Newer Approaches to Venous Thromboembolism

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Sickle cell trait and sudden death
Hematology-Oncology Grand Rounds Nov.11,
2005 Morey A. Blinder, M.D.
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Case report
19 year old African-American male Medical history
form negative sickle cell negative Family
history No known history father was in
USMC PE 62 220 lbs BP 126/62 P 66 Skin
Normal ENT Normal Heart Normal Lungs
Normal Abdomen Normal Genitourinary
Deferred Recommendations Pass
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Case report
July 12, 2005 (summer after his freshman
year) Voluntary strength and agility
training Tuesdays were agility and lateral
movement followed by 1 hour of weight lifting 2
pm 83F relative humidity 55 Training session
started at 130 with 15 min warm up 6 stations
Players divided into groups of 3. Station 1 20
yard drill (lt 5 sec) Station 2 3 cone agility
in 30 yards (7 sec) Station 3 RACE drill (10
sec) Station 4 5 cone agility in 80 yards (No
problem sluggish) Station 5 6 bag drill in 60
yards (less then full effort)
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Case report
Station 6 Combination agility 4 separate
drills 6-8 sec each poor effort (239
pm) Post-workout stretch wobbling Fell
to ground stated vision blurry Walked off the
field with assistance to locker room.
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Case report
In the locker room Leaned on wall and slid to
floor. Described as Deep breathing Passed
out drunk Taken by landscape truck to Training
Center Carried in and placed on a table
unconscious. Defibrillator No Shock Advised
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Case report
911 notified at 308 pm Ambulance arrives at 314
pm transported to University Hospital Full
cardiac arrest with asystole ABG 7.12 pCO2
44 pO2 130 CBC Hgb 8.7 Hct 25.2 MCV 92.0 WBC
count 11,900 ANC 5,300 ALC 5,200 platelet count
160,000 Pronounced dead at 408 pm
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Death Certificate
CAUSE OF DEATH Lymphocytic meningitis,
probable viral etiology
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Football
1.5 million youth play football 75,000 in
college football 103 deaths reported
1960-2000 Death usually occurs during training
or competition
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Pathophysiology of sickle cell disease

• ?6 Glu Val
• Deoxy Hb S polymer forms with low O2, depends on
  Hgb S concentration, low pH, high temperature,
  high 2,3-DPG
• Relevant to circumstances and high risk for
  spleen, renal medulla (papillary necrosis),
  many other complications

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Sickle cell trait

• Normal
• Lifespan
• Pregnancy
• RBC parameters (Hgb, Hct, MCV,
• RDW, retic count)
• Genitourinary complications
• Hyposthenuria
• Painless hematuria
• UTI during pregnancy
• Renal medullary carcinoma (rare)
• Vaso-occlusive complications
• Splenic infarction with hypoxia
• Sudden death during extreme exertion

? globin Hgb SSD ??/?? 38.8 3.1 ??/-?
32.1 3.0 -?/-? 26.0 2.8
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Screening for Sickle Cell Trait and Disease

• RBC lysate with concentrated phosphate buffer and
  sodium hydrosulfite
• Incubate 10-20 min

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Sudden death in young athletes

Survey of autopsy-proven death in athletes lt35
y.o.
Exercise- related Heat-related
Most common Disorganized myocardial architecture
with scarring (diagnosed by echo)
History of exercise-induced chest pain or
syncope can be diagnosed by echo or angiogram
Other cardiovascular disease Accounts for many
cases of sudden death
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Athletes heart

• Structural Characteristics
• Increased cardiac mass in response to training
• Increased ventricular volume with increased wall
  thickness
• Preserved systolic function
• Most pronounced in rowing, cycling, swimming
• Isometric training wall thicknessgtvolume
• EKG changes
• Increased voltage
• Rhythm disturbances

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Other (apparent) risks unrelated to
cardiovascular disease

• Commotio cordis
• Heat stroke
• Head and spinal trauma (football players and
  pole vaulters)
• Uncontrolled asthma
• Ruptured cerebral artery aneurysm
• Arrhythmogenic supplements (ephedrine, cocaine)
• Non-penetrating blows to neck (hockey pucks)
• Sickle cell trait

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Commotio cordis

Blunt, non-penetrating, low-velocity blow to
chest (i.e. sports projectiles - baseballs,
hockey pucks) or physical contact. Directly over
heart exactly at start of repolarization Softer
baseballs and chest barriers proven effective in
swine model.
Figure 3. Stop-Frame Images of a Fatal Commotio
Cordis Event in a 14-Year-Old-Boy during a Karate
Match in Which the Unprotected Precordium
Represented a Prescribed Scoring Target.
N Engl J Med 2003 349 1064
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Sickle cell trait as a risk factor for sudden
death in physical training

• 2 million recruits in US Armed Forces underwent
  Basic Training 1977-1981
• Evaluated all sudden deaths
• Race, age and sex were known for all individuals
• Sickle trait 8 in African-Americans 0.08 in
  non-African-Americans

US Military Recruits, 1977-1981 Kark et al.
NEJM 1987 317781
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Sickle cell trait as a risk factor for sudden
death in African-Americans
with Hb AS
without Hb S
Black Recruits Cases of sudden death Rate/105
pt-yrs
37,300 13 227
429,000 5 7.6
Relative Risk 30
(p-value lt10-6 )
(95 CI 11 to 84)
US Military Recruits, 1977-1981 Kark et al.
NEJM 1987 317781
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Sickle Cell Trait as a Risk Factor for Exercise
Related Death Among All Recruits

