Ppt for sickel cell anaemia

1. SICKLE CELL
ANAEMIA
EARLY CLINICAL EXPOSURE (ECE)

2. SICKLE CELL ANAEMIA
CASE

3. A three years old male child, native of Jharkhand, Central India
presented with mild pallor, icterus, and history of on and off
abdominal and joint pains. On examination the child had mild
splenomegaly.
He had history of two prior hospital admissions. First at the age of 1
year, when he was diagnosed to have pneumonia and second, at
the age of 3 years (3 months prior to coming to our institution) for
fever, anemia and jaundice. He has had three transfusions till now,
last transfusion was 3 months back.
There is history of sibling death at 5 years of age due to fever and
jaundice.
What is the probable diagnosis?
Case Presentation

5. Case Explanation & Our Probable
Diagnosis
To confirm the disease, the biochemical and laboratory tests were performed and
their results are as follows –
CLINICAL FINDINGS:
The hemogram showed anemia with leukocytosis. Red cell morphology revealed
severe anisopoikilocytosis with macrocytes, microcytic hypochromic red cells,
target cells, many boat cells, sickled RBCs, polychromatic cells and occasional
nucleated RBCs.

6. Results of the automated blood cell counts showed –
Hb 7.7 g/dL (Normal range: 12 -14g/dL)
RBC 2.44 million/cm^3 of blood (Normal range:4-6 million/cm^3 of blood)
MCV 97.1 fL (Normal range:78-96 fL)
MCH 31.4 pg (Normal range:27-33pg)
MCHC 32.3 g/dL (Normal range:32-37g/dL)
There were occasional nucleated red cells and relative neutrophilia. Further to
confirm HbS, a sickling test using freshly prepared 2% sodium meta-bisulphite was
performed which was positive.
This indicates that the person suffers from SICKLE CELL ANEMIA.

7. Introduction – Sickle Cell Anemia
• The glutamic acid in the HbA is changed to valine in HbS
This single amino acid substitution leads to polymerization
of hemoglobin molecules inside RBCs. This causes a
distortion of cell into sickle shape.
• The substitution of hydrophilic glutamic acid by
hydrophobic valine causes a localized stickiness on the
surface of the molecule. The deoxygenated HbS may be
depicted with a protrusion on one side and a cavity on the
other side, so that many molecules can adhere and
polymerize. HbS can bind and transport oxygen. The
sickling occurs under deoxygenated state.
• The sickled cells form small plugs in capillaries. Occlusion
of major vessels can lead to infarction in organs like spleen.
Death usually occurs in the second decade of life.
• The heterozygous state is very common in Central and
West Africa as well as in East and Central parts of India.

8. Genetic Basis (Molecular Basis)
Sickle cell Anemia is the autosomal
recessive genetic disorder. The root cause
of sickle cell disease is due to a single
base-pair point mutation in the β-globin
gene resulting in the substitution of the
amino acid valine for glutamic acid in the
β-globin chain. Sickled haemoglobin
tetramers polymerised in low oxygen
tension . This causes damage to the
erythrocytes and converts biconcave
erythrocytes into sickle shaped .

9. Biochemical Mechanism
(Pathophysiological Changes)
Pathophysiological changes include:
(1 ) intravascular hemolysis releases Hb into circulation;
(2) endothelial cell dysfunction and NO resistance;
(3) resultant hypercoagulable state contributing to vaso-occlusive crisis.
The sickled cells form small plug in capillaries. Occlusion of major vessels
can lead to infarction in organs like spleen. Clinical heterogeneity is seen
when different variants are coinherited. HbC in heterozygous state
produces mild hemolysis. Inheritance of HbS and HbC together causes
mild sickle cell disease (SC disease), since the S and C copolymerize. HbA
and HbF do not copolymerize with S. Hence in HbAS condition and in
persistence of HbF, sickling does not occur when pO2 is normal. The HbS
can bind and transport oxygen. The sickling occurs under deoxygenated
state.

10. Occurence of Disease (Distribution in
World)
Sickle cell disease is more common in certain ethnic groups including:
People of African descent, including African-Americans (among whom 1 in 12
carries a sickle cell gene) Hispanic-Americans from Central and South
America People of Middle Eastern, Asian, Indian, and Mediterranean descent.
Because sickle cell disease symptoms can begin by four months of age, early
diagnosis is critical. All newborns in the United States are now tested for the
disease. Sickle cell disease can be identified before birth by testing a sample
of amniotic fluid or tissue from the placenta.
People who carry the sickle cell gene can seek genetic counseling before
pregnancy to discuss options.

