Sickle cell disease is a genetic blood disorder caused by a mutation in the gene that codes for hemoglobin. It results in rigid, sickle-shaped red blood cells that can block blood vessels. The lecture outlines the definition of sickle cell disease and sickle cell anemia, their genetic inheritance, clinical manifestations such as pain crises and organ damage, diagnostic testing including blood smears, and principles of management including hydration, antibiotics, blood transfusions, penicillin prophylaxis, and potential complications. The goal is for students to understand the etiology, types of crises, clinical features, investigations, and treatment approach for sickle cell disease.

1. Sickle Cell Disease
DR BRIGHT RAICE SIAMUNYANGA

2. OBJECTIVES
By the end of this lecture students should be able to
• Define sickle cell disease,and Sickle cell anemia
• Outline the etiology
• Outline the types of crisis in Sickle cell
• List the clinical manifestations.
• List the investigations (screening and diagnostic)
• Outline the principles of management.
1/24/2020 DR SIAMUNYANGA BRIGHT 2

3. Normal Vs. Sickle Red Cells
NORMAL
• Sickle-Shaped
• Rigid
• Lives for 8-20 days or less
SICKLE CELL
• Disc-Shaped
• Deformable/flexible
• Life span of 120 days
1/24/2020 DR SIAMUNYANGA BRIGHT 3

4. Sickle Cell Anaemia
1/24/2020 DR SIAMUNYANGA BRIGHT 4

5. Definition
SCD is a genetic condition characterized by the
inheritance of two abnormal genes: One coding for
Haemoglobin S and the other for another abnormal
Haemoglobin.
SCA is a genetic condition characterized by the
inheritance of two abnormal genes both coding for
Haemoglobin S
1/24/2020 DR SIAMUNYANGA BRIGHT 5

6. What causes sickle cell disease
• Sickle cell disease is an inherited disease
caused by a genetic mutation. Genes are
found on structures in the cells of our body
called chromosomes. There are normally 46
total, or 23 pairs, of chromosomes in each cell
of our body. The 11th pair of chromosomes
contains a gene responsible for normal
hemoglobin production.
1/24/2020 DR SIAMUNYANGA BRIGHT 6

7. • A mutation in this gene is what causes sickle
cell disease. This mutation is thought to have
originated in areas of the world where malaria
was common, since people with sickle trait do
not get malaria. The sickle trait actually
protects them from the parasite that causes
malaria, which is carried by mosquitoes
1/24/2020 DR SIAMUNYANGA BRIGHT 7

8. • Children who inherit the genetic
mutation from both parents will have
sickle cell disease. Children who inherit
the mutation from only one parent will
not have the disease, but will carry the
trait for it and can pass it on to their
children.
1/24/2020 DR SIAMUNYANGA BRIGHT 8

9. SCD INHERITANCE
1/24/2020 DR SIAMUNYANGA BRIGHT 9

10. Mechanism
Substitution of glutamic acid by valine at
the 6th position
Negatively charged amino acid replaced by
neutral amino acid.
1/24/2020 DR SIAMUNYANGA BRIGHT 10

11. mechanism…cont
– Hb S maintains normal function in oxygenated
state
– In de-oxygenated state- induced change in
configuration allows valine to interact irregularly
– Formation of highly ordered polymers
– Polymers aggregate to rigid rods
– Spiny brittle RBCs
– Within vessels, thrombosis/obstruction
1/24/2020 DR SIAMUNYANGA BRIGHT 11

12. SCD PERIPHERAL SMEAR
1/24/2020 DR SIAMUNYANGA BRIGHT 12

13. Frequency
• Predominantly Negroid and Asia
• Mutation believed to have originated in Africa
• Heterozygosity believed to be as high as 30%
in some parts of sub Saharan Africa
1/24/2020 DR SIAMUNYANGA BRIGHT 13

14. Types of Sickle cell crisis
1. Aplastic crisis
• Following infection with Parvovirus
B19
2.Hyperhemolytic crisis
3.Splenic sequestration
4. Vaso occlusive crisis
1/24/2020 DR SIAMUNYANGA BRIGHT 14

15. Manifestations
• Generally, no symptoms are seen until after 3 months
of age when there is switch from production of
Gamma (ý) chains to β chain. Foetal Haemoglobin to
Adult Haemoglobin
• Dactylitis (aka hand-foot syndrome)
– Painful, symmetric swelling of hands and feet
– Due to ischemic necrosis of small bones of hands
and feet
– Due to rapidly expanding bone marrow, choking of
blood supply
1/24/2020 DR SIAMUNYANGA BRIGHT 15

16. DACTYLITIS IN SCA
1/24/2020 DR SIAMUNYANGA BRIGHT 16

17. CLINICAL MANIFESTATIONS IN SCA
1/24/2020 DR SIAMUNYANGA BRIGHT 17

18. Manifestations
• Acute pain episodes
– Young children- extremities
– Older patients- head, chest, abdomen, back
– Recurrence of pain tends to occur in same sites
within a particular individual
– Exacerbated by fever, hypoxia,
– acidosis- promote deoxygenation of Hgb S
1/24/2020 DR SIAMUNYANGA BRIGHT 18

19. SICKLE CELL
1/24/2020 DR SIAMUNYANGA BRIGHT 19

20. Manifestations
• Infarctions
– Bone/bone marrow
• Osteomyelitis- concern of salmonella infection
– Auto splenectomy
• By 3-4 years most would not have a functioning spleen
• Increased susceptibility to encapsulated organisms
– Esp. pneumococcus & H. influenzae
– Associated with reduction in serum opsonins
– Pulmonary infarcts
• Pneumonitis
• Fat emboli
1/24/2020 DR SIAMUNYANGA BRIGHT 20

