Sickle Cell Anemia

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Sickle Cell Anemia
Gregg Selke, Ph.D. 11/28/06
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What is Sickle Cell Anemia (SCA)?

• First described in Chicago in 1910 by James
  Herrick as an inherited condition that results in
  a decrease in the ability of red blood cells to
  carry oxygen throughout the body

• Sickle red blood cells become hard and
  irregularly shaped (resembling a sickle)
• Become clogged in the small blood vessels and
  therefore do not deliver oxygen to the tissues.
• Lack of tissue oxygenation can cause excruciating
  pain, damage to body organs and even death.

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Mechanism

• Red blood cells (RBC)
• Contain a special protein called haemoglobin (Hb)
• Hb is the component that carries oxygen from the
  lungs to all parts of the body
• Most people have only hemoglobin type Hb A
  within RBC (normal genotype Hb AA)
• Sickle Cell HbS
• S similar to A, but one structural change
• Other types HbC, HbD, and HbE

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Mechanism -HbS

• When sickle haemoglobin (HbS) gives up its oxygen
  to the tissues, HbS sticks together
• Forms long rods form inside RBC
• RBC become rigid, inflexible, and sickle-shaped
• Unable to squeeze through small blood vessels,
  instead blocks small blood vessels
• Less oxygen to tissues of body
• RBCs containing HbS have a shorter lifespan
• Normally 120 days
• Chronic state of anaemia

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• Genetics
• 2 copies of the gene for Hb (each parent)
• HbS Recessive
• SSickle
• ANormal

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• Sickle Cell Trait
• Sickle haemoglobin (S) Normal haemoglobin (A)
  in RBC
• Adequate amount of normal Hb (A) in red blood
  cells
• RBC remain flexible
• Carrier
• Do Not have the symptoms of the sickle cell
  disorders, with 2 exceptions
• Pain when Less Oxygen than usual (scuba diving,
  activities at high altitude (12,000ft), under
  general anaesthesia)
• Minute kidney problems

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Three common types of Sickle Cell Disorders

• Sickle Cell Anemia
• Sickle haemoglobin (HbS) Sickle haemoglobin
  (HbS)
• Most Severe No HbA

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Other Sickling Disorders

• Other types of Hb combine with sickle Hb
• Hemoglobin S-C disease
• Sickle haemoglobin (HbS) (HbC)
• Hemoglobin S-Beta thalassemia
• Beta thalassaemia gene reduces the amount of HbA
  that can be made
• Sickle haemoglobin (HbS) reduced HbA
• Milder form of Sickle Cell Disorder than sickle
  cell anemia

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Some Genetic History

• The error in the hemoglobin gene results from a
  genetic mutation that occurred many thousands of
  years ago in people in parts of Africa, the
  Mediterranean basin, the Middle East, and India.
• A deadly form of malaria was very common at that
  time
• Malaria epidemics caused the death of many
• In areas where malaria was a problem, children
  who inherited one sickle hemoglobin gene and who,
  therefore, carried the sickle cell trait - had a
  survival advantage.
• Unlike the children who had normal hemoglobin
  genes, they survived the malaria epidemics they
  grew up, had their own children, and passed on
  the gene- for sickle hemoglobin.

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Sickle Cell Gene
Severe Malaria
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History

• As populations migrated, the sickle cell-mutation
  spread to other Mediterranean areas, further into
  the Middle East and eventually into the Western
  Hemisphere.
• In the United States and other countries where
  malaria is not a problem, the sickle hemoglobin
  gene no longer provides a survival advantage.
• Instead, it may be a serious threat to the
  carrier's children, who may inherit two abnormal
  sickle hemoglobin genes and have sickle cell
  anemia.

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Who is at risk?

• Most common in Africans and African Americans.
• East Asia, Southern Italy, Saudi Arabia, India,
  Egypt, South and Central American, Cuba, the
  Caribbean, Greece, and Iran, and Eastern Jews
  have also been found to have a form of this
  illness.

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Prevalence

• More than 2.5 million Americans have the trait
• 70,000 or more Americans have sickle cell disease
• About 1,000 babies are born with the disease each
  year in America
• In Nigeria, 1/3 population of U.S., 45,000-90,000
  babies with sickle cell disease are born each
  year

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• Among African - Americans
• 1 in 12 have Sickle Cell Trait (Hb SA)
• 1 in 600 have Sickle Cell Anemia (Hb SS)
• 1 in 1500 have Sickle C Disease (Hb SC)
• 1 in 350 have Sickle Cell Disease (Hb SS, SC,
  S-Beta-Thal)
• Among Latinos
• 1 in 172 have Sickle Cell Trait (Hb AS)
• 1 in 1,000 have Sickle Cell Disease (Hb SS, SC,
  S-Beta-Thal)

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Screening

• Haemoglobin Electrophoresis
• Simple Blood test
• Routine screening in high risk groups
• During pregnancy
• Before anaesthesia
• Prenatal Testing
• Amniocentesis
• 16 and 18 weeks of the pregnancy
• small risk of causing a miscarriage (1 in 100)
• Chorionic villus sampling (CVS)
• 9th or 10th week of pregnancy
• very small amount of material from the developing
  placenta
• slightly higher chance of miscarriage

