Sickle cell disease is a genetic blood disorder caused by a mutation in the beta-globin gene. This mutation causes red blood cells to become sickle shaped and leads to anemia, pain crises, and organ damage. The disease is inherited in an autosomal recessive pattern and is most common in those with ancestry from sub-Saharan Africa, India, Saudi Arabia, and Mediterranean countries. Management involves staying hydrated, treating infections, managing pain, and potentially receiving blood transfusions or hydroxyurea therapy to reduce complications. Lifelong monitoring of health and adherence to prophylactic treatments and immunizations is important for sickle cell patients.

1. Sickle cell anaemia
Dr Ategeka Gilbert

2. • SCD is a chronic haemolytic disorder that is marked by polymerisation
of haemoglobin molecules within red cells and hence deforming the
red cell into a sickle (or crescent) shape.
• Sickle cell disease (SCD) encompasses a group of hemoglobinopathies
characterized by amino acid substitutions in the beta globin chain.
• Inheritance of 2 abnormal genes responsible for formation of HB.

3. • One of the 2 abnormal genes are responsible for formation of HBS
• Patients have the sickle mutation plus a second beta globin gene mutation, the
combination of which causes clinical sickling.
• These include :
• Sickle cell anemia (homozygous sickle mutation),
• Sickle beta thalassemia,
• Hemoglobin SC disease, and others.
• It is inherited in an autosomal recessive fashion either in the homozygous state or
heterozygous state.

4. • Hemoglobin S (HbS) results from the substitution of a valine for
glutamic acid as the sixth amino acid of the beta-globin chain, which
produces a hemoglobin tetramer (alpha2/betaS2) that is poorly
soluble when deoxygenated
Sickle Cell Trait
• If the other beta globin gene is normal.
• It is a benign carrier condition that is not a disease.

5. Sickle cell anemia
• Sickle cell anemia (HbSS), homozygous HbSS, occurs when both β-
globin alleles have the sickle cell mutation (βs).
• NB: both parents contribute mutated globin chain

6. Sickle cell disease is inherited in an autosomal
recessive pattern.

7. Structure of normal RBC and Sickle cells

8. Epidemiology
• SCD is one of the most common genetic diseases worldwide. Its highest
prevalence is in Middle East, Mediterranean regions, Southeast Asia, and
sub-Saharan Africa
• About 5–7% of the global population carries an abnormal haemoglobin
gene.
• The prevalence of sickle cell trait ranges between 10 and 45% in various
parts of sub-Saharan Africa
• Uganda, 2016 Prevalence SC trait at 13.3% and SC disease at 0.7%. Ndeezi
et al, 2016)
• Prevalence of ACS in SCA with fever found at 22.7%(256 children)- (Ochaya,
Hume, Bwanga, Tumwine)

9. Haemoglobin types
• Embronic HB – present upto 6/52 gestation.
• Gower -1
• Gower-2
• Portland
• Feotal HB- predominates thru pregnancy. At term 70-80%
• Haemoglobin F (apha 2 and Gamma 2 chains)
• Adult Hb - reaches adult level at 12 months post natally
• HbA (2 alpha and 2 betta)
• HbA2 (2 alpha and 2 sigmoid)

10. Pathophysiology
• SCA (HbSS), homozygous HbSS,
• occurs when both β-globin alleles have the sickle cell mutation (βs).
• HbS is typically as high as 90% of the total hemoglobin
• SCD
• HbS is 35-40% of all hemoglobin.
• heterozygotes where one β-globin allele includes the sickle cell mutation and the
2nd β-globin allele includes a gene mutation other than the sickle cell mutation, such
as HbC, β-thalassemia, HbD, and HbOArab

11. • In the absence of globin-chain mutations, Hb molecules do not interact
with one another.
• The presence of HbS results in a conformational change in the Hb tetramer,
• In the deoxygenated state, HbS molecules interact with each other, forming
rigid polymers that give the RBC its characteristic “sickled” shape.

