Transcript Sickle haemoglobin (HbS)

Sickle Cell Anemia
Gregg Selke, Ph.D.
11/28/06
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.
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
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
Genetics
 2 copies of the gene
for Hb (each parent)
 HbS –Recessive
 S=Sickle
 A=Normal
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
1. Pain when Less Oxygen than usual (scuba diving,
activities at high altitude (12,000ft), under general
anaesthesia)
2. Minute kidney problems
Three common types of
Sickle Cell Disorders
1. Sickle Cell Anemia

Sickle haemoglobin (HbS) + Sickle haemoglobin (HbS)

Most Severe – No HbA
Other Sickling Disorders
Other types of Hb combine with sickle Hb
2. Hemoglobin S-C disease

Sickle haemoglobin (HbS) + (HbC)
3. 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
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.
Sickle Cell Gene
Severe Malaria
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.
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.
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
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-BetaThal)
Among Latinos

1 in 172 have Sickle Cell Trait (Hb AS)

1 in 1,000 have Sickle Cell Disease (Hb SS, SC, SBeta-Thal)
Screening
1. Haemoglobin Electrophoresis


Simple Blood test
Routine screening in high risk groups
• During pregnancy
• Before anaesthesia
2. 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
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
Medical Complications
1. pain episodes
2. strokes
3. increased infections
4. leg ulcers
9. kidney damage and
loss of body water in urine
10. painful erections in men
(priapism)
5. bone damage
11. blood blockage in the spleen
or liver (sequestration)
6. yellow eyes or
jaundice
12. eye damage
7. early gallstones
13. low red blood cell counts
(anemia)
8. lung blockage
14. delayed growth
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
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
Serious Complications
 Leg ulcers
 Seen in patients older than 10 years of age
 Resistant to therapy and cause significant morbidity

Ophthalmic complications


Priapism




Proliferative retinopathy, vitreous hemorrhage, & retinal detachment
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
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
Danger Signs of a Crisis
1. Fever
2. Chest pain
3. Shortness of Breath
4. Increasing tiredness
7. Any sudden weakness or
loss of feeling
8. Pain that will not go away
with home treatment
5. Abdominal swelling
9. Priapism (painful erection
that will not go down)
6. Unusual headache
10. Sudden vision change
SEEK URGENT HOSPITAL TREATMENT IF IN CRISIS
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
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.
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.
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
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
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.
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
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
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.
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.
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
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
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.
The Ultimate Cure?
Gene Therapy
1. Correcting the “defective gene” and inserting it
into the bone marrow
2. 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.”
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.org/: Sickle Cell Disease Association of
America
The Human Genome Project Sickle Cell Education Site at
http://www.massinteraction.org/html/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://www.painfoundation.org/
Sites for Kids
http://www.sicklecellsociety.org/sicklescene/pshomf.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
Support Group Information:
Florida, Jacksonville: Sickle Cell Support Groups (904) 549-4472
Georgia, Atlanta: Parent SC Support Group (404) 616-4395