Unit 5 Sickle cell-3.pdf

Eden University
UNIT 5 (Diseases of Blood)
Sickle Cell
2,2 Pediatrics Clinical Medicine
Dr. D.Nyirongo MD
UNZA (BSc.HB, MBChB, DTM)

DEFINITIONS
• Sickle Cell Anaemia (SCA) is a homozygous Hemoglobinopathy
characterized by chronic hemolytic anaemia that results from the
inheritance of two mutated β-globin genes coding for hemoglobin S
(Hb SS).
• Sickle Cell Disease (SCD) A heterozygous Hemoglobinopathy
characterized a group of diseases that result from the inheritance of
two mutated β-globin genes, one of which is HbS and the other gene
is either Hb S or other Hb variants such as Hb C, Hb β-thalassemia, Hb
D, and Hb O Arab.
• Sickle cell trait (Hb AS) rarely produces disease and this form protects
against death from endemic Plasmodium falciparum malaria infection
Dr. D. Nyirongo MD 28th July 2023 2

Sickle cell
• NOTE: In sickle cell Anemia, this change encodes valine instead
of glutamine in the 6th position in the β-globin molecule
• In sickle cell anemia, Hb S is commonly as high as 90% of the
total hemoglobin.
• In sickle cell disease, Hb S is >50% of the total hemoglobin.
• The mutant gene is inherited in an autosomal recessive
manner

Inheritance of Sickle Cell Anemia
• If one parent has sickle cell
anaemia (HbSS) and the other
is completely unaffected
(HbAA) then all the children will
have sickle cell trait.
• None will have sickle cell
anemia.
• The parent who has sickle cell
anemia (HbSS) can only pass the
sickle hemoglobin gene to each
of their children.

Inheritance of Sickle Cell Anemia
• If both parents have sickle cell
trait (HbAS) there is a one in four
(25%) chance that any given
child could be born with sickle
cell anemia.
• There is also a one in four chance
that any given child could be
completely unaffected.
• There is a one in two (50%)
chance that any given child will
get the sickle cell trait.

Pathophysiology of anemia in SCA
The major pathophysiologic mechanisms in SCA that cause
the signs, symptoms and complications are:
• Hb S polymerizes in conditions of low oxygen tension
leading to distortion of RBC into a crescent ‘sickle’
shape
• Sickle RBCs are less deformable and obstruct the
microcirculation (vaso-occlusion) resulting in tissue
hypoxia
• Sickle RBC undergo intravascular and extravascular
hemolysis and have a lifespan of only 10-20 days as
compared to 120 days of normal RBCs.
• There is adhesion of sickle RBCs and leukocytes to
activated vascular endothelium leading to
vasoconstriction

Prevalence of symptoms at age
• Six month of age - 6%
• Twelve months of age - 32%
• Two years of age - 61%
• Six years of age - 92%
• eight years of age - 96%

CLINICAL FEATURES
History of
• Swelling and pain of hand and feet i.e.
dactylitis (hand and foot syndrome)
especially in infancy
• Recurrent painful episodes in limbs,
abdomen, back, chest
• In infancy, may present as unexplained
episodes of excessive crying
• Recurrent or persistent jaundice
• Pallor or anaemia that may require
blood transfusions
On examination, may have/be
• small for age
• pallor
• Jaundice
• frontal and parietal bossing
May present in a sickle crises
• Vaso-occlusive crisis (has 5 types)
 Painful crisis
 Dactylitis
 Acute chest syndrome
 Acute CNS event
 Priapism
• Hemolytic crisis
• Sequestration crisis
• Aplastic crisis

SICKLE CELL CRISES
[1] VASO-OCCLUSIVE CRISIS (VOC)
• Vaso-occlusive crises occur due
to disruption of blood flow in
the microvasculature by sickle
cells
• Resulting in tissue ischemia,
temporally loss of function
which may become permanent
and pain
Precipitating Factors for VOC
These include:-
• Infection,
• Dehydration,
• Exposure to cold,
• Emotional and physical stress,
• Hypoxia especially in high
altitude

