1. Sickle cell anemia
Dr. Kalpana Malla
MD Pediatrics
Manipal Teaching Hospital
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2. Introduction:
• Abnormal haemoglobin (HbS) which has a
propensity for sickling and rapid haemolysis
under adverse conditions
• Valine, a hydrophobic amino acid replaces
glutamic, a hydrophilic amino acid at the sixth
amino acid position in the beta polypeptide
chain.

3. Genetics of Sickle Cell

4. EPIDEMIOLOGY
• Endemic malarial areas
• Central India, Sub-Saharan Africa,
Mediterranean, North Africa, Middle East
• South America, Carribean, US: African
descent…slave trade
• Incidence 1:625 in African Americans

6. The Proteins of Hemoglobin A
• There are 4 protein subunits of Hemoglobin A
Hemoglobin
A
Alpha Alpha Beta Beta
There will be different forms of Hemoglobin when there is a
mutation in the beta subunit.

7. A carrier for Sickle Cell Will
have…
•An S mutation
in one copy of Hemoglobin
the hemoglobin
beta gene.
•Half of the beta Alpha Alpha
Beta Beta S
subunits are
replaced with
Beta S.
•This person has
the Sickle Cell
trait.

8. When a person is a carrier, they will have:
25 % normal HbA 50 % HbS
25 % HbSS

9. Sickle Cell Disease:
•This results
HbSS
when both
copies of the Hemoglobin
hemoglobin beta
gene have an S
mutation. Alpha
Alpha Beta S Beta S
•All of this
person’s beta
subunits are
replaced by beta
S.

10. 1. It is Unknown why people with the Sickle Cell Trait are
RELATION TO MALARIA
resistant to Malaria, but there are several theories…
2. The carriers of Sickle Cell have some abnormal
Hemoglobin, and when they come in contact with the
Malaria parasite they become sickled. Then those cells
go through the spleen, which eliminates the cells
because of their sickle shape, so the Malaria would be
eliminated as well.
3. The Sickle Cell trait causes the malaria to stay in the
body for an extended period of time, so it is able to
build up a defense to it.

11. 3. Because oxygen concentration is low in the
spleen, and because infected cells often get
trapped in the spleen, it is possible that they
are destroyed in the spleen
• 4. The Malaria parasite produces an acid when
it is inside of the red blood cells. This causes
the red blood cells to polymerize, and the cells
will sickle. These sickled cells are then
destroyed when the blood cells go through the
spleen.

12. RELATION TO MALARIA
Sickle cell “trait” (heterozygote Hb AS) have:
• 1. lower levels of Pl. falciparum parasitemia
• 2. higher hemoglobin counts
• 3. less severe reinfections than normal ppl
Why?
• 1. confounding factors in these areas that confer immunity/
resistance:
Duffy chemokine factor
G6PD
HLA-B53, HLA-DRB1
• 2. actual mechanism not known

13. TYPES
• Hb SS (Homozygous S)- Sickle Cell Anemia
• Hb AS (Heterozygous S) - Sickle Cell Trait
• Sickle β0 Thalassemia (functions exactly like
Sickle Cell Anemia)
• Sickle β+ Thalassemia
• Hb SC ( mutation for Hb C occurs same site as
HbS. Instead of valine, lysine is exchanged for
glutamine)

14. SEVERITY OF DISEASE
Hb SS ≥ Sickle β 0 Thal >>
Hb SC >> Sickle β + Thal>> HbAS

15. PATHOPHYSIOLOGY
• Single base pair exchange
• Thymine for adenine in 6th
codon of β gene
• Encodes Valine instead of
Glutamine
• Charge at that site altered
• Allows polymerization of Hb
under hypoxia and acidosis
• Inc 2,3-DPG and dec pH
increases O2 affinity ->
hypoxia

16. PATHOPHYSIOLOGY (CONTD…)
• Amount of polymerisation is dependant upon the other Hb (extent of
homology with HbS)
• Copolymerization in this desc.order (S, C, D, O...so on and so forth)
• Polymerization -> RBC membrane alters-> sickling -> incr.adhesiveness ->
capillaries blocked -> local anoxia -> infarction of organs
• Infarction of liver, kidney, spleen, brain, bones, joints
• Thrombotic coagulopathy
• If resp infections -> hypoxia worsens -> more sickling
• Sickle cells seq in spleen. So splenomegaly
• Paradoxically spleen undergoes rptd infarction -> autosplenectomy
• Long standing hemolysis -> biliary pigment stones
• Long standidng hypoxia -> clubbing, leg ulcers, growth retardation
• Long standing anemia -> compensatory hyperactivity of BM

19. CLINICAL FEATURES
• Newborns: do not manifest as there is high HbF
• By 5-6mo: many have functional asplenia.
Hence bacterial sepsis
• By 5yr: 95 % functional asplenia
• Universally anemia and jaundice
• Thereafter CRISES EPISODES

20. CRISES EPISODES
• 1. HAND FOOT SYNDROME
• 2. ACUTE PAINFUL CRISIS
• 3. ACUTE CHEST SYNDROME
• 4. ACUTE SPLENIC SEQUESTRATION
• 5. STROKE