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Early Symptoms and Complications

• Typically appear during infant's first year
• 1st symptom dactylitis and fever (6 mo-2 yrs)
• Pain in the chest, abdomen, limbs and joints
• Enlargement of the heart, liver and spleen
  nosebleeds
• Frequent upper respiratory infections
• Chronic anemia as children grow older
• Over time Sickle Cell sufferers can experience
  damage to organs such as liver, kidney, lungs,
  heart and spleen
• Can result in death

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Medical Complications

• kidney damage and
• loss of body water in urine
• painful erections in men (priapism)
• blood blockage in the spleen or liver
  (sequestration)
• eye damage
• low red blood cell counts (anemia)
• delayed growth

1. pain episodes
2. strokes
3. increased infections
4. leg ulcers
5. bone damage
6. yellow eyes or jaundice
7. early gallstones
8. lung blockage

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Serious Complications

• Infectious complications
• Prominent early in life
• Leading cause of morbidity and mortality
• Great improvement in the prognosis related to
  newborn screening for sickle cell disease,
  vaccination for childhood illnesses, the use of
  prophylactic antibiotics, and aggressive
  diagnosis and treatment of febrile events
• Acute splenic sequestration
• Episodes of rapid increase in splenic size and
  decrease in hemoglobin
• Potential source of morbidity and mortality early
  in life for children with sickle cell anemia and
  at any age for those with Hb SC disease and
  sickle thalassemia

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Serious Complications

• Strokes
• Up to 15 of children may have overt or silent
  strokes during childhood
• Chronic transfusion therapy reduces the
  recurrence rate of overt stroke which may
  approach 75 without intervention
• Bone disease
• Early risk is primarily from osteomyelitis
• Infectious usually painful inflammatory disease
  of bone often of bacterial origin and may result
  in bone tissue death
• Avascular necrosis of the femur and humerus
• Death of bone tissue due to disrupted blood
  supply
• Marked by severe pain in the affected region and
  by weakened bone that may flatten and collapse

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Serious Complications

• Leg ulcers
• Seen in patients older than 10 years of age
• Resistant to therapy and cause significant
  morbidity
• Ophthalmic complications
• Proliferative retinopathy, vitreous hemorrhage,
  retinal detachment
• Priapism
• Distressing complication that occurs at all ages
• Difficult to treat
• Causes a high incidence of impotence
• Chronic Anemia
• Associated with fatigue, irritability, jaundice,
  pain, delayed puberty, leg sores, eye problems,
  gum disease

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Serious Complications PAIN Recurrent Pain
Episodes or Sickling Crises

• Occur at any age but appear to be particularly
  frequent during late adolescence and early adult
  life
• Unpredictable
• Red Blood Cells get stuck in the small veins and
  prevent normal blood flow
• Characterized by severe pain in the back, chest,
  abdomen, extremities, and head
• Highly disruptive to life
• Most common reasons for individuals to seek
  health care

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Danger Signs of a Crisis

• Any sudden weakness or
• loss of feeling
• Pain that will not go away
• with home treatment
• Priapism (painful erection
• that will not go down)
• Sudden vision change

1. Fever
2. Chest pain
3. Shortness of Breath
4. Increasing tiredness
5. Abdominal swelling
6. Unusual headache

SEEK URGENT HOSPITAL TREATMENT IF IN CRISIS
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Crises

• During a crisis
• severe pain in the fingers, toes,
• arms, joints,legs, back, abdomen, and bones.
• Decrease in oxygen to the chest and lungs
• May lead to acute chest syndrome
• Damage to the lungs
• Severe pain and fever
• Lungs' airways narrow, further reducing O2
• Leads to an increased risk of potentially
• fatal infections

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Triggers of Pain

• Infections
• Thirst and dehydration caused by not drinking
  enough even if thirst is not felt
• Over-exertion
• Over-excitement
• Cold weather and cold drinks and swimming
• Bangs, bumps, bruises and strains
• Stress triggers pain in adults, but does not seem
  to do so in children.

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Predicting Pain

• Children and families can often tell when a
  severe sickle pain is coming on by
• Thirst
• Eyes turning yellow (jaundice),
• Sufferer being more irritable or tired than usual.

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Alleviating Pain

• Warmth increases blood flow
• Massaging and rubbing
• Heat from hot water bottles and deep heat creams
• Bandaging to support the painful region
• Resting the body
• Cognitive Behavioral Therapy
• Getting the sufferer to relax
• deep breathing exercises
• distracting the attention
• by other psychological methods.
• Pain-killing medicines (analgesics) paracetamol,
  codeine non-steroidal anti-inflammatory, morphine
  if necessary

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Daily Preventative Measures

1. Taking the folic acid (folate) daily to help make
   new red cells
2. Daily penicillin until age six to prevent serious
   infection
3. Drinking plenty of water daily (8-10 glasses for
   adults)
4. Avoiding too hot or too cold temperatures
5. Avoiding over exertion and stress
6. Getting plenty of rest
7. Getting regular check-ups from knowledgeable
   health care providers

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Treating Complications

• Pain-killing drugs and oral and intravenous
  fluids
• To reduce pain and prevent complications.
• Transfusions
• Correct anemia
• Treat spleen enlargement in children before the
  condition becomes life-threatening
• Regular transfusion therapy also can help prevent
  recurring strokes in children at high risk of
  crippling nervous system complications.