12. Difference Between Homo- and
Hetero-zygous Condition
In sickle cell anemia, the condition is caused by a mutation in the HBB gene that
codes for the beta-globin subunit of hemoglobin. This mutation results in the
production of abnormal hemoglobin known as hemoglobin S (HbS).
Now, let's explore the differences between homozygous and heterozygous
conditions:
1. Homozygous Sickle Cell Anemia (HbSS):
• In this condition, an individual inherits the HbS mutation from both parents. -
• The genotype is SS (homozygous), meaning both alleles for the beta-globin
gene carry the sickle cell mutation.
• - Individuals with HbSS have a more severe form of sickle cell disease,
experiencing recurrent pain episodes, anemia, and other complications.

13. 2. Heterozygous Sickle Cell Trait (HbAS):
• In this condition, an individual inherits the HbS mutation from one parent and
a normal hemoglobin allele (HbA) from the other parent. -
• The genotype is AS (heterozygous), meaning one allele carries the sickle cell
mutation (S) and the other carries the normal allele (A). -
• Individuals with HbAS usually do not experience severe symptoms of sickle
cell disease. They are carriers of the trait and are generally asymptomatic.
However, under certain conditions, such as low oxygen levels or dehydration,
some individuals with the sickle cell trait may experience complications.In
summary, homozygous sickle cell anemia (HbSS) involves inheriting the sickle
cell

15. Mechanism of Sickling:
Sticky patches and Formation of the
DeoxyHb Fibres
As we know,
In Sickle Cell Anaemia, there is the substitution of valine for glutamate, which
results in the formation of sticky patch on the outer surface of B chains of
both oxy- and deoxy-Hb S.
These sticky patches are absent on Hb A.
There is a site or receptor complementary to sticky patch on the beta chains
ofdeoxy-Hb S and deoxy-Hb A.

16. Sickling process in Deoxy-Hb S:
The sticky patch of one deoxy-HbS bindswith the receptor of another deoxy-HbS
resulting in the formation of long aggregate molecules of deoxy-HbS.Thus, the
polymerization of deoxy-Hboccurs and leads to the formation of long fibrous
precipitates. These stiff fibres distort the shape of erythrocytes into a sickle or
crescent shape and they become highly vulnerable to lysis.
Sickling process in Oxy-Hb S:
Although the sticky patch is present on the outer surface of beta chains, the
complementary receptors are masked. Hence, the molecules of Oxy-HbS
cannot bind among themselves or with the molecules of deoxy-HbS to form the
aggregates. No aggregate formation is seen.
Sickling process in Deoxy-Hb A:
Deoxy-Hb A lack sticky patches but contain receptor. Hence, the absence of sticky
patches does not allow the deoxy-HbA to participate in the formation of
aggregates.

17. Sickling process in Oxy-Hb A:
Since, no sticky patches and complementary receptors are present on the B
chains, it does not contribute to the formation of long aggregates.
SICKLING IS THE POLYMERIZATION OF DEOXY-HB S.
Therefore, if Hb S is maintained in the oxygenated form or with minimum Deoxy-
Hb S, sicking can be prevented.

18. Relation With Malaria
HOW DOES SICKLE CELL ANAEMIA PROVIDE RESISTANCE TO MALARIA ?
1. Multiple studies found that P. Falciparum ring-stage parasites did not grow in
HbAS red blood cells under low oxygen tension. Parasite growth was inhibited in
both sickled and non-sickled HbAS red blood cells.
2. It has been hypothesized that specific intra-erythrocytic conditions of HbAS
red blood cells, such as low intracellular potassium, high concentrations of
haemoglobin or osmotic shrinkage of the red blood cell cause an inhospitable
environment for parasites.