12. • Sickled cells adhere to endothelial cells
• Endothelial factors increase vasoconstriction
• Blood flow reduces and promotes vaso-occlusion
• “Vicious cycle” with decreased blood flow, hypoxemia / acidosis,
increased sickling
• Some cells become irreversibly sickled

13. FACTORS THAT INCREASE HgbS POLYMERIZATION
• Decreased oxygen
• Increased intracellular hemoglobin S concentration (SS > SC, S-
thal)
• Increased 2,3-DPG
• Decreased pH
• Slowed transit time through the circulation
• Endothelial adhesion

14. FACTORS THAT DECREASE HgbS POLYMERIZATION
• Lower concentration of HbS (compound heterozygosity for
α-thal)
• Increased HbF levels
• Genetic basis
• Hydroxyurea

15. Clinical Features of Sickle Cell Anemia
• Painful episodes
• Pneumococcal disease
(pneumonia, meningitis,
osteomyelitis)
• Acute chest syndrome
• Splenic infarction
• Splenic sequestration
• Stroke
• Osteonecrosis
• Priapism
• Frontal bossing
• Leg ulcers
• Gallstones
• Renal abnormalities
• Osteopenia
• Nutritional deficiencies
• Placental insufficiency
• Pulmonary hypertension
• Proliferative Retinopathy
• Dactylitis
• Jaundice

16. Clinical features
• The hallmark of SCD is vasoocclusion : this acute , painful aspect of
SCD can be triggered by acidosis, hypoxia, dehydratation , infection
and fever and exposure to extreme cold.
• Painful episodes occur most often in the:
• long bones (limbs, ribs, sternum, vertebra and skull bones) ,
• lungs, liver, penis, eye, central nervous system and urinary tract.
• Acute chest syndrome describes new respiratory symptoms
and findings, often severe and progressive, in a patient with
sickle cell disease and new pulmonary infiltrate.

17. • Fever and Bacteraemia
• Fever in a child with sickle cell anemia is a medical emergency,
requiring prompt medical evaluation and delivery of antibiotics
because of the increased risk of bacterial infection and
subsequent high mortality rate
• Aplastic Crisis
• Human parvovirus B19 infection poses a unique threat for patients
with sickle cell disease because this infection results in temporary
red cell aplasia , limiting the production of reticulocytes and causing
profound anemia
• Any child with sickle cell disease, fever, and reticulocytopenia
should be presumed to have parvovirus B19 infection until
proven otherwise

18. • Splenic Sequestration
• Acute splenic sequestration is a life-threatening complication
occurring primarily in infants and young children with sickle cell
anemia.
• Splenic sequestration is associated with rapid spleen
enlargement causing left sided abdominal pain and Hb decline
of at least 2 g/dL from the patient’s baseline.
• Sequestration may lead to signs of hypovolemia as a result of
the trapping of blood in the spleen and profound anemia, with
total Hb falling below 3 g/dL.
• Sequestration may be triggered by fever, bacteremia, or viral
infections.

19. • Priapism
• Priapism, defined as an unwanted painful erection of the penis.
• Priapism occurs in 2 patterns: prolonged , lasting >4 hr, or
stuttering , with brief episodes that resolve spontaneously but
may occur in clusters and herald a prolonged event.
• Priapism in sickle cell disease represents a low-flow state
caused by venous stasis from RBC sickling in the corpora
cavernosa.
• Recurrent prolonged episodes of priapism are associated with
erectile dysfunction (impotence).

20. • Stroke
• blockage of blood flow or rupture of cerebral vessels.
• Prevalence of stroke in SCA in Uganda is 6.8% (Munube et al 2016).
• Ischemic stroke most common btn 2-9 yrs, accounts for 70-80% of
CVA in SCD.
• Haemorrhagic more common in older patients 20-29yrs-accounts for
1-3% of CVA in SCD.
• Transient ischemic attack (TIA) often precedes stroke

21. • Overt stroke is generally secondary to stenosis or occlusion of the
internal carotid or middle cerebral artery
• Strokes may be precipitated by Acute Chest Syndrome, parvovirus
infection, or other acute anemic events.
• Symptoms- Silent cerebral infarct
• Subtle behavioral changes
• Academic difficulties
• Symptoms- Acute Stroke
• Prolonged headaches
• Aphasia
• Hemiparesis
• Seizures
• Gait disturbances

22. Patients at high risk of stroke

23. Clinical features/complications

24. Diagnosis
• New born diagnosis
• Thin layer/ isoelectric focusing (IEF)
• high-performance liquid chromatography (HPLC)
• Sickling test – demonstrates a sickle shaped cell in microscope when
abnormal Hb is deprived of oxygen
• Solubility test – works on principle of abnormal HbS precipitating as a
result of its polymerization when exposed to low oxygen
concentration
• Peripheral blood film – sickled cells

