ByCheryl 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 HbSC (milder form) One sickle cell hemoglobin gene

and one abnormal hemoglobin C gene HbS Beta Thalassemia: One sickle cell gene and

one gene for beta thalassemia (vary in severity) HbSD, HbSO, HbSO: rare and vary in severity

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 AfricaSouth AmericaCubaCentral AmericaSaudi Arabia IndiaMediterranean countries (Turkey, Greece,

Italy) Areas of the world where malaria was a

problem…sickle cell trait, less malaria http://www.cdc.gov/features/sicklecell/

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/

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

Infections (due to damage of spleen)Splenic sequestration crisisStrokeMulti organ involvement/failureAcute chest syndrome: chest pain, fever,

abnormal CXR

http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_SignsAndSymptoms.html

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

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

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

Concern over increased risk of sudden death in PROLONGED exercise or intense training assumed to be associated with rhabdomyolysis, myocardial ischemia, and arrthymias.

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

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

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.

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

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

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.

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

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

Dehydration causes an osmotic shift Water leaves the RBC, causing more

sickling

With intense exercise, more oxygen taken up by the muscles

Hemoglobin becomes deoxygenated Deoxygenated hemoglobin causes sickling

in RBCs more easily

• Metabolic acidosis shiftsoxygen dissociation curveto the right, causing hemoglobin to become deoxygenated…moresickling• Increased temperatureshifts curve to the right…more sickling

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

Cardiac Condition A heat Illness Asthma Sickling

Cardiac Collapse: tends to be instantaneous, no cramping, inability to talk

Asthma: Slow crescendo, wheezing, chest tightness, without cramping or pain

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.

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.

*NATA Consensus Statement 2007

Fast action necessary including:OxygenCoolingCheck Vital SignsOften with these simple steps, athlete will

improve If no immediate improvement, call 911, start

IV fluids, attach AED, preparing for transportTell hospital to be prepared for severe

Rhabdomyolysis

What happens with rhabdomyolyis?Breakdown of muscle fibersRelease of protein Myoglobin into

bloodstreamMyoblobin and breakdown products can

cause kidney damageDamaged 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

Weakness of muscles Fatigue Abnormally dark urine (red or brown) Labs:High CPKHigh serum creatininePositive serum myoglobinPositive urine myoglobinHigh serum potassium

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

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.

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.

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.

To identify types and relative amounts of various hemoglobins

These tests separate the hemoglobins so that they can be quantified.

o Hemoglobin Electrophoresiso Hemoglobin Fractionation by HPLC (high

pressure liquid chromatography)o Isoelectric focusing

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

Steps:o Informed consent obtained from student

athlete prior to the blood draw.o Option 1: undergo blood testo Option 2: provide documentation and

results of previous testingo Option 3: Written refusal of test

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.

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.

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 SyncopeHeat CrampHeat ExhaustionHeat Stroke

Medical Emergency Distinguished from heat exhaustion by CNS

dysfunction in combination with a dangerously high core body temperature

Symptoms: o High core body temperature (greater than

104 degrees)o CNS dysfunction (altered consciousness,

coma, convulsions, disorientation, confusion)

Other symptoms include:o Hot, Sweaty skino Rapid pulse rate (greater than 160)o Rapid respirations (greater than 20)o Decreased blood pressureo Nausea, vomiting or diarrheao Headache, dizziness, weaknesso Signs of coagulopathy (conjunctival

hemorrhages, hematuria)o Laboratory: electrolyte, liver, renal

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

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%)

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

New England Journal of Medicine ArticleSeptember 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

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

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.

Great educational handouts and video on SCT at www.NCAA.org/health-safety

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.