Dr. KHALID SICKLE CELL

1. Sickle Cell Anaemia
Dr L Mukama

2. Learning Objectives
By the end of this session, students are expected to
be able to:
• Define sickle cell anaemia
• Explain the characteristics of red blood cells with
abnormal haemoglobin
• Describe the clinical presentation of sickle cell
anaemia
• Explain the management of a child with sickle
cell anaemia

3. Sickle cell disease (SCD) denotes all genotypes that
contain at least 1 sickle gene, in which haemoglobin
(Hb) S makes up at least half of the Hb present
In addition to homozygotic HbSS (sickle cell anaemia
[SCA]) in which only HbS is produced, at least 5 other
major genotypes are linked to the disease, including:
• HbS– β0 thalassemia- almost indistinguishable from
SCA phenotypically
• HbSC disease with intermediate clinical severity
• HbS/hereditary persistence of foetal Hb (S/HPHP) -
mild form or symptom free
• HbS/HbE syndrome - rare and generally mild clinical
course
• Other rare combinations
• SCA is the most severe and most common form

4. • Sickle cell anaemia originates from
inheritance of one copy of the sickle cell gene
from each parent, who may either be
heterozygous (Hb AS) or homozygous (Hb SS)
• Sickle cell trait is when one has normal adult
Hb A and an abnormal Hb S (i.e. heterozygous
[HbAS])
• These children are asymptomatic
• HbS is a result of the substitution of valine
for glutamic acid in position 6 of the beta (ß)
chain of Hb

5. • Note: HbAS offers some protection against falciparum
malaria. The infestation of the malaria
• plasmodium is halted by the sickling of the cell which it
infests.
• Characteristics of Red Blood Cells with Abnormal
Haemoglobin (HbSS)
• • Red blood cells (RBC) are abnormal and have short
life span of 8 to 20 days
• • Under low oxygen tension (that is when
deoxygenated)
• o Cells become elliptic (thus the name sickle cell), rigid,
sticky and fragile
• o Cells clump together and occlude small blood
capillaries

6. • Sickle-cell disease is an autosomal partially
recessive disorder of haemoglobin chains in red
blood cells

7. • When both parents have sickle-cell
trait (AS), they have a 25% chance (1
of 4) of a child's having sickle-cell
disease (SS).
• Since the gene is incompletely
recessive, sickle- cell trait (AS) can
produce a few sickled RBCs, not
enough to cause symptoms.

8. • The primary pathology springs from production of
abnormal haemoglobin (Hbs) which has a valine for
glutamic acid substitution at the sixth position of
beta globin chain.
Under low-oxygen conditions (e.g at high altitude),
the absence of a polar amino acid at position six
of the β-globin chain promotes the aggregation of
haemoglobin, which distorts red blood cells into a
sickle shape.

9. • Normal RBCs are quite elastic (flexible)
which allows the cells to deform to pass
through capillaries.
• Sickle RBCs are rigid to deform as a
consequence are unable to pass through a
narrow capillaries leading to vessel
occlusion and causes various pathologies.

11. Clinical Features of Sickle Cell
Anaemia
Buzz (10 minutes

12. • Although a diagnosis of the disease can be
made at birth, clinical abnormalities usually
do not occur before 6 months
• By the end of childhood, functional asplenia
due to repeated sickling of red cells and
ultimately infarction of splenic tissue results in
susceptibility to overwhelming infection with
encapsulated organisms such as Streptococcus
pneumoniae and Haemophilus influenzae

13. • The risk is decreased but still significant even
in the vaccinated population
• Subsequently, other organs are damaged
• Typical manifestations include recurrent pain
and progressive infarction

14. Age and Features of Sickle Cell
Anaemia
age features
0-4 months No features (due to presence of fetal Hb)
>4 months-1
year
Pallor, Dactylitis (hand and foot syndrome)
o Severely painful symmetrical swelling of the hands and feet
caused by infarctions of the small bones
• May be the initial manifestation, is most common in those < 2
years
• Jaundice, Recurrent infections, Splenomegaly
2-5 years Pallor, Jaundice, Recurrent infections, Hepatosplenomegaly
• Recurrent infections
>5 years Pallor, Jaundice, Bossing of the skull
• Long thin extremities, Autosplenectomy
• Adolescents may have delayed puberty

15. TYPES OF CRISES
1.Vaso-occlusive crisis
Most common hallmark of d’se due to: Obstruction of
blood vessel by rigid sickle
cells tissue hypoxia cell death
presents as pain & fever
In organs most common in:
abdomen (mesenteric), renal, cerebral, skeletal &
pulmonary capillaries
leads to clinical signs acute abd, haematuria, stroke,
bone pain & haemoptosis respectively.

