3. INTRODUCTION
• Sickle cell disease or anemia is an autosomal recessive genetic blood
disorder characterized by red blood cells that assume an abnormal
rigid sickle cell under reduced oxygen tension.
4. Definitions
• Sickle cell disease: Inheritance of two abnormal genes coding for haemoglobin and one
of which codes for haemoglobin S (genotypes SS, SC, SD, S- thalassaemia, S-
thalassaemia, S-HPFH)
• Sickle cell anaemia: Inheritance of two abnormal genes both of which code for
haemoglobin S (homozygous for haemoglobin S-genotype SS)
• Sickle cell trait: Inheritance of one abnormal gene coding for haemoglobin S
(hemizygous for haemoglobin S-genotype AS)
5. Pathophysiology
• Sickle cell anemia is caused by a point mutation, at position 6 of the
β-globin chain of hemoglobin, causing the hydrophilic amino acid
glutamic acid to be replaced with the hydrophobic amino acid valine.
• Red cells typically live for 90 -120 days but sickle cells only survive for
10 -20 days
6.
7. • Globin gene (Sixth codon)
GAG GTG
Glutamic acid Valine
• Sickle haemoglobin forms polymers when deoxygenated
• Deoxygenation induces potassium efflux, increasing cell density and the tendency of
haemoglobin S to polymerize
• Vaso-occlusion is initiated and sustained by interactions among sickle cells, endothelial cells and
plasma constituents
9. Clinical features
Haemolysis Vaso-occlusion
Anemia
Jaundice
Gallstones
Cardiomegaly : CHF
Leg ulcers
Marrow hyperplasia
Poor physical
development
Delayed maturation
Subjective symptoms
Painful crisis of bone,
muscle, abdomen
psychological dysfunction
Acute chest syndrome
Strokes
Eye damage
Functional hyposplenism
and autosplenectomy
susceptibility to infection
Chronic organ failure
10. Clinical features
Haematology Crises Organ dysfunction
Anaemia
Positive sickling test
Reticulocytosis
Neutrophilia
Increased platelets
P/smear
increased
polychromasia
nucleated RBCs
target cells
ESR low
Hb Electrophoresis
diagnostic SS pattern
Vaso-
occlusive
Sequestratio
n
Aplastic
crisis
Hyperhaemo
lytic
CNS
Heart
Lungs
Kidney
Liver & biliary
Bones
Eyes
Ears
Adenotonsillar
hypertrophy
Skin
Growth & development
Delayed height & weight
Delayed sexual maturation
Functional hyposplenism
Splenomegaly in early childhood
Progressive fibrosis
Reduced splenic activity
Howell-jolly bodies on PS
Increased risk of infection
11. Diagnosis
In utero
- Restriction endonuclease analysis of fetal fibroblast DNA
Amniocentesis
Chorionic villus biopsy
Neonatal period
- Electrophoresis
- PCR
Cord blood sample or DBS
Older children
- Electrophoresis
12. Health Care Maintenance
Comprehensive care
Genetic counseling -Preventive care
-Routine regular follow up
-Parent education
-Immunization
-Penicillin prophylaxis
-Nutritional counseling & FA
13. Acute vaso-occlusive event
Introduction
Top cause of hospital visit
Mx in childhood affects
ability to cope as
adolescent and adult
Barriers to effective Mx
limited knowledge of SCA
inadequate pain
assessment
biases against opioid use
Pain syndromes in SCA
Acute pain syndrome
Acute chest syndrome
Cholecystitis
Hand-foot syndrome
Painful episodes
Priapism
Right upper quadrant syndrome
Splenic sequestration
Chronic pain syndrome
Arthritis
Arhropathy
Avascular necrosis
Leg ulcers
Vertebral body collapse
Types of Pain
Acute pain - lasts hours to
a few days
Chronic pain - lasts 3 to 6
months Mixed pain - acute
superimposed on
chronic pain
14. Acute Pain Management
Assessment of
pain
Goals of assessment
1 To characterize pain and
related experiences
2 Provide basis for
therapeutic decisions
3 Document efficacy of
pain control
Rapid assessment of acute
pain
Comprehensive assessment
for chronic pain
Use of assessment
instruments
“Faces’ Pain” intensity scale
Visual analog scale
Multidimensional scales
Diary recall
Numeric pain scale in adults
15. Management of Pain crisis in SCA
Assessment and Intravenous Fluids
• Begin hydration
• 1.5 X maintenance or 2250 ml/m2/day
• 5% DNS
• Assess for cause of pain & complications
• Assess pain intensity
• Analgesic ℞
Drug management for pain
• Severe pain
• - Morphine 0.15 mg/kg/dose po/sc q3h
• Moderate pain
• - Oxycodone 5-10 mg/dose po q4h
• - Methadone 0.15 mg/kg/dose po q6h
• Mild pain
• - Ibuprofen
• - Acetaminophen 1.5 mg/m2/day po q4h
• - Codeine 0.75 mg/kg/dose po q4h
• Blood transfusion for refractory crisis
16. Acute Chest Syndrome
Investigation
s
Chest Xray
Blood count, reticulocyte
count
Blood culture, sputum if
possible
Arterial blood gases
mycoplasma titer
ECG
Viral studies
Treatment Recommendations
Oxygen
- hypoxemic patients
- nasally at 2 L/min
Simple transfusion
Antibiotics
- febrile and severely ill pts
- iv broad spectrum
- cefuroxime 100-500
mg/kg/day
- erythromycin to cover
mycoplasm
Pain control
18. Splenic Sequestration Crisis
Uncommon but may be rapidly fatal
Occurs between 5-24 months of
age
Abdominal discomfort or pain of
sudden onset
Accompanied by nausea and
vomiting
Splenomegaly
Precipitous drop in Hb, followed by
hypovolemic shock and death
Early education to parents
Transfuse to Hb 9-10 g/dl
Life threatening episode
- chronic transfusion
program or
splenectomy shortly after
- below 2 years chronic
transfusion to keep Hb S <
30% ; splenectomy
considered after age 2
years
Introduction Management
19. Fever & Infection
1. Physical examination
2. Laboratory evaluation
- Blood count
- Blood culture
- Chest Xray
- Urinalysis, culture & sensitivity
- mycoplasma titer
- Stool culture if diarrhea present
- Lumber puncture in patients < 1 yr
- Evaluate for osteomyelitis
3. Admit to hospital if < 5yrs & temp >38℃
4. Cover for streptococcus pneumoniae and Hemophilus influenzae
5. Discharge after 72 hrs if afebrile on oral antibiotics
6. Review within 1 week of discharge
20. Follow up
• Daily Folic acid for life
• Antimalarial prophylaxis
• Advise on keeping warm
• Drinking lots of fluid
• Nutrition
• Early health seeking behaviour