19. 3. Recent data provide support for the intriguing possibility that human
micro RNAs translocated into parasite mRNA reduce intra-erythrocytic
growth. This study found two human micro RNAs that were highly enriched in
erythrocytes with HbAS, and these micro RNAs inhibited translation of
specific parasite mRNA transcripts negatively impacting parasite growth in
vitro.
4. Rosette formation, which is the binding of P. Falciparum-infected red blood
cells to uninfected red blood cells, is thought to lead to microcirculatory
obstruction in cerebral malaria. Rosette formation was found to be impaired in
P. Falciparum-infected HbAS red blood cells under deoxygenated conditions.
5. Reduced cytoadherence of HbAS and HbSS erythrocytes likely leads to
increased splenic clearance, and may in part explain lower parasite densities
and a lower incidence of severe malaria in HbAS individuals.

21. Sickling Test
• The sickle cell test looks for the abnormal hemoglobin in the blood that causes
the disorder sickle cell disease.
• When whole blood is mixed with strong reducing agent such as sodium
dithionite Deoxygenation of RBC does occur.
• If the RBC contains sickle hemoglobin (HbS) ,they become sickle shaped
• RESULT: Immediate sickling positive is an indication of HbS (sickle cell
haemoglobin). But if sickling occurs after 1-2hrs of after 12 hrs , it is suggestive
of sickle cell Hb traits.

23. Electrophoretic Analysis
Charge Impact of amino acid substitution:
• HbS (sickle hemoglobin) is less negatively charged than HbA (normal
hemoglobin) due to the neutral nonpolar valine residues.
• Reduced negative charge influences the electrophoretic mobility of HbS.
Electrophoresis at Alkaline pH:
• During electrophoresis, proteins migrate toward the anode (positive
electrode) based on their charge.
• At alkaline pH, HbS migrates more slowly toward the anode compared to HbA
due to its lower negative charge.
Clinical Application:
• Electrophoresis of hemoglobin obtained from lysed RBCs is routinely used for
diagnostic purposes.
• Enables the identification of sickle cell trait and sickle cell anemia based on
the distinctive migration pattern of HbS.

25. Management Of Sickle Cell Anemia
• Edu. of the family and child
• Early intervention for problems such as
fever
• Administer antibiotics acc. to prescription
• Adequate hydration to prevent sickling
• Early recognition of resp. problems
• Alternative pain management technique,
behavior modification program, relaxation
therapy, hypnosis, music therapy, message
and transcutaneous electrical nerve
stimulation
• Give primary immunizations as well as
pneumococcal, HIB, hepatitis and trivalent
influenza vaccine.

26. Test To Detect Genes (Investigations)
• The Sickle cell anemia (HBB) gene analysis (exon 1) – and the HPLC- Sickle Cell
Anemia test(to check the type of haemoglobin present in your blood) can tell
you whether you are at risk of passing on the condition to your future children
and if you have sickle cell disease yourself.
• Sickle cell disease can be diagnosed in an unborn baby by sampling some of the
amniotic fluid surrounding the baby in the womb
• The most popular methods for detecting these diseases are the full count of
blood cells, Hb electrophoresis, and high-performance liquid chromatography
(HPLC). These methods are considered the gold standard in the diagnosis of
SCD

27. Earliest Cases Of Sickle Cell Anemia
ORIGIN –
Mutation causing sickle cell disease arose in Africa thousands of years ago.
While sickle cell disease affects people across the world of all backgrounds,
the greatest number of affected patients in the U.S. Are those with African
ancestry.
EARLIEST CASES –
First case: 1910
Dr. James Herrick had a patient, Walter Noel who displayed symptoms of what we
now refer to as acute chest syndrome, which is a common complication of Sickle
cell disease. The blood film of the patient clearly showed the characteristic shape
of sickle hemoglobin.

28. Second case: 1911
A female patient had previously been diagnosed with a form of pernicious Anemia.
She had a blood film that clearly demonstrated the form of sickle hemoglobin cells.
Third case: 1915( suggestion of a genetic link)
Blood film of this patient’s father was examined. there were no abnormalities
evident in the fresh blood sample, some abnormal cells were evident after a few
days. This was the first time that the disease was seen as an inherited condition.

