Sickle cell disease
Muhammad Asif Zeb
Lecturer Hematology
IPMS-KMU
Sickle Cell Disease
• RBCs disorder that causes
the sickling of biconcave
shaped RBCs.
• There are many types:
*Sickle cell Anemia.
*Sickle cell Trait.
Distribution of Sickle cell Anemia
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
Genetics
•It’
s autosomal dominant 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.
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.
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
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.
Neg ative 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.
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
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.
Signs and Symptoms
• Vaso-occlusive crisis.
• Aplastic crisis
• Splenic sequestration crisis.
• Hemolytic crisis
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.
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
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
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.
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.
Diagnosis
Sickle test CBC
hemoglobin electrophoresis test
Screening test for newborns DNA Analysis
