SCD CPD

THE THREAT OF SICKLE CELL
DISEASE TO CHILD SURVIVAL
 Lecture delivered at the CPD of the MDCAN

OOUTH Chapter on 2nd July 2015
by
 D.M . Olanrewaju, FWACP, FRCP Edin
 Professor of Paediatrics, Olabisi Onabanjo

University, Ago-Iwoye, Nigeria.
Friday, August 21, 2015 1

SICKLE CELL DISEASE
 Sickle cell disease (SCD) consists of a
group of disorders characterised by the
presence of sickle haemoglobin. (HbS)
 Sickle Hb is caused by mutation in the gene
encoding the β chain of hemoglobin.
 Sickled rbcs were first observed in 1910 by
JB Herrick in a Black West Indian student.

Introduction
 HbS is the result of a single base-pair
change, thymine for adenine , at the
sixth codon of the beta gene. This
change encodes Valine instead of
glutamic acid in the sixth position on
the beta globin molecule.

Note!
 Sickle cell disease-
 Sickle cell anaemia-
 Sickle cell trait-

Haplotypes
 The different DNA structures
associated with the sickle gene are
identified by a pattern of restriction
enzyme sites, referred to as beta globin
haplotypes, which are assumed to
represent independent occurrences of
the sickle cell mutation and are named
after the places where first described.

 It has been documented that the Bs mutation
occurred on five major haplotypes and these
were named for the regions of Africa and
Asia where each was most prevalent. These
are:

Haplotypes
 1.Benin (BEN)-found in Nigeria
 2.Senegal (SEN)
 3.Bantu (BAN)
 4.Cameroon (CAM ) and
 5.Saudi Arabia/India (SAI)

INCIDENCE.
 HbS gene is prevalent in malaria-endemic regions
 Distribution is however world-wide, with the
greatest incidence in tropical Africa.
 It occurs in the USA, Middle East, India, the
Caribbean, South and Central America, Turkey
and throughout the Mediterranean region.
 2-3% of Nigerian newborns homozygous.
 Incidence in the general Nigerian population is
1:300.
 Frequency of the S gene in Nigeria…25%. Mode
of inheritance= autosomal recessive.
The Burden of a Disease
Global Burden of Sickle Cell Disease
1.How many people are affected?
2.What is the number of years of life lost due to premature
mortality?
3.What is the number of years lived with any short-term or
long-term disability?
4.What is the sum of years lost due to premature death and
years lived with disability (DALY)? Also defined as years of
healthy life lost.
5.What is the financial burden on individual, family,
community, country?

Burden of SCD
 Country sickle cell birth/yr
 Nigeria 91,011
 Dem Rep congo 39,743
 Tanzania 11,877
 Uganda 10,877
 Angola 9.017
 Cameroon 7.172
 Ghana 5.815
 Worldwide
Friday, August 21, 2015 total 305,773 12
How many people are born with SCD? Global Burden of Sickle
Cell Disease
Piel et al. 2013. Lancet 381:142–51 Estimated Newborns with AS
and SCD-SS 2010
Region AS SS %
Global 5,476,407 312,302 100
Americas 386,430 12,802 4.6
Arab-India 1,147,477 46,826 16.9
Eurasia 256,163 7,493 3.0
Southeast Asia 2,535 21 0.0
Sub-Saharan Africa 3,580,207 235,681 75.5

Newborns with SCD Increasing Globally
2010-2050 Estimated Newborns with
SCD-SS
Sickle Region 2010 2050 2010-2050

SS % SS % change
Global 305,773 100 404,190 100 +32.2
Americas 11,181 3.7 9,628 2.9 -13.9
Arab-India 47,264 15.5 36,540 12.0 -22.7
Eurasia 5,132 1.7 4,478 1.4 -12.7
Southeast Asia 7 0.0 8 0.0 +14.3
Sub-SAfrica 242,187 79.2 353,533 83.7 +46.0

Newborns with SCA increasing globally
Country 2010 2050 2010-2050
SS % SS % %change
Global 305773 100 404190 100 +32.2
1. Nigeria 91,011 29.8 140,837 34.8 +54.7