Hb AS w/o Hb S Rate per 105 Rate per
105 Relative Risk UnexplainedDeaths among
227 7.6 30 Blacks All Deaths All
Races 244 8.8 28
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Hgb Genotype and Exercise-Related Death in
Recruit Basic Training, 1977-81
Hb AS
w/o Hb S
Total
27
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Deaths unexplained by pre-existing disease
15
13

• Rhabdomyolysis

4
1

• Heat stroke with rhabdomyolysis

3
4

• Heat stroke alone

0
2

• Unexplained sudden death

6
8
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Sudden death is young adults Autopsies of
military recruits
Non-traumatic sudden death in military
recruits Retrospective 25 years of data 108/126
were exercise-related
Eckart et al Ann Int Med 2004 141 829
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Sudden death is young adults Autopsies of
military recruits
Causes 64/126 (51) Cardiac abnormalities Corona
ry artery abnormalities 39 Myocarditis
13 Hypertrophic cardiomyopathy
8 Other 4 44/126 (35) Idiopathic 12/24
African-American deaths were sickle cell trait
() 18/126 (14) Non-cardiac
Eckart et al Ann Int Med 2004 141 829
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Deaths in U. S. Military Recruit Basic Training,
1977-90Percent of ERD explained by autopsy
findings
Military
Athletes
Explained Cardiac Death 44 84 Explained
non-Cardiac Death 6 3 Exertional Heat
Illness 27 1 Idiopathic Sudden
Death 23 12 Sickle Cell Trait 20 0.2
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Military Standards Required for Diagnosis of
Exercise-Related Deaths
Standards for all exercise-associated deaths in
the military. Thorough investigation which
includes medical command issues pertinent to
management of exercise and risk of EHI (eg Navy
JAG manual investigation) 100 timely referral
of cases with all pathologic clinical materials
to OAFME 100 measurement of body temperature
and lab tests for hemoglobinopathy, rhabdomalysis
on all sudden deaths pre-mortem, or at least when
the code is stopped.
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SCT Screening Policy History

• 1968 Cluster of 4 SCT recruits die during
  training at elevations above 4060 feet.
• 1969 Navy policy to test all recruits for Hg S
• 1970s Occupational restrictions on SCT
  aviation, diving, special forces, high altitude
  parachuting
• 1981 DoD policy requiring Services to drop their
  restrictions, but to screen for SCT. Services
  agree on a temporary cut-off of gt41 HgS as a
  point for restrictions
• 1985 DoD policy states all military
  occupational specialty restrictions on SCT are to
  be removed. This negated the 41 cutoff.
• Mid-1990s after three Air Force recruit deaths,
  Armed Forces Epidemiology Board (AFEB) asked to
  re-evaluate the benefit of SCT screening
• 1996 AFEB12
• no longer recommend routine screening for
  sickle cell trait (SCT) in the armed forces
• Recommends to continue and improve implementation
  of heat injury preventive measures

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Current DoD Screening Policies

• Army screens military occupational specialties
  (MOSs) that include aviation, diving and special
  operations, though being SCT is not
  disqualifying
• Air Force (AF), Navy and Marine Corps (MC) screen
  all recruits
• To uncover disqualifying hemoglobin disorders
• Screening is required for several MOSs, though
  being SCT is not disqualifying
• To inform individuals of SCT status and
  associated military risk
• AF allows SCT to leave service, Navy and MC
  mandate SCT to leave service if HbS gt 45.
• Navy and MC San Diego identify by medical alert
  tag. Navy Great Lakes basic training also uses
  red waistband (during physical exertion)
• Counseling is done in a group setting for AF,
  Navy and MC.

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Unanswered questions

• Will screening prevent deaths?
• Screening will identify sickle cell disease not
  identified in history. Thus it will avoid sickle
  cell crisis in those with clinically significant
  disqualifying HbS disorders during training and
  possible fatalities.
• Identification could possibly lead to more rapid
  health care for SCT or alert SCT individuals to
  follow diligently heat injury prevention policies
  which may lower the death rate
• Will screening save money?
• Should you identify sickle cell trait
  recruits/athletes?
• May increase likelihood of earlier intervention
  or provision of medical services
• Will SCT recruits be treated differently by
  peers?
• Allow identified SCT recruits to leave service
  ?

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Things to Consider

• More could be done to alleviate sudden death in
  athletes
• Cardiac screening
• Sickle cell screening
• Equipment changes
• Physical barriers and protection
• Defibrillator at all sporting events

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Pre-participation screening in athletes

Survey of 500 US High Schools 254 (50.8
responded)
Recommended screening questions
Gomez et al.Arch Pediat Adolesc Med 1999 153723
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Pre-participation screening in athletes

• 1110 NCAA College and Universities surveyed
• 879 (79 responded)
• At present, cardiac screening has limited
  potential of detecting any cardiovascular
  abnormalities

JAMA 2000283 1597
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Recommendations for screening sickle cell in
athletes and young adults

• NCAA (Committee on Competitive Safeguards and
  Medical Aspects of Sports)
• Benign condition that does not affect the
  longevity of the individual
• Not a barrier to outstanding athletic performance
• NCAA does no recommend that colleges ask
  applicants if they have sickle cell trait