21. HAND FOOT SYNDROME
• Acute sickle dactylitis
• Painful, symmetric swelling of hand and feet
• Ischemic necrosis of small bones
• Blood supply choked off due to rapidly
expanding bone marrow
• Xray: extensive bone destr. and repair

22. ACUTE PAINFUL CRISIS
• Young children: mostly extremities
• Older patients: abdomen, back, chest
• Assoc with intercurrent illness
• Vaso occlusive event
• Abdominal organ infarctions

23. INFARCTS

24. ACUTE CHEST SYNDROME
• Pulmonary infarction
• Associated with pneumonia or microscopic fat
emboli from BM infarction
• Acute chest pain
• Hemopytsis
• Cyanosis
• May lead to death

25. ACUTE SPLENIC SEQUESTRATION
• In infants and young children (6mo-3yrs)
• Distinct and episodic event
• Foll acute febrile illness
• For unknown reasons large amounts of blood
become acutely pooled in spleen
• Massive enlargement of spleen
• Circulatory collapse

26. STROKE
• Catastrophic event
• >5yrs
• Hemiplegia
• 10% of patients affected
• 25-30% have occult strokes-
school performance affected
• Trancranial doppler studies

27. OTHER MANIFESTATIONS
RENAL
 Progressive deterioration
 Glomerular and tubular fibrosis
 Polyuria >5yrs
 Renal papillary necrosis -> hematuria
 Nephrotic syndrome
PRIAPISM
 Pooling of blood into corpora cavernosa obstructing
venous bloodflow

28. COMPLICATIONS
• Bacterial sepsis – H. influenzae, pneumococci
• Parvovirus B19 infection -> aplastic episodes
• Acute chest syndrome –> pulmonary infarction
• Chronic splenic sequestration
• Severe anemia
• Stroke -> hemiplegia
• Priapism -> impotence
• Chronic renal failure
• Skin ulcers
• Gall stones
• Avascular necrosis -> hip pain
• Retinopathy and Hyphema (more in HbSC d/s)
• Salmonella osteomyelitis
• UTI
• Growth retardation , delay in puberty
• Assoc Zn deficiency
• Sickle cell cardiomyopathy

29. BONE NECROSIS

30. INVESTIGATIONS
• Mild to moderate anemia (5-9gm/dl)
• Inc. retics
• Inc. TLC with sometimes Inc neutrophils
• Normal to inc. platelets
• Normal MCV (unless thalassemic Hb)
• PS: sickle cells, nucl RBCS, target cells, HJ bodies
• BM: hyperplastic marrow with erythroid predominance
• Xray:Osteoporosis, sclerosis of long bones
• Renal conc capacity decreased
• Hb electrophoresis
• Genetic / mutational analysis
• Prenatal diagnosis
• Transcranial doppler (TCD). If blood velocity >200cm/sec in brain, then
transfuse to keep Hb S <30%

31. PAPPENHEIMER BODIES

32. SICKLE THALASSEMIA
• Presentation is same as Hb SS (SCA) if Sickle β0
Thalassemia
• If Sickle β+ Thalassemia, then C/F are blunted
• Doubt if Hb electrophoresis shows HbSS
• But MCV <78fl or microcytosis in PS

33. SICKLE CELL TRAIT
• Assoc with α thalassemia
• Life span normal
• Complications rare
• Sudden death due to rigorous exercise
• Splenic infarcts at high altitude
• Hematuria
• Hyphema with IO bleed and blindness
• Renal medullary Ca predisposition

34. MANAGEMENT OF SCD
• General
• Prophylaxis
• Febrile episodes
• Analgesia
• Blood transfusion
• Drugs
• Bone marrow transplant
• Surgeries – splenectomy, cholecystectomy

35. GENERAL MANAGEMENT
• Vaccines
• Penicillin V prophylaxis
• Caretakers taught : temp, assess
illness, spleen, anemia, stroke…and bring to
hosp urgently
• Folic acid supplementation due to high red cell
turnover

36. MANAGEMENT OF FEBRILE EPISODES
• Hospitalise. Not OPD management <3yrs
• Look for occult bacteremia
• CBC, Blood culture, Urine culture, CXR
• Monitor for Acute splenic sequestration crisis
• Empirical Ceftriaxone (75-100mg/kg)

37. MANAGEMENT OF PAIN
• Paracetamol intially
• Later if relenteless pain : limited opiates –
codeine
• Wean off opiates in 3-4days
• Avoid masking of disease progression with
opiates
• >7-10 yr PCA (patient controlled analgesia)
pump
• Look for cause of pain

38. BLOOD TRANSFUSION
• Indications:
acute chest syndrome
stroke
severe anemia
acute splenic sequestration
• BT doesn’t reverse ischemic damage
• Can continue to have CVD and AVN
• Preferably give leuco-poor packed cell

39. DRUG THERAPY
 Hydroxyurea : 15-30 mg/kg/day
 Increases Hb F
BONE MARROW TRANSPLANT
 <16 yr with HLA matched sibling
 Only cure

40. Thank you
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Medical Post [ www.themedicalpost.net ]