29. Milestones In Sickle Cell Anemia
• 1910 - James Herrick notes "peculiar, elongated sickle-shaped erythrocytes"
in a patient with anemia.
• 1930s - Lemuel Whitley Diggs suggests that pain in sickle cell patients is due
to sickle cells clogging up small blood vessels.
• 1941 - Linus Pauling discovers that sickle cell disease is caused by an abnormal
hemoglobin.
• 1957 -Vernon Ingram discovers that a change in one amino acid in hemoglobin
S causes sickling.
• 1970s - Sickle cell anemia becomes the first human disease to be explained at
the level of a single nucleotide mutation.
• 1972 - The Sickle Cell Anemia Control Act allocates government funding for
screening, research, and treatment. With these funds, the National Heart,
Lung, and Blood Institute establishes the Cooperative Study of Sickle Cell
Disease.

30. • 1980 - Robert P. Hebbel observes that sickle cells stick to the lining of blood vessels
and shows that this correlates with severity of illness.
• 1983 - The Prophylactic Penicillin Study (PROPS) finds that treatment of well sickle
cell patients with penicillin could prevent death related to serious infections.
• 1995 - The Multicenter Study of Hydroxyurea proves the usefulness of hydroxyurea in
preventing complications in patients with sickle cell disease.
• 1996 - The Multicenter Bone Marrow Transplant Study demonstrates a cure for
children with sickle cell disease.
• 1998 - The Stroke Prevention in Sickle Cell Disease clinical trials show that transcranial
Doppler ultrasonography, a method of analyzing blood flow in the brain, is an effective
screening tool.
• 2000 - A published study by Lennette J. Benjamin demonstrates that a day hospital
for the treatment of pain improves quality of life and prevents hospitalizations.
• 2001 - Gene therapy successfully cures a sickle-cell mouse.
• 2005 - Genetic methods are developed to predict complications of sickle cell disease.

31. New Treatment Options For Sickle Cell
Anemia
• Medicine to prevent the sickling of red blood cells is Voxelotor treats sickle
cell disease in adults and children 4 years old and older. The oral medicine
prevents red blood cells from forming the sickle shape and binding together.
• Possible side effects include headache, diarrhea, abdominal pain, nausea,
fatigue, and fever. Rarely, allergic reactions may occur, causing rashes, hives,
or mild shortness of breath.
• Medicine to reduce vaso-occlusion and pain crises, Crizanlizumab-tmca is
approved for adults and children 16 years old and older who have sickle cell
disease. The medicine, which is given through an intravenous (IV) line in the
vein, helps prevent blood cells from sticking to blood vessel walls and causing
blood flow blockage, inflammation, and pain crises.

32. • Hydroxyurea is an oral medicine that has been shown to reduce or prevent
several complications of sickle cell disease.
• Use in adults: Many studies of adults with hemoglobin SS or hemoglobin Sβ
(sickle cell beta) thalassemia showed that hydroxyurea lowered the number of
episodes of pain crises and acute chest syndrome. It also improved anemia
and reduced the need for transfusions and hospital admissions.
• Use in children: Studies in children with severe hemoglobin SS or Sβ
thalassemia showed that hydroxyurea lowered the number of vaso-occlusive
crises and hospitalizations.
• Penicillin taken twice a day helps lower children's chance of having a serious
infection in the bloodstream.
• Acute transfusions treat complications that cause severe anemia.

33. • FDA approved L-glutamine for people age 5 and older to lower the number of
pain crises.Increasing the circulating levels of Hb-F which decreases the RBC
sickling is also helpful.
• Blood Transfusion increase the number of red blood cells and also provide
normal red blood cells that are more flexible than red blood cells with
sickle hemoglobin.
• A blood and bone marrow transplant is currently the only cure for sickle cell
disease, but it is not for everyone
• These transplants usually use a matched donor. Blood and bone marrow
transplants are riskier in adults

35. Statistics Regarding Sickle Cell
Anaemia In India
WHAT DO THEY INDICATE ?
India is one of the top country having sickle cell anemia patient which is about 20
millionAs of my last knowledge update in January 2022, here are the general
statistics regarding sickle cell anemia in India and their implications:
1. Prevalence: Sickle cell anemia has a significant presence in certain tribal
communities across various regions in India, notably in states like Maharashtra,
Madhya Pradesh, Chhattisgarh, Odisha, and parts of southern India. The
prevalence tends to be higher among these specific ethnic groups.
2. Geographic Distribution: The disease is geographically concentrated in areas
where certain tribal populations reside. The prevalence may vary significantly
between regions, and it primarily affects specific communities.