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Psychosocial Issues

• Require regular medical attention
• Especially before and after operations, dental
  extraction and during pregnancy.
• Adherence to medical regimen
• Vitamins, antibiotics, fluid intake, activity
  level
• Schools must be involved
• Family planning
• Suitable types of employment
• Air travel
• Increased fluids, pain killers or oxygen may be
  recommended

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Psychosocial Issues

• Child should be encouraged to participate in
  sports, but not pushed passed their limitations
• If they are in pain or feel tired they should be
  allowed to rest and keep warm.
• They should have access to drinks.
• Strenuous exercise, dehydration and cold can
  induce a crisis.
• Strenuous outdoor activities should be avoided in
  cold or wet weather
• Should only swim if the water is warm and care is
  taken to keep warm when leaving the water
• If develops a crisis despite these precautions he
  or she should avoid swimming all together

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Psychosocial Issues

• Child Specific Issues Coping with Pain
• Pain happens more often
• On an average of one third of all days
• Lasts longer
• Generally all day, even if not continuously all
  day
• Associated with great tiredness about half the
  time
• Causes them to spend significant time in bed
• On average the time spent wholly or partly in bed
  adds up to about a week of every school term.

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Psychosocial Issues

• Variability and Unpredictability
• Some are mildly affected and largely free from
  pain, while others have frequent and severe pain
• Most children go through good and bad patches
• Doctors cannot predict who will be severely
  affected.
• No easily overt detectable signs of sickle pain
• So children known to have sickle cell disorder
  who say they are in pain must be trusted
• If they can rely on the adults around them to
  take them seriously, they are less likely to take
  advantage of their condition to seek attention or
  avoid distasteful tasks.

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Psychosocial Issues

• To reduce risk of crisis, children are encouraged
  to drink much more than normal and more
  frequently
• May require about 1/4 litre of liquid every 60 -
  90 minutes.
• Child will need to go to the toilet more
  frequently
• May increase risk of Enuresis
• Boys at risk for priapism
• May be too embarrassed to mention to parents
• Severe sickling can lead to impotence

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Developing Treatments

• Hydroxyurea
• The first effective drug treatment for adults
  with severe sickle cell anemia reported in early
  1995
• Daily doses of the anticancer drug, hydroxyurea,
  reduced the frequency of painful crises, acute
  chest syndrome, needed fewer blood transfusions
• Increases production of fetal hemoglobin in the
  blood
• Fetal hemoglobin seems to prevent sickling of red
  cells
• cells containing fetal hemoglobin tend to survive
  longer in the bloodstream

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Developing Treatments

• Bone marrow transplantation
• Shown to provide a cure for severely affected
  children with sickle cell disease
• Only about 18 percent of children with sickle
  cell anemia are likely to have a matched sibling.

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• The Ultimate Cure?
• Gene Therapy
• Correcting the defective gene and inserting it
  into the bone marrow
• Turning off the defective gene and simultaneously
  reactivating another gene that turns on
  production of fetal hemoglobin.
• No real cure for Sickle Cell Anemia at this time.
• In the past 30 years, the life expectancy of
  people with sickle cell anemia has increased.
  Many patients with sickle cell anemia now live
  into their mid-forties and beyond.

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Websites
http//www.sicklecellsociety.org/ Another
Great Site information, Counselling and Caring
for those with Sickle Cell Disorders and their
families UK based http//www.sicklecelldisease.o
rg/ Sickle Cell Disease Association of
America The Human Genome Project Sickle Cell
Education Site at http//www.massinteraction.org/h
tml/genome/ http//www.ascaa.org/ American
Sickle Cell Anemia Association ASCAA was founded
in 1971 and is the oldest sickle cell research,
education, and social services organization in
the United States. http//www.ncd.gov/ http//ww
w.painfoundation.org/
 
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Sites for Kids
http//www.sicklecellsociety.org/sicklescene/pshom
f.htm Planet Sickle Cell Society (UK
based) -Youth support, Poetry, Pen-Pals,
Information, Message Board http//www.starbright
.org/ The STARBRIGHT Foundation is dedicated to
the development of projects that empower seriousl
ill children to combat the medical and emotional
challenges they face on a daily basis. Coloring
Books on Sickle Cell from Emory http//www.emory.
edu/PEDS/SICKLE/bbc/index.htm http//www.emory.edu
/PEDS/SICKLE/chelate/index.htm
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Support Group Information Florida,
Jacksonville Sickle Cell Support Groups (904)
549-4472 Georgia, Atlanta Parent SC Support
Group [phone]