking at this issue in 2008.
In 2008, we had done SCT testing on athletes
with problems with cramping. Identified 10
athletes who had SCT.
In 2009, initiated voluntary screening for SCT
for all athletes.
Summer 2010, mandatory screening of all
athletes
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Steps:
Informed consent obtained from student
athlete prior to the blood draw.
Option 1: undergo blood test
Option 2: provide documentation and results
of previous testing
Option 3: Written refusal of test
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All SCT results given to Head Team Physician.
Results (both positive and negative) are recorded on
the pre-participation exam form.
All student athletes with a positive SCT result are
scheduled to have a follow up visit with head team
physician.
Informational handouts on SCT given to student
athlete as part of visit.
Counseling and/or Genetic counseling is also
provided as needed.
Positive results communicated to the Athletic Trainer,
Head and Assistant coaches, and strength and
conditioning coaches for the particular sport the
student athlete is involved in.
◦ Stress the importance of immediately
reporting symptoms (e.g. difficulty breathing,
fatigue, muscle cramping or pain in lower
back or leg, sudden weakness, swelling,
tenderness) to athletic trainers, coaches, and
staff.
◦ Stop activity with onset of any symptoms.
◦ Gradual build up in lifting and conditioning
training with extended periods of rest and
recovery, especially between repetitions.
◦ Exclude from participation in “preseason
conditioning tests”.
◦ Modification of conditioning drills (no
timed sprints, no sustained running
without periods of rest).
 Discontinue all-out exertion activities of
any kind lasting beyond 2 to 3 minutes
without breathers.
 Allow student-athlete to set his/her own
pace.
◦ Emphasize hydration and implement a
hydration policy for before, during, and
after all activities.
◦ Emphasize control of any asthma, which
can worsen the sickling effect.
◦ Adjust work/rest cycles for heat stress and
altitude acclimatization. Modify activity in
extremely hot and humid conditions.
◦ Allow no workout if student-athlete is ill,
especially illnesses involving fever,
diarrhea or vomiting.
◦ Encourage pre-conditioning prior to
returning to the sport each season.
◦ Modify activities after nights of poor
sleep.
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The student athlete will be allowed to
participate after appropriate counseling
Recommendation will be provided as to
clearance for participation in intercollegiate
athletics or follow-up as deemed necessary.
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A yearly in-service review of Sickle Cell Trait
in Athletes is performed for the Sports
Medicine staff. When new staff members are
hired, they will complete a review of this
topic.
Yearly education and review of Sickle Cell
Trait in Athletes will also occur for the
Coaching Staff.
Education materials about SCT distributed
to all athletes
Policy At UNR instituted before SCT testing
 Reviewed with Coaches, trainers annually
 Policy identifies and discusses various levels
of heat illness diagnosis and treatment for:
 Heat Syncope
 Heat Cramp
 Heat Exhaustion
 Heat Stroke
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Medical Emergency
Distinguished from heat exhaustion by CNS
dysfunction in combination with a
dangerously high core body temperature
Symptoms:
High core body temperature (greater than
104 degrees)
CNS dysfunction (altered consciousness,
coma, convulsions, disorientation, confusion)
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Other symptoms include:
Hot, Sweaty skin
Rapid pulse rate (greater than 160)
Rapid respirations (greater than 20)
Decreased blood pressure
Nausea, vomiting or diarrhea
Headache, dizziness, weakness
Signs of coagulopathy (conjunctival
hemorrhages, hematuria)
Laboratory: electrolyte, liver, renal
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Can be fatal if core body temperature remains
above 104 for longer than 30-60 minutes
without treatment
“EHS has had a 100% survival rate when
immediate cooling was initiated within 10
minutes” *
*Korey Stringer Institute, Univ. of Connecticut:
http://ksi.uconn.edu/info/basic.html
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Rapid Cooling is a key factor in preventing the
development of rhabdomyolysis with SCT
Initiate cooling with SCT even sooner than most
We have ice baths located outside the training
room
We purchased an internal rectal thermometer
Policy: Call 911 but “Cool first, then transport”
Athletes are placed in ice bath until temperature
is less than 101 and then transported
If athlete has SCT and symptoms of heat stroke,
warn the ED to prepare for possible
rhabdomyolysis.
Testing 2009-10 academic year:
 120 tested, 3 positives (2.5%)
 Testing 2010-11 academic year:
 222 tested, 9 positives (4.1%)
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One of the SCT positives was also positive for alpha
thalassemia
When have both SCT and alpha Thalassemia…less
HbS (usually about 20%)
Electrophoresis of most showed HbA 60%, HbS 40%
Two of the 12 positives were female
All positive Sickledex were Positive on Electrophoresis
All athletes who were SCT positive were
African American
 Less than 5 athletes refused testing
 Eight positives were football players, 2 were
basketball players, 2 were track athletes
 ALL athletes have continued in their sport
 No athletes have had complications due to
SCT
 We have had great cooperation from coaches,
trainers in modifying workouts appropriately
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New England Journal of Medicine Article
September 9, 2010 “Perspective”
 Raises questions as to whether testing results
will in some way cause discrimination of
those athletes who test positive
 Will athletes be stigmatized
 Will they be treated differently be coaches
 Will this result alter the athlete’s self esteem
 Will it affect the athlete’s employability in
professional sports
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Education of our athletes, coaches, trainers is
key to reducing the possibility of
discrimination of those athletes with a
positive test
This is not a new test…sickle cell testing has
available since the early 1970’s.
More and more genetic testing on other
diseases is becoming available and there is
increased interest in genetic risk profiling on
many diseases
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Student Health Centers can and should play a
pivotal role in managing SCT testing
programs to ensure the educational
components are included, that the student
athlete is cared for, and that appropriate heat
illness protocols are developed.
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Great educational handouts and video on SCT
at www.NCAA.org/health-safety
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Bonham V et al. Screening Student Athletes for Sickle
Cell Trait- A social and Clinical Experiment. The New
England Journal of Medicine. 2010; 363;11: 997-999.
cdc.gov/NCBDDD/sicklecell/data.html
Eichner ER. Sickle Cell Trait. Journal of Sport
Rehabilitation. 2007;16,:197-203.
Report of the April 29,2010,meeting of the National
Collegiate Athletic Association Division 1 Board of
Directors.
http://web1.ncaa.org/web_files/DI_<C_BPD/DI_BOD/
2010/April/Board_report_Aril.pdf
Van Camp SP et al. Non Traumatic sports death in
high school and college athletes. Med Sci Sports
Exercise.1995; 27:641-7.