Sickle cell disease is an autosomal recessive disorder caused by mutations in the hemoglobin beta gene, leading to the sickling of red blood cells, with major types including sickle cell anemia and sickle cell trait. Key symptoms arise from complications such as vaso-occlusive crises and infections, and the condition is diagnosed through tests like hemoglobin electrophoresis and DNA analysis. Current treatments focus on managing symptoms, promoting fetal hemoglobin production, and preventing complications, with genetic counseling recommended for affected families.

1. Sickle cell
disease
By: Yara Mostafa
Yasser Mostafa
Yasser Osama

2. Sickle Cell Disease
• RBCs disorder that causes
the sickling of biconcave
shaped RBCs.
• There are many types:
*Sickle cell Anemia.
*Sickle cell Trait.

3. Distribution of Sickle cell Anemia

4. Brief Medical History
1910 – First Description of Sickle-Shaped
Blood Cells by Dr James Herrick.
1917 – Genetic basis for SCD were discovered
by Dr. V. Emmel.
1922 – Disease was named “sickle cell
anaemia” by Vernon Mason .
1927 – Hahn and Gillespie elaborated on
Emmel’s work by demonstrating that the
sickling effect was linked to de-oxygenation.
Dr James B. Herrick

5. Pathophysiology
• Deoxy Hb S polymer forms with
low O2, depends on Hgb S
concentration, low pH, high
temperature, high 2,3-DPG
• Membrane is damaged so RBCs
accumulate calcium, lose
potassium & water and
become rigid & irreversibly
sickled
• Sickle cells hemolyze within 10-
20 days

6. Genetics
•It’s autosomal recessive blood disease.
•It’s not contagious “You can’t catch it”.
•You inherit it from your parents.
*The gene defect is a known mutation of a
single nucleotide.
*The person that receives the defective
gene from both his parents will develop
Sickle-cell disease.
*The person who receives only one
defective gene from either one of his
parents will develop Sickle-cell trait.

7. Sickle Cell Trait (AS)
*A person has one abnormal allele of the hemoglobin
beta gene.
*Those who are heterozygous for the sickle cell allele
produce both normal “HbA” and abnormal hemoglobin
“HbS” (the two alleles are co-dominant).
* HbA : 60%, HbS: 40% , HbF:<2%
*Asymptomatic :Don’t show severe symptoms as in Sickle
cell Anemia.
*People with sickle cell who exercise heavily, such as
athletes and those who are exposed to dehydration or
altitude extremes, may sometimes experience sickle cell
anemia symptoms.
*They act as carriers and can transmit the disease to their
off springs.

8. *It has been suggested that sickle cell trait is linked to two other
medical problems that may elicit health and performance concerns.
These include:
1) Exercise-related rhabdomyolysis 2) Exercise-associated sudden death
(skeletal muscle breakdown)
* Occur in normal, healthy individuals *Sickle cell trait deaths occurred
following strenuous exercise. predominantly in football players.
*Sickle cell trait individuals might be at *Athletes with the trait experienced
greater risk for developing the syndrome noninstantaneous collapse with
than those without this trait. gradual but rapid deterioration, ie,
* This syndrome can result in renal dyspnea, fatigue, weakness, and
failure and sudden death. muscle cramping.

9. Diagnosis
Sickle test
solubility tests
hemoglobin electrophoresis test
Screening test for newborns DNA Analysis

10. Sickling Test
Method:
1) A sample of venous blood or capillary blood may be collected for this test.
*Venous blood from the arm.*Capillary blood from the finger tips or ear lobes and in
infants from the heel of the foot.
2) Mixing blood with the reducing agent, sodium metabisulphite, will induce sickling in
susceptible cells.
3) the results can be viewed under a microscope after 20 minutes.
Negative Test This test is simple and quick, used Positive Test
HbA to identify the presence of HbS. HbS
Normal RBC Sickled RBC
*Positive sickling test associated
with a normal haemoglobin is likely
to indicate a patient with sickle cell
trait.

11. Sickle Solubility Test (SST)
•A rapid and inexpensive technique used to screen for the presence of sickling
hemoglobins, can be used at home.
•A positive result must be confirmed by another method (HPLC or electrophoresis) to
confirm the presence of Hb S and to distinguish Hb AS (carrier state) from Hb SS
(sickle cell disease).
•Disadvantage: Other insoluble hemoglobins, such as Hb C-Harlem, will also give a
positive result.
Method: Depend on phosphate solubility
1) Erythrocytes are lysed by saponin.
2) The released hemoglobin is reduced by
sodium hydrosulfite in a phosphate buffer.
The presence of HbA under The resulting tactoids of HbS
3) Reduced HbS is characterized by its very
these same conditions results causes the solution to remain
low solubility andred solution. of
in a clear the formation turbid.
neumatic liquid crystals (tactoids).