2. India 44,425 14.5 33,890 8.4 -23.7
3. Congo DR 39,743 13.0 44,663 11.1 +12.4
21. USA 2,842 0.93 3,379 0.83 +18.9
14. Ghana 5,815 1.90 6,855 1.70 +17.9

What happens to all those babies
with SCD?
It depends on where the baby was

born and lives. Contemporary
survival data are not widely
available, but there is ample
evidence that most children with
SCD in Africa suffer relentless
pain, experience numerous
infections and die before their 5th
birthday.
sickle-cell anemia contributes the equivalent of
5% of under 5 deaths on the African continent,
more than 9% of such deaths in West Africa,
and up to 16% of under-5 deaths in individual
West African countries

Mortality from cohort studies
 Jamaica...2. 5 per 100 PYO
 Tanzania....1.9 per 100 PYO
 USA......3 per 100 PYO (before pencillin p)

 ......0.13 per 100 PYO

CHILDREN WITH THE SICKLE TRAIT ARE
RELATIVELY RESISTANT TO MALARIA
 Just how this protection works is not

fully understood
 Malaria parasites that invade red blood
cells of individuals carrying the trait
die with the cells when the latter
assume the sickle shape and adhere to
the walls of the blood vessels.
 Sickle trait alters biochemical/immune
mech in the blood compromising p
PATHOGENESIS
 The hemoglobin molecule (made of alpha
and beta globin subunits) picks up oxygen
in the lungs and releases it when the red
cells reach peripheral tissues, such as the
muscles. Ordinarily, the hemoglobin
molecules exist as single, isolated units in
the red cell, whether they have oxygen
bound or not. Normal red cells maintain a
basic disc shape, whether they are
transporting oxygen or not.

 The picture is different with sickle
hemoglobin (Figure 1). Sickle hemoglobin
exists as isolated units in the red cells when
they have oxygen bound. When sickle
hemoglobin releases oxygen in the
peripheral tissues, however, the molecules
tend to stick together and form long chains
or polymers (polymerization). These rigid
polymers interact with the cell and cause it
to bend out of shape
Polymerized sickle hemoglobin does not form single
strands. Instead, the molecules group in long bundles of
14 strands each that twist in a regular fashion, much
like a braid (Figure 2)

 While most distorted cells are simply shaped
irregularly, a few have a cresent-like appearence
under the microscope. These cresent-like or
"sickle shaped" red cells gave the disorder its
name. When the red cells return to the lungs and
pick up oxygen again, the hemoglobin molecules
resume their solitary existence .
 A single red cell may traverse the circulation
four times in one minute. Sickle hemoglobin
undergoes repeated episodes of polymerization
and depolymerization (sickle—unsickle cycle).
This cyclic alteration in the state of the molecules
damages the hemoglobin and ultimately the red
cell
Friday, itself.
August 21, 2015 24
Diameter of RBC =7microns
Diameter of capillaries =3microns

Sickling occurs at the venous end of
capillaries while unsickling occurs at the
arterial end.
Initially there are series of sickle-unsickle
cycles .
Finally,the cells become irreversibly sickled.
 Sickle RBCs adhere to the endothelium
because of increased stickiness. The
endothelium participates in this process as
do neutrophils, which also express
increased levels of adhesive molecules.