21. Manifestations
• Infarcts
– Stroke
– Kidney
• Impaired renal function
• Hyposthenuria
• Priapism
• Avascular necrosis
1/24/2020 DR SIAMUNYANGA BRIGHT 21

22. Manifestations
• Acute Chest Syndrome
– Fever
– Tachypnea
– Chest pain
– Hypoxia
– Hypotension
– X-ray findings
1/24/2020 DR SIAMUNYANGA BRIGHT 22

23. Manifestations
• Splenic sequestration
– Large amounts of blood pools in spleen
• Splenic enlargement
• Circulatory collapse
– Reason unknown
– May follow febrile illness
• Aplastic episodes- may follow infection with
parvovirus B 19
1/24/2020 DR SIAMUNYANGA BRIGHT 23

24. Manifestations
• Cardiomegaly
• Gallstones
• Body habitus
– Underweight
– Delayed puberty
1/24/2020 DR SIAMUNYANGA BRIGHT 24

25. PRECIPTATING FACTORS FOR VASOCCLUSIVE
CRISIS
• physical stress,
• infection ,
• dehydration,
• hypoxia ,
• exposure to cold,
• acidosis
1/24/2020 DR SIAMUNYANGA BRIGHT 25

26. Approach
• Laboratory
– Normocytic anemia- Hgb 5-9 mg/dL
– Peripheral smear
• Target cells
• Poikilocytes
• Sickled cells
• Howell Jolly bodies
– Leukocytosis with neutrophil predominance
– Thrombocytosis
– X-ray- expanded marrow spaces, osteoporosis
1/24/2020 DR SIAMUNYANGA BRIGHT 26

27. Approach
• History
– Pain symptoms
• Recognition of specific processes
– Acute chest syndrome
– Cholecystitis
– Splenic seqestration
– Priapism
– Neurological changes
1/24/2020 DR SIAMUNYANGA BRIGHT 27

28. Approach
• Physical examination
– General: fussiness, irritability, poor feeding
– icterus, pallor, maxillary hyperplasia, Frontal
bossing(due to extramedullary erythropoiesis)
– Vital signs
– Neurological
– Cardiac: murmur
– Respiratory: asymmetry of breath sounds
1/24/2020 DR SIAMUNYANGA BRIGHT 28

29. Approach
• Physical examination
–Abdomen: assess for spleen, Murphy’s
sign
–GU: priapism ( prolonged
,painful,purposless,penile erection)
–Extremities: edema, inflammation
1/24/2020 DR SIAMUNYANGA BRIGHT 29

30. Frontal bossing
1/24/2020 DR SIAMUNYANGA BRIGHT 30

31. Approach
• Work-up
– Sickling/solubility test for screening
– HB electrophoresis for confirmation
– FBC, reticulocytes,
– peripheral smear
– If febrile, blood culture
– If lung findings, chest x-ray, blood gas
– If abdominal pain, liver enzymes, UA, abdominal
u.trasound
– Consider x-ray of extremities
– Head CT if neurological changes
1/24/2020 DR SIAMUNYANGA BRIGHT 31

32. Treatment
• ABCs
• Hydration- 1.5 times maintenance
• Analgesia
– ibuprofen
– Acetaminophen
– Opiates e.g. Morphine
• Treat the precipitating factor,eg give Antibiotics for
infection
1/24/2020 DR SIAMUNYANGA BRIGHT 32

33. Treatment
• For respiratory distress
– Antibiotic coverage
– Supplemental oxygen
– Partial exchange transfusion
• For splenic sequestration
– Repletion of intravascular volume
– Severe anemia, transfuse
1/24/2020 DR SIAMUNYANGA BRIGHT 33

34. Treatment
• For suspicion of stroke
– Exchange transfusion
• For priapism
– Analgesia, hydration
– Partial exchange transfusion
1/24/2020 DR SIAMUNYANGA BRIGHT 34

35. Treatment
• Outpatient
– Vaccinations
• Pneumococcal, meningococcal, influenza vaccines
– Penicillin prophylaxis
– Folic acid therapy
– Hydroxyurea (converts HbA to HbF)
Review regularly with FBC
– Malaria prophylaxis- Deltaprim once weekly
• Consideration for BMT for severe cases
1/24/2020 DR SIAMUNYANGA BRIGHT 35

36. Treatment cont..
• Anaemia transfusion with packed cells when Hb falls
below 5 gm/dl
• In sequestration crisis blood transfusion and
splenectomy with first episode
Allogeneic Stem Cell Transplantation
• Only Therapy Offering Curative Potential for sickle cell
disease
1/24/2020 DR SIAMUNYANGA BRIGHT 36

37. GENETIC COUNSELLING
• Who should receive counseling?
• -Parents of newborns with sickle disorders or traits
• -Pregnant women/ prenatal counseling
• What is the purpose of counseling?
• -Education
• -Informed decision-making
• Content should include:
• -Genetic basis, chances of disease or trait (potential
pregnancy outcome), disease-relatedhealth
problems, variability/unpredictabilityof disease, family
planning, average life span
1/24/2020 DR SIAMUNYANGA BRIGHT 37

38. Complications
• Anemia/Jaundice
• Brain Damage/Stroke
• Kidney failure
• Decreased lung function
• Eye disease (bleeding,
retinal detachment)
• Leg ulcers
• Chronic pain
managetmen
• Osteomyelitis
• Avascular necrosis of the
neck of the femur
• Dactylitis
• Arthritis
• Chronic leg ulcer
• Gall stones
• CVA
• Meningitis
• Priapism
1/24/2020 DR SIAMUNYANGA BRIGHT 38

39. THANK YOU
1/24/2020 DR SIAMUNYANGA BRIGHT 39