25. Sicked cell of peripheral blood film

28. Management
• Sickle cell crises
• Predisposing factors include
• Dehydration
• Infection
• Strenuous exercises
• Extremities of temperatures
• Psychological stress
• Traumatic injury like surgery
• Drugs
• Sometimes cause is unknown

29. Types of SCD crises
• 1. Vaso-occlusive crisis (painful crisis)
• Acute chest syndrome -2nd most common
• s/S – tachypnoea or DIB, severe chest pain, fever, wheezing, nasal flaring, cough
• Major cause of death – 25% of death in PLSCD
• Haemolytic crisis – faster RBC destruction by the spleen
• Aplastic crisis – sudden reduction in RBC count. Due to Parvo B19 destroying RBC
precursors in the BM. s/s- excessive fatigue, tachycardia, excessive pallor, fever,
headache
• Sequestration crisis – spleen becomes clogged and congested with sickled RBC
which cant be freely filtered

30. Management :

31. Lab and investigations
• CBC
• Blood smear for malaria
• Urinalysis
• Blood culture
• RBS
• Grouping and x-match
• CXR
• Abdominal erect Xray , Uss
• Plain X-ray of the bones
• Brain CT
• LFT
• RFT
• NB: investigation depends on
the patient presentation

32. General management principles
• Proper adequate hydration
• Adequate pain control
• Treatment of infections
• Oxygen therapy if needed
• BT if needed
• treating any specific concerns as they present

33. • Fever
• <39 – oral antipyretics – PCM, Ibuprofen
• >39 – Iv/ IM antipyretics e.g iv PCM, im diclo
• Assess for the cause
• Pain relief
• analgesics depending on the pain scale

34. • Immediate hydration
• Maintenance fluid –using parkland formula. Fluid of choice is D5% or NS
• Acute chest syndrome
• Oxygen therapy
• Pain relief
• Hydration
• Antibiotic therapy
• BT
• Bronchodilators e.g salbutamol nebulization
• Advanced respiratory support

35. • Aplastic crisis
• BT at 20mls/kg of whole blood or 10ml/kg of PRBC
• Sequestration Crisis
• Blood transfusion
• Surgical removal if 2 or more sequestration crises in a period of 6 months
• Priapism
• Pain relief and hydration
• Minor – oral Etilefrine 25mg daily increased every 2 weeks . Max 100mg
• Conservative measures: ice pack on the penis and perineum, walking upstairs

36. • Major priapism
• Consult urologist for intracarvenosal phenyl ephedrine 0.5ml in 10-20mls of
NS @ 5 minutes up to 1 hour
• Stroke :
• Ensure ABC
• Hx, P/E , labs and CT
• Urgent BT
• Prevention - hydroxyurea

37. • Acute abdomen
• Should always be assessed by surgeon
• Causes
• Splenic infarction
• Mesenteric/colonic ischemia
• Renal /hepatic vein thrombosis
• Pulmonary inaction or pneumonia
• Hepatic infarction/ abscess/sequestration
• Intra-abdominal abscess
• NB: manage with general principles of analgesia, hydration, antibiotic and
reassurance .
• More specific mx as per cause

40. Health maintenance
• Non-pharmacological
• Taking enough fluids
• Avoiding strenuous exercises
• Avoiding extreme temperatures
• Eating balanced diet
• Avoiding stress
• Education on early features

41. • Pharmacological
• Folic acid – children 2.5mg daily
• Prophylactic antibiotics –
• 3months-2years- 125mg of Pen V twice daily
• 3-5 years- 250mg twice a day of Pen V
• Malaria prophylaxis – fansider
• Below 2 years- 1/2 a tablet monthly
• 2-5years- 1 table monthly
• Above 5 years- per body weight

42. • Immunisation
• - as per schedule
• PCV 13 boaster dose at 12 months
• Pneumococcal polysaccharide 23 valent vaccine is then started from 2 years
with boaster dose 3 years later
• Hydroxyurea
• Increases the concentration of foetal Hb thus reducing SCD crises
• Dose – start 15-20mg/kg once daily.

44. contraindications
• Pregnancy
• Kidney impairment or renal disease
• Liver disease
• PLT count <100,000cells/mm3
• Neutrophil count(not WBC) of less than 2500cells/mm3
• Hb>6g/dl
• Reticulocytes less than 95000cells/mm3
• Poor follow up
• Known Allergies to hydroxyurea

45. • Routine medical care
• Pt should be attached to a given SCD clinic or health centre .
• Should have CBC, LFTs, RFTs done every 6 months