 Sickle cells also adhere to macrophages.
This property may contribute to
erythrophagocytosis and the hemolytic
process. The microvascular perfusion at the
level of the prearterioles is influenced by
RBCs containing Hb S polymers. This
occurs at arterial oxygen saturation, before
any morphologic change is apparent.
 Two essential pathological processes arise from
sickling: haemolysis and vaso-occlusion The
pathological features of SCD relate to the
shortened life span of the sickled blood cells (16-
20 days in contrast to a lifespan of 120 days in
normal red cells) causing a haemolytic anaemia
 Large vessel damage is caused by repeated
endothelial damage by adherent sickle cells,
complicated by vasoconstriction and nitric oxide
deficiency. This mechanism is likely to be
responsible for complications such as pulmonary
hypertension and stroke. Small vessel occlusion is
caused directly by sickled cells. Vaso-occlusion
may cause acute episodes such as painful crisis or
more chronic damage such as avascular necrosis
of hips and renal failure.
 Vaso-occlusion appears to be a complex
event mediated by red cell and leukocyte
adhesion, inflammation, injury to the
endothelium, and activation of coagulation
pathways. Vaso-occlusion is the major
cause of morbidity and mortality in SCD,
with occlusion of blood vessels followed by
ischemia or infarction in various tissues,
leading ultimately to progressive end organ
damage.
The process of vaso-occlusion
 It was first thought that hemoglobin S
polymerization resulted in the entrapment of
sickled, poorly deformable erythrocytes that
mechanically blocked small caliber vessels. It
was later recognized that these damaged
erythrocytes alone are not sufficient to produce the
vaso-occlusion in larger vessels which can be
observed in both humans and in animal models.
End organ complications of SCD occur as a result
not only of small vessel disease but also in post-
capillary vessels and in arteries. This is
particularly evident from the increased risk of
cerebrovascular complications that tend to involve
large
Friday, cerebral
August 21, 2015 arterial vessels in patients with SCD31
 Damage similar to that seen in patients with
atherosclerotic vascular disease has been seen in
the large cerebral vessels of patients with SCD,
including intimal hyperplasia, and fibroblast and
smooth muscle proliferation. Endothelial damage
and activation due to interactions between
adherent sickle erythrocytes and the endothelium4
are therefore thought to contribute to the
vasculopathy involving small and large vessels in
SCD

Erythrocyte surface adhesion
receptors
 There are several cell surface receptors that
appear to be involved in mediating the
interaction between HbS erythrocytes and
the endothelium. These include: Lutheran
blood group antigen, also known as basal
cell adhesion molecule/Lu (BCAM/Lu,
CD239); integrin associated protein
(CD47); CD147; intercellular adhesion
molecule-4 (ICAM-4, ) , to mention a few.

Role of leukocytes in vaso-
occlusion
 Clinical observations that leukocytosis correlates
with poor outcome and increased severity of
disease in some patients suggest that leukocytes
play a role in the pathogenesis of SCD. A high
steady state leukocyte count is a risk factor for
acute chest syndrome, stroke, and mortality. In a
multicenter study of hydroxyurea in adults, the
clinical benefits correlated with a reduction in the
neutrophil count, even without the expected
increase in hemoglobin-F levels. In vitro studies
have also demonstrated that HbS erythrocytes bind
to neutrophils in a static adhesion
Role of platelets in vaso-occlusion
 There is evidence to suggest platelet involvement
in SCD pathogenesis. Circulating platelets in SCD
patients are abnormally activated during both
steady state and vaso-occlusive crisis. This can be
seen from increased levels of platelet contents
such as thrombospondin and IL-1 in the plasma, as
well as increased platelet P-selectin and von
Willebrand factor (vWF). Increased expression of
P-selectin is thought to be an initial step in the
development of vascular disease, since P-selectins
are involved in promoting platelet adhesion to
damaged vascular endothelium and initiating
thrombosis
Factors enhancing sickling.
 1.Hypoxia.
 2.Presence of WBC.
3 ” of Bacteria.
 4.Fever.
 5.Dehydration.
 6.Metabolic acidosis.
Role of free radicals in
pathophysiology.
 Free radical = molecule or molecular
fragment with single unpaired electrons.e.g.
OH-(hydroxyl), O2- (superoxide)
 They are aggressive and try to achieve
stability by attracting electrons from other
molecules. Said to be the most destructive
agent in nature. Responsible for organ and
tissue damage.
Free radicals…………………
 Generation of free radicals
Tissue damage
 Lipid peroxidation altered membrane
structure and function.
 Sickled RBCs have reduced vit E content
 Spontaneous O2 radical generation occurs in
SCD.

Free radicals…………………..
 Fe acts as a catalyst in the production
of the destructive hydroxyl radical.
Lipid peroxidation:
 RH +X-…………….R-+XH
 R-+O2 ……………..ROO-
 ROO-+RH………….R- +ROOH etc.
 Termination by antioxidants.