16. 2.Aplastic crisis
-Depression of erythropoiesis generally associated
with infection esp parvovirus. Then presents with
anaemia.
3.Splenic sequestration crisis
Sudden pooling of red cells in spleen, acute fall in Hb,
shock
(i.e Reticulocyte count, Hb )
NB:Repeated infarcts in the spleen leads in
progressive splenic hypofunction & atrophy by abt
5yrs of age.

17. 4. HAEMOLYTIC CRISIS
– There is accelerated haemolysis and increased
reticulocytes
– Increased haemolysis is contributed by the
friability of the RBC membrane
• ACUTE CHEST SYNDROME
– New pulmonary infiltrates with fever and
respiratory symptoms
– Is the most common cause of death in sickle cell
disease

18. Hypersplenism
• Hypersplenism is a clinical syndrome in which cytopenias
result when splenic function becomes excessive as the
spleen enlarges
• This has been attributed to the following four possible
mechanisms
o Excessive splenic phagocytic activity
o Splenic production of antibodies that results in the
destruction of hematopoietic cells
o Over activity of splenic function
o Splenic sequestration
• If results in recurrent severe anaemia necessitating
repeated blood transfusion, splenectomy may be indicated
(refer to hospita

19. What precipitate Intravascular sickling crises?
•Acute infections
•Hypoxia
•Shock
•Dehydration
•Acidosis
•Exposure to cold

20. DIAGNOSIS
• Hemoglobin electrophoresis: Definitive test along
with DNA analysis
• Screening test “sickledex” or “shakes” tests are not
recommended to establish a diognosis or carrier
status
Should not be used for screening in children less
than 12 months of age as a result of false –
negative results.

21. Hemoglobin electrophoresis

22. • FBP: Hemoglobin values vary depending on age and
SCD genotype
• Reticulocyte count: increased
• Peripheral Blood Smear-sickled forms, targets,
nucleated RBCs, and increased polychromasia are
common RBC findings
– sickle forms may be absent in transfused patients or in
patients with phenotypes other than SCD-SS
• Biochemistry:
»Elevated LDH,
»Elevated unconjugated bilirubin,
»Elevated AST.

24. DIAGNOSIS
Prior to the first transfusion in any sickle cell
patient, draw blood for a red-cell antigen profile
for future reference. This is because of the high
risk of alloimmunization in repeatedly transfused
patients.
Neuropsychological Testing: strongly
recommended for children with a history of
stroke, silent infarction, abnormal TCD, or
learning difficulties.

25. Treatment
• Patients with sickle cell disease need
continuous Prophylaxis, Treatment and
Education.
• The main objective is to prevent, manage and
control symptoms, and to try to limit the
frequency of crises.
• During a sickle crisis, certain specific
treatments may be necessary.

26. Vasocclusive pain crises •Give IV fluids and analgesics
Acute chest syndrome •IV anbiotics (ceftriaxone if possible)
•Transfusion often necessary
•Give oxygen, incentive spirometry,
bronchodilators
•IV fluids and analgesia
Splenic sequestration
crisis
•Transfusion usually required
•Consider splenectomy to reduce risk of
recurrence
Aplastic crises •Transfusion usually required
•Bone marrow usually recovers within 2-
14 days
Hemolytic crisis •Usually accompanies a pain crisis
Fever •Low threshold for broad-spectrum IV
antibiotics (ceftriaxone if possible)

27. Mgt of VOC Pain Crises
• This should include aggressive pain
management with age-appropriate patient-
controlledanalgesia.
– PCM and Aspirin (over 12yrs)
– Others: Opioids (morphine or hydromorphone),
nonsteroidal anti-inflammatory agents (ibuprofen
or ketorolac), hydration, physical therapy, and
ancillary therapies such as relaxation or guided
imagery

28. Mgt of Acute Chest Syndrome
• The treatment for ACS includes broad-spectrum
antibiotics, including cephalosporin and macrolide
-Ampicillin, Gentamycin, Ceftriaxone
• In Addition: Oxygen, hydration,incentive spirometry,
and early intervention with simple transfusion
therapy for associated hypoxia or a hematocrit less
than 18% (0.18)