36. 3. Health Impact: Sickle cell anemia poses considerable health challenges,
leading to chronic pain, anemia-related complications, increased susceptibility
to infections, and organ damage. This affects the affected individuals' overall
health and quality of life.
4. Healthcare Challenges: Limited access to healthcare resources, diagnostic
facilities, and specialized care remain significant hurdles in managing and
treating sickle cell disease in these regions.
5. Government Efforts: The Indian government has initiated various programs
focusing on increasing awareness, providing genetic counseling, offering
testing services, delivering treatment support, conducting research
collaborations, and launching public awareness campaigns. These efforts aim
to address the disease burden and improve healthcare services for affected
communities.

37. ● These statistics collectively highlight
the necessity for targeted interventions,
better healthcare infrastructure, and
ongoing efforts to mitigate the impact of
sickle cell anemia on affected
populations in India.
● For the most recent and detailed
statistics regarding sickle cell anemia in
India, including any changes or updates
since 2022, consulting updated research
studies, governmental health reports, or
relevant health organizations would
provide the latest information and
insights.

38. Prognosis Of Sickle Cell Anemia
• Differentiation of the genotype-phenotype relationship of spinocerebellar
ataxia subtypes helps to improve the prognosis.
• Although it takes a long time to appreciate the full range of the signs and
symptoms, it is almost irreversible once it is evident.
• But, the symptomatic treatment may improve the prognosis. Survival depends
upon the length of CAG repeat expansion.
• One longitudinal cohort study concluded that the average 10-year survival
rate of SCA1 is only 57%, while that of SCA6 is 87%. SCA complicated by
dysphagia has the shortest survival rate.

39. Clinical Findings And Correlations -
Symptoms
• Requires a medical diagnosis.
• Infections, pain and fatigue are symptoms of sickle cell disease.
• People may experience:
Pain areas: in the joints
Pain types: can be sudden in the chest
Whole body: dizziness, fatigue, low oxygen in the body, or malaise
Urinary: inability to make concentrated or dilute urine or blood in urine
Also common: abnormal breakdown of red blood cells, inflamed fingers
or toes, pallor, shortness of breath, or yellow skin and eyes

40. Follow-ups For The Patient
• Build relationships with a hematologist and a team of other specialists so thare
available for you when needed.
• Healthy lifestyle
• Stay active
• Drink8-10 glasses of water daily
• Follow a heart healthy eating plan that includes limiting alcohol
• Aim for 7-8 hours of sleep a night
• Prevent infection
• Children under 5years old should take penicillin regularly
• Adults and children should get scheduled vaccines,including flu shots
• Wash hands often
• Good health care
• Work closely with your doctor to develop your own unique care plan.

42. Questions
1. What is the primary cause of sickle cell anemia?
a. Bacterial infection
b. Genetic mutation
c. Viral infection
d. Environmental factors
Explanation:
b. Genetic mutation - Sickle cell anemia is caused by a genetic mutation affecting
the hemoglobin gene.

43. 2. What symptoms are characteristic of sickle cell anemia during a crisis?
a. Fatigue and dizziness
b. Joint pain and swelling
c. Headaches and migraines
d. Shortness of breath and chest pain
Explanation:
b. Joint pain and swelling - During a crisis in sickle cell anemia, patients often
experience severe pain, particularly in the joints.

44. 3. How is sickle cell anemia inherited?
a. Autosomal dominant
b. X-linked recessive
c. Autosomal recessive
d. Y-linked recessive
Explanation:
c. Autosomal recessive - Sickle cell anemia is inherited in an autosomal recessive
manner, meaning both parents must carry the mutated gene for a child to
inherit the disorder.

45. 4. What is the primary strategy for preventing complications in sickle cell
anemia?
a. Vaccination
b. Genetic counseling
c. Blood donation
d. Hydration
Explanation:
d.Hydration - Adequate hydration is crucial in preventing complications
associated with sickle cell anemia, as it helps to reduce the risk of sickle cell
crises.

46. 5. What is the recommended treatment for managing pain in individuals
with sickle cell anemia?
a. Antibiotics
b. Blood transfusion
c. Pain medications
d. Surgery
Explanation :
c. Pain medications - Pain management with medications, including analgesics, is
a common approach to alleviate the intense pain experienced during sickle
cell crises

47. THANK YOU!
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