CLINICAL FEATURES
 Protective effect of HbF delays onset

of manifestations.

Clinical features…
 6mo to 2yrs
 Dactylitis. – due to ischaemic necrosis of
the small bones, believed to be caused by a
choking off of the blood supply as a result
of the rapidly enlarging bone marrow.
 Tender,warm,non-pitting swelling of dorsa
of hands and feet.—Hand-foot syndrome.
 Failure to thrive, anaemia, jaundice,
infections, crises.

Presentation after 2 years……
 Failure to thrive
 Anaemia, jaundice
 Infections
 Crises
 Sickle cell habitus….long, thin
limbs,protuberant abd, gnathopathy,
peculiar facies.
COMPLICATIONS OF SCD.
 Pathologic changes occur in all organs

as a result of the combined effects of
chronic hypoxia, recurrent infections,
and infarction

Musculo-skeletal system
 Osteomyelitis
 Bone infarction/osteonecrosis
 Pathological fractures,
 avascular necrosis,
 chronic leg ulcers,
 digital clubbing.

Avascular necrosis of femoral head

Hepato-biliary complications…
 Hepatomegaly/hepatic necrosis. The
latter is due to ischaemic damage to the
liver.
 Sickle-cell hepatopathy.
 Hepatic coma…..rare.
 Cirrhosis/haemosiderosis
 Cholelithiasis
 Choledocholithiasis
Genito-urinary complications...
 Enuresis/polyuria due to
hyposthenuria.
 Dilute urine favours bacterial growth.
 Pyelonephritis.
 Haematuria.
 Ischaemic damage to the kidneys.
……contd

Genito-urinary…….
 Progressive azotaemia/renal failure.

 Priapism.-
 Nephroticsyndrome.
 Renal medullary carcinoma.

Cardiovascular complications.
 Cardiomegaly.
 Ischaemic damage to the myocardium.
 Congestive cardiac failure.
 Cor pulmonale.

Respiratory complications….
 Pneumonia.
 Pulmonary infarction
 Pulmonary arterial hypertension
 Fat embolism.
 Hypoxaemia…due to intrapulmonary R-L
shunts, membrane diffusion defects, and a
shift of the dissociation curve to the
RIGHT.
 Restrictive impairment of ventilatory
function.

ACUTE CHEST SYNDROME
 The acute chest syndrome is similar to
a vaso-occlusive crisis in the lungs and
results from occlusion of the
microcirculation of the pulmonary bed.
The syndrome consists of progressive
respiratory distress and hypoxia, chest
pain, and cough accompanied by
infiltrates on a CXR.
 The aetiology is multifactorial and includes stasis,
hypoventilation, infection, fat embolization from
bone marrow necrosis and microthrombi in the
pulm circulation, all of which may be involved
singly or in combination. There is a massive
inflammatory response, a capillary leak may
develop , and there is progression to respiratory
failure. Management usually includes an
exchange transfusion, anti-inflammatory
therapy,antibiotics and respiratory support.

Obstructive sleep apnoea
 Common in SCD.
 May be due to tonsillar hypertrophy
 It may be associated with overnight hypoxia,
which may increase the frequency of voc and
neurological complications.
 Overnight sleep studies should be performed on
those who snore, have symptoms of daytime
somnolence, or who are hypoxic at rest.
 Full polysomnography may be necessary in some
cases. Those with abnormal sleep studies may be
considered for a trial of continuous positive
airway pressure b4 or in addition to a
tonsillectomy.
Pulmonary hypertension
 Peulmonary hypertension has been described in 5-
30% of adult pts with scd. It is thought to be due
to chronic haemolysis releasing free Hb which
leads to nitric oxide deficiency, causing acute and
chronic pulmonary vasoconstriction. Pts with PHT
are often asymptomatic even with severe disease,
and by the time they develop symptoms it may be
too late for effective treatment.
 Diagnosis of PHT is made by the finding of a
raised mean pulmonary arterial pressure of more
than 25mmHg at cardiac catheterisation.