29. Mgt of Pneumococcal Infection
• Outpatient management of fever in children
who have SCD and low-risk parameters based
on age, degree of fever, leukocyte count,
clinical presentation, and parental compliance
now is standard
• Ceftriaxone is the antibiotic of choice for 48-
hour outpatient therapy in such patients

30. Transfusion Therapy in SCD Patients
• Transfusion therapy frequently is used transiently in
SCD to treat acute manifestations of the disease,
such as aplastic crises, splenic sequestration, and
ACS.
• Transfusion also can be used chronically to prevent
stroke. BUT, it is also associated with iron overload,
alloimmunization, and potential infectious
complications

31. Hematopoietic Stem Cell Transplant in SCD
• The only cure for SCD today is hematopoietic stem
cell transplant (HSCT).This requires a human
leukocyte antigen-matched sibling donor.
• Indications for HSCT include stroke, positive TCD
result, and multiple ACS or VOC episodes
• HSCT should be performed early, before end-organ
complications such as ironoverload or chronic
pulmonary disease occur

32. Additional Treatments :
1. Drug rehabilitation and counseling for psychological
complications
2. Hip replacement for avascular necrosis of the hip.
3. Irrigation or surgery for priapism.
4. Wound care, zinc oxide, or surgery for leg ulcers
5. Dialysis or kidney transplant for kidney disease
6. Transcranial Dopler scan of detecting risk of CVA
from 3yrs of age.

33. Management – Prophylaxis
Malaria : primaquine and other drugs in non immune and travellers
used
Folic Acid : Folic acid 5mg PO OD
Vit B complex
Hydroxylurea (hydroxycarbamide): prevention of acute chest
syndrome and reduce frequency of painful episodes and mortality.
Increases synthesis of HbF which inhibits polymerization of HbS.
Pnuemoccocal prophylaxis (Streptococcal pnuemoniae and H.
Influenza) by use of Penicillin V (Erythromycin for those allergic)

34. Management- Vaccinations
• Hepatitis B Vaccine
• H. Influenza Vaccine – recommended in all
children but more so in children with SCD as
infection can be fatal.
• Pneumovax (polysaccharide antigen) at 2yrs of
age (24-27months) and then every 5yrs.

35. • Prevention of Crises and Management
– Mothers taught
• How to Palpate and monitor spleen
• How to detect Pallor
• How to detect Jaundice
• Importance of Maintaining good hydration

36. COMPLICATIONS OF SCD

37. Destruction of
sickle cells
Clumping of
sickle RBCs
Concentration of
sickle cells in spleen
Proliferation
Of marrow
Anaemia
Impaired
mental
function
Towering
of skull
Weakness
Enlargement
of spleen
Fibrosis of
spleen
Impaired blood
supply to organs
Damage
to heart
muscle
Damage
To
lungs
Damage
To
Muscle
joints
Brain
damage
Kidney
damage
Heart failure
pneumonia
rheumatism
paralysis
Renal failure

39. ACUTE COMPLICATION
• PAINFUL EPISODES: occur suddenly, anywhere on
the body
• DACTYLITIS: painful swelling of hands and feet
• BACTERIAL INFECTIONS: sepsis and meningitis.
Especially Strep. pneumoniae & salmonella
• ACUTE CHEST SYNDROME: presents as pneumonia
• NEUROLOGIC: can range from stroke to TIA

40. • ACUTE SPLENIC SEQUESTRATION: spleen increases
in size HB decreases and reticulocyte count
• APLASTIC EPISODES: decreased RBC production
usually due to infection with pasrvovirus
• CHOLECYSTITIS: risk increases after age of 10years
• PRIAPISM: in males of any age

41. CHRONIC
• Delayed linear growth and puberty
• Cholelithiasis
• Retinopathy
• Neurologic sequel of stroke
• Hypersplenism
• Avascular necrosis
• Nephrotic syndrome
• Acute glomerulonephritis
• Pulmonary function abnormalities
• Primary nocturnal enuresis

42. PROGNOSIS
• LIFE EXPECTANCY:
• SCD-SS: 42-48
• SCD-SC: 60-68
• Penicillin prophylaxis and hydroxylurea has
increased life expectancy