SICKLE CELL CRISES
Vaso-occlusive crises include The following Types
i. Painful crisis (most common)
ii. Priapism (prolonged, painful erection
of the penis)
iii. Acute chest syndrome
iv. Dactylitis (tender, erythematous and
edematous hands and feet)
v. Stroke (CVA) and
Mnemonic to remember the VOCs= PPADS
NOTE: Discuss how each VOC is Managed?
(iii) ACUTE CHEST SYNDROME
• It is defined a new pulmonary infiltrate on chest
radiograph in the presence of one or more of the
following: fever, tachypnea, dyspnea, hypoxia and
chest pain
• In most cases, there is no identifiable cause, but
in some cases, it may be caused by
Infections – Chlamydia pneumoniae, viral
infections, Mycoplasma pneumoniae
Pulmonary infarctions (from sickled cells)
Fat embolism (from bone marrow infarctions)

SICKLE CELL CRISES
[2] HAEMOLYTIC CRISIS
• >2g/dL drop in Hb from baseline with
reticulocytosis and raised
unconjugated bilirubin
• May result due to painful crises or
infection
• Transfuse with packed cells if Hb fall
to <5g/dL
[3] SEQUESTRATION CRISIS
• It is the sudden enlargement of the
spleen along with > 2 g/dL decrease in
Hb from baseline with reticulocytosis.
• This is an emergency! Because It
occurs rapidly and can result in sudden
circulatory collapse
• It is a common cause of death in
infancy
Clinical Presentation
• Severe pallor with acutely enlarged
spleen
• Hypovolemic shock
• Severe anaemia, thrombocytopenia
and normal reticulocyte count

[4] APLASTIC CRISIS
This is a Transient red cell aplasia commonly caused by parvovirus B19
• Parvovirus B19 has a predilection for young erythroblasts in bone marrow
which are plentiful in hemolytic anemias
• Infection limits the production of reticulocytes
• Infection usually is self-limited
• May present with fever, upper respiratory tract symptoms, fatigue, pallor.
• >2g/dL drop in Hb from baseline, leukopenia with reticulocytopenia.
• The reticulocytopenia may last 7 to 10 days

Long term Complications
• Functional asplenia due to
autosplenectomy
• Increased risk of serious bacterial
infections
• Faltering growth
• Osteomyelitis
• CNS conditions
• Strokes or TIA, convulsions, sensory
hearing loss
• Priapism
• Delayed sexual maturation
• Cholelithiasis
• Renal disease (Gross hematuria,
papillary necrosis, nephrotic syndrome,
renal infarction, hyposthenuria,
pyelonephritis, renal medullary
carcinoma)
• Chronic lung disease (pulmonary
hypertension)
• Congestive heart failure
• Proliferative retinopathy
• Leg ulcers
• Avascular necrosis of the femoral or
humeral heads
• Chronic pain syndrome

Management (Investigations)
1. Clinical
2. Laboratory
• FBC
• Peripheral Blood Smear reviews Sickle cells,
target cells, Howell-jolly bodies
• Reticulocyte count
• X-ray of the skull (hair on endplate
appearance. Frontal bossing)
• Sickling test, solubility test and sickle scan
All three are screening tests, they do not
distinguish between SCD and sickle cell trait
and must be followed up by a more specific
diagnostic tests eg Hb electrophoresis and
HPLC
1. Sickling test – observation of sickled RBCs
on a microscope slide when drops of blood
are exposed to sodium metabisulphite which
causes low oxygen tension
2. Solubility test – observation of turbidity
when drops of blood are mixed with sodium
dithionate in a test tube, insoluble HbS
remains turbid. While HbA which is soluble
in the solution turns clear
3. sickle scan- Detects Hb A, C and S
(quantitatively)
• Hb electrophoresis (measures number,
and type of both normal and abnormal Hb)
• High-performance liquid chromatography
(HPLC) (detects the type of hemoglobin
present)