NEUROLOGIC COMPLICATIONS
 Convulsions…may be due to
fever,meningitis, or CVA.
 CVA may lead to aphasia, spastic
hemiplegia…thrombotic/hemorrhagic.
 Incidence of CVA is low in
children….0.15% to 1.0%
 Risk factors for infarction….Prior TIA, low
steady state Hb, elevated BP, recent acute
chest syndrome. Contd.

Stroke
Most of these strokes are infarcts in the
distribution of the internal carotid artery
or the middle or anterior cerebral
arteries. The peak incidence is between
four and six years of age.
Although strokes usually occur without
warning, they are occasionally preceded
by severe headaches or deterioration of
school performance. The sudden
appearance of a limp in a child with
sickle cell disease warrants careful
evaluation for a neurologic cause.
 Strokes can be diagnosed by computed
tomography or magnetic resonance imaging
(MRI). Studies have recently shown that
"silent" lesions on MRI studies (even in the
absence of clinical signs) or high flow values on
transcranial Doppler ultrasound examinations
are associated with a high risk of stroke;
treatment of such findings may be warranted.
These imaging studies should be obtained and
read by personnel and physicians with specific
expertise in pediatric sickle cell disease.

Epilepsy
 Seizures occur in 10-15% of adult pts with
scd. This is 10x the incidence in the general
population. They are associated with
cerebrovascular disease and overt
infarction. Patients usually respond to
anticonvulsants.

Chronic headache
 This is very common in SCD and may be due to
migraine, benign intracranial hypertension
(perhaps as a consequence of venous sinus
thrombosis), hypertension or sleep apnoea as well
as tension.
 Intracranial hypertension is suggested by headache
occurring on waking, particularly if this occurs in
the middle of the night. The first episode of acute
severe headache or a significant change in the type
of headache should be evaluated as an emergency
in case this is a presentation of intracranial
haemorrhage or venous sinus thrombosis.

Ocular complications………..
 Dilatation/tortuosity of retinal vessels.
 Retinal haemorrhage.
 Vitreous haemorrhage—
 Glaucoma, due to blockage off
trabecular meshwork by blood clot
 Proliferative retinopathy.
 Retinal detachment
 Visual impairment.
Endocrinopathies………
Reduced growth hormone from

ant. Pituitary .
Reduced cortisol levels.
Pancreatic insufficiency.

CRISES
 Vaso-occlusive
 Haemolytic or hyperhaemolytic
 Aplastic
 Acute sequestration.
 Megaloblastic crisis-occurs only in folate
deficient pregnant patients
 Crises often precipitated by infections,
particularly malaria
VASO-OCCLUSIVE CRISIS
 This crisis is due to obstruction of blood
flow in the smaller venules , capillaries and
even in medium-sized or large arteries, as a
result of the increased viscosity and
sludging associated with sickling. Hence,
the term vaso-occlusion. Occlusion is
worsened by the increased adhesiveness of
sickled reticulocytes. Vaso-occlusion is the
pathophysiologic basis of most of the
clinical manifestations of the disease.
 ASSC may be defined by a decrease of at least 2
g/dL from the steady-state hemoglobin
concentration, evidence of increased
erythropoiesis such as a markedly elevated
reticulocyte count, and an acutely enlarging
spleen. ASSC has been reported as early as 5
weeks of age and in adults, but in most cases first
attacks occur between 3 months and 5 years of
age. They are often associated with viral or
bacterial infections; acute chest syndrome
occurred in 20% in one series . The usual clinical
manifestations are sudden weakness, pallor,
tachycardia, tachypnea, and abdominal fullness.
ASSC has been reported in 30% of children with
sickle cell anemia in Jamaica and 7.5% of
children seen at Duke University . The mortality
rate for first attacks was 12% in Jamaica .
sequestration crisis
 The spectrum of severity in this syndrome is
wide, ranging from mild splenomegaly to
massive enlargement, circulatory collapse
and even death. The diagnosis is usually
clinical, based on the enlargement of the
spleen with a drop in Hb level by more than
2g/dl. Imaging studies are rarely reqd to
confirm the diagnosis.
Sequestration crisis
 Commoner in younger children who have