12. Hemoglobin Electrophoresis test
* Haemoglobin electrophoresis will differentiate between homozygous and
heterozygous conditions.
* Hemoglobin types have different electrical charges and move at different speeds.
*HbAS: Has both HbA and
HbS.
Shows 2 bands
*HbSS: Is less negative by 2
compared to HbA .
Migrates slower than HbA

13. Newborn screening
• It is performed via the most sensitive Hb isoelectric
focusing or HPLC fractionation and identifies the
specific types of hemoglobin present.
•In newborns who carry the sickle cell gene, fetal
hemoglobin F will predominate, but a small
amount of hemoglobin S will also be present.
•There also may be a small amount of hemoglobin
A if they have sickle cell trait.
DNA analysis
• This test is used to investigate alterations and mutations in the genes that produce
hemoglobin components.
•It may be performed to determine whether someone has one or two copies of the
Hb S mutation or has two different gene mutations.
•Genetic testing is most often used for prenatal testing: The usual tests offered are
chorionic villus sampling (CVS) or amniocentesis “14 to 16 weeks”.

14. Globin Gene Family
Chromosome 16
1 Zeta
Alpha Family
2 Alpha
Globin Gene
1 Epsilon
Family
2 Gamma
Beta Family
1 Beta
Chromosome 11
1 Delta

15. HbF
*If fetal hemoglobin remains the predominant form of hemoglobin after birth, the
number of painful episodes decreases in patients with sickle-cell disease.
*The fetal hemoglobin's reduction in the severity of the disease comes from its ability to
inhibit the formation of hemoglobin aggregates within the red blood cells also containing
hemoglobin S.
*A form of treatment of Sickle cell
anemia is hydroxyurea that promotes
the production of fetal hemoglobin

16. Signs and Symptoms
• Infection, dehydration, and acidosis act as
triggers but in most instances no predisposing
cause is identified.
• They usually appear after 4 months of age.
• Most common signs are linked to Anemia and
Pain.

17. Signs and Symptoms
• Vaso-occlusive crisis.
• Aplastic crisis
• Splenic sequestration crisis.
• Hemolytic crisis

18. Vaso-oclusive crisis
• Ischemia
• Pain
• Necrosis
• Often leads to organ damage
• Management
– Severe: analgesics, Opioid
– Mild: NSAIDs
– New treatment involving
*Adenosine A2a receptor
agonists. These medicines may
reduce pain-related
complications.

19. Splenic squestration crisis
• Acute, painful enlargements of the spleen,
caused by intrasplenic trapping of red cells
• Caused by intrasplenic trapping of red cells
• Die within 1-2 hours due to circulatory failure
• Autosplenectomy

20. Aplastic crisis
• Paravirus B19
– Divides in RBCs precursors and destroys them
– Stops erythropoiesis for two or three days
– Causes reticulocytopenia
– Disappears within one week with management and
blood transfusions
Hemolytic crisis
• Common in patients with G6PD deficiency

21. Complications
*Hand-Foot syndrome Pain,
Fever, Swelling.
*Overwhelming post-splenectomy
infection (OPSI) treated
with antibiotics and supportive care.
*Acute chest Syndrome Chest
pain, Shortness of breath, Fever.
*Stroke Learning problems,
Long term disability, Brain damage,
Paralysis, Death.
*cholelithiasis (gall stones) & Cholecytitis
Nausea, Vomiting, Jaundice,
Sweating, Clay-coloured stool.

22. Complications
*Priapism Damge to the Penis and
Impotence.
*Retinopathy Blindness.
* Sickle cell nephropathy Chronic
renal failure.
*Pulmonary hypertension Fatigue,
Shortness of breath.
*In pregnancy spontaneous abortion.
*Aseptic bone necrosis.

23. Management
• Blood transfusions:
– Acute chest crisis OH
O
– Decreases the risk for strokes
– Defrasirox: iron chelator
• Folic acid daily intake N N
• Penicillin N
*
• Malaria chemoprophylaxis OH
* *
HO
Fe

24. Treatment
• Hydroxyurea.
– Reactivates fetal Hb production
– Decreases severity of attacks
– Increases life span
– More effective with Erythropoietin.
• Bone marrow transplant during childhood.
• 5-HMF. This natural compound binds to red blood cells and
increases their oxygen. This helps prevent the red blood cells
from sickling.

25. Prevention
• You can’t prevent sickle cell
anemia, because it’s an inherited
disease.
• If a person is born with it, steps
should be taken to reduce
complications.
• Genetic Counseling should be
considered.
• A counselor can explain the risk of
having a child who has the disease
and can help explain the choices
that are available.

26. Prognosis
*New and aggressive treatments for sickle cell disease are prolonging life and
improving its quality.
*Recently as 1973, the average lifespan for
people with sickle cell disease was only 14
years.
*Currently, life expectancy for these
patients can reach 50 years and over.
*Women with sickle cell live longer than
their male counterparts.
*The median age at death :
-Males : 53years
-Females: 58 years
*As children with sickle cell disease live longer, older patients are now facing medical
problems related to the long-term adverse effects of the disease process.

27. Malaria
• Parasitic infection: Plasmodium falciparum
• Two stages in the human body:
– Exoerythrocytic stage in liver (8 to 30 days)
– Erythrocytic stage

28. Sickle cell gene and malaria
• Heterozygous individuals are tolerant to
malaria
• Homozygous individuals are less tolerant to
malaria because of the common functional
asplenia

29. Why?
Direct contact HO-1 and
with sickle blood brain
cells barrier

33. Heme oxygenase-1

34. Refrences
• Harper’s illustrated Biochemistry
• Lippincott’s illustrated reviews of Biochemistry
• Robbins basic Pathology
• American society of hematology

35. Thank You