Sickle cell disease is a genetic blood disorder that causes red blood cells to become misshapen and rigid. It is caused by a mutation in the gene that codes for hemoglobin. There are different types of sickle cell disease depending on whether a person inherits one or two copies of the defective gene. Common symptoms include anemia, pain crises, infections, and organ damage over time. Diagnosis involves tests like the sickle cell test, hemoglobin electrophoresis, and newborn screening to identify abnormal hemoglobin types.

1. Sickle cell
disease
Muhammad Asif Zeb
Lecturer Hematology
IPMS-KMU

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. •It’s autosomal reccessive 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 who receives only one
defective gene from either one of his
parents will develop Sickle-cell trait.
*The person that receives the defective
gene from both his parents will develop
Sickle-cell disease.
Genetics

6. 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).
*Asymptomatic :Don’t show severe symptoms as in Sickle
cell Anemia.
* HbA : 60%, HbS: 40% , HbF:<2%
*They act as carriers and can transmit the disease to their
off springs.
*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.

7. 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

8. 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.
Normal RBC Sickled RBC
*Positive sickling test associated
with a normal haemoglobin is likely
to indicate a patient with sickle cell
trait.
Positive Test
HbS
Negative Test
HbA
This test is simple and quick, used
to identify the presence of HbS.

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

10. 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.

11. Signs and Symptoms
• Vaso-occlusive crisis.(turning point of
disease after which the patient
improve or deteriorate)
• Aplastic crisis
• Splenic sequestration(anomaly or
death of part) crisis.
• Hemolytic crisis

12. 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.

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

14. 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

15. Complications
*Hand-Foot syndrome Pain,
Fever, Swelling.
*Overwhelming (great or very
large)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.

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

17. Diagnosis
Sickle test
hemoglobin electrophoresis test
Screening test for newborns DNA Analysis
CBC