HbSS anaemia and older children and
adolescents who have HbSC disease, but it
may occur even in adults.
 Children who have had one episode are far
more likely to have a recurrent event, and
the morbidity from this complication is
significant.
Reverse sequestration
 This is due to a reversal of the crisis. It is seen
during the recovery phase and is characterised by
a rapid rise of haemoglobin concentration
unrelated to blood transfusion, followed by
hypertension, congestive cardiac failure and
catastrophic intracerebral haemorrhage. Careful
monitoring of a sickle cell patient's blood pressure,
blood counts, haematocrits, haemoglobin S level
and plasma viscosity, even after the end of a
sequestration crisis, is recommended

Psycho-social complications
Sources of anxiety in SCD
include……
1.Persistent jaundice.
2.Frequent ill health.
3.Delayed puberty.
4.Poor growth.

Psycho-social complications..
 5.Non-acceptance by society.
….employment, marriage,e.t.c.
 6.Uncertainty about the future.
 7.Economic burden of the disease.
 8. significant number of school days
lost to crisis / hospitalization
 9. Intellectual attainment
Infections in SCD
 Microvascular
thrombosis/infarction in the lungs.
 Impaired local ventilation/
resultant hypoxia
 Metabolic abnormalities in
leucocytes.

Infections
 Progressive splenic infarction/fibrosis.
 Functional asplenia. By the age of 5 years,
95% of children with SCA in the U.S.will
have functional asplenia.
 This is not the case in Africa, because of
persistent splenic stimulation by malaria.
 High serum iron levels..chronic haemolysis,
frequent blood transfusion, compensatory
increase in iron absorption from the gut.
 Defective alternate pathway of complement
activation.

Any solution(s) to this threat?
 Accurate survival data for children with
SCD facilitate treatment and counselling of
patients and their families, guide public
health interventions , and provide the
foundation for future research.
 The best method to measure overall survival
is a cohort study; optimal cohorts should
include only subjects identified at birth or in
the first few months of life.
health-altering interventions
 1. Newborn screening
 2. Penicillin prophylaxis
 3. anti-pneumococcal vaccination
 4. better pain management
 5.family-patient education/ financial
support
 6 . Hydroxyurea
 7 chronic RBC transfusion
 8haemopoietic stem cell transplantation

Prognostic factors………
 1Genetic…persistent increase in HbF
…presence of HbC/ a-thal
Haplotype:
 The independent origin of the sickle mutation
opens the possibility that haplotypes could differ
in associated sickle cell disease severity. In african
populations, each is associated with different
degrees of severity.
 Senegal---on average, has the least severe clinical
course
 Benin---intermediate severity
 Bantu/CAR ---most severe disease
Co-existent a-thalassaemia trait
 In tropical africa, the frequency of a-thal

trait is about 25%. The lower MCHC causes
a reduction in the intracellular concentration
of HbS in a patient with sickle cell anaemia.
Therefore, there is less sickling and
haemolysis and the Hb level is higher,
leading to an amelioration of the disease.

genetic factors which may affect the
severity of sickling in an individual include:
 1. A higher than usual HbF level
 2. Coexisting alpha thalassaemia
 3.Double heterozygosity (e.g. HbSC)

Prognostic factors…
2. Environmental
 Social class
 Early diagnosis
 Good nutrition, availability of
health facilities, equable climate,
protection from malaria.

Prognostic factors….
 3.Unknown. Children from same

family ,living in same environment,
may present with differing degrees of
severity.

Prevention………………
 Genetic counselling….EDUCATION.
 Prenatal diagnosis/selective abortion.10w
 Routine neonatal screening reduces
morbidity and mortality.
 Neonatal blood spot test up to 10 days after
birth, to screen for major Hb disorders.
 Modern techniques ( High performance
liquid chromatography, isoelectric focusing)
allow the diagnosis to be made on neonatal
blood samples.
 There is a newly-developed, very
experimental, method for very early
testing for sickle cell disease and it is
highly controversial – carrying out in
vitro fertilization and then testing the
embryos for sickle genes before
implanting in the mother's womb.

 In vitro fertilization (IVF) combined with a
procedure