Management (Treatment)
Mainstay treatment
 Improve Oxygenation and fluids (1.5 times maintenance fluid)
 Pain management (paracetamol->NSAID->Morphine=0.3mg/Kg 4
hourly) NEVER give fentanyl due to risk of seizures
 Vaccinate against encapsulated organisms
8 General treatment Principles
1. Folic acid
2. Malaria prophylaxis
3. Antibiotics
4. Avoid crisis precipitants
5. Regular hospital review
6. Counseling
7. Hydroxyurea
8. Blood Transfusion
(1) Folic acid 5mg daily
(2) Malaria prophylaxis with
Deltaprim (pyrimethamine and dapsone)
• <12kg 50mg once weekly PO
• >12kg, 100mg once weekly PO
Side effect: It can cause agranulocytosis
(3) Antibiotics (Oral penicillin daily)
• because of increased risk of bacterial infections
• Penicillin V until the age of 5 years
2 to 12 months 62.5mg BD
1 to 3 years 125mg BD, then
3 to 5 years 250mg BD. If allergic to pen V, give
erythromycin.

(4) Avoid crisis precipitants
• Precipitants are dehydration, cold, fever, hypoxia
• Advice as follows: hydrate enough, keep warm,
cool when hot, adequate ventilation
• when fever present to go to the clinic/hospital
quickly and not self-treat at home
(5) Regular hospital review
• Frequency of review is based on how patient is
doing
• Monthly reviews in infancy, 2-3 months in older
children or longer if stable
(6) Counseling
• Teach caregivers and patients about the
disease, role of medicines prescribed and
how to avoid VOC precipitants
• Teach caregivers of SCD children aged <3
years how to palpate for the spleen. After
teaching, observe them palpate to ensure
they do it correctly
• Advise to palpate every day when bathing the
child
• Advice to go to the hospital (not clinic) quickly
if spleen is noted

(7) Hydroxyurea
• Mechanisms of action (MOA)
Increases the production of fetal Hb (HbF).
Decrease red cell endothelial adhesion
Increase RBC water content making it
flexible and difficult to polymerize
Cause Nitric oxide release Vasodilatation
Decreases Neutrophil count
• o Indicated in stroke, recurrent painful VOC,
acute chest syndrome
• Dose is 10-15mg/kg once daily initially,
then increase every 12 weeks in steps of
2.5-5mg/kg ,max 35mg/kg daily)
(8) Blood transfusion
This is indicated in:-
• Severe anaemia, sequestration crisis, aplastic crisis,
acute chest syndrome, priapism, stroke
• Do not tansfuse to an Hb to >10g/dL to prevent
hyperviscosity which decreases oxygen delivery
Give packed cells: transfuse 11 times for 6 Months.
1st Month weekly=4 times
2nd & 3rd Month 2 weekly=4 times
Remaining 3 Months Once Monthly=3 times
Amount of Blood=(BW x Hb deficiency) x K
Where K=4 for packed cells
K=6 for whole blood

Transfusion therapy (Indications)
• Vaso-occlusive crisis
 Painful crisis
 Dactylitis
 Acute chest syndrome
 CVA (TCD ultrasound results of more than
200cm/s) or stroke
 Priapism
• Hemolytic crisis
• Sequestration crisis
• Aplastic crisis
• Perioperative
NOTE: Do not raise Hb > 10g/dL
Transfusion complications
• Alloimmunization
• Iron overload
• Infection

Causes of death
• Infection - 48%
• Stroke - 10%
• Complications of therapy - 7 %
• Splenic sequestration - 7 %
• Thromboembolism - 5%
• Renal failure - 4 %
• Pulmonary hypertension - 3 %

Unit 5 Sickle cell-3.pdf

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Unit 5 Sickle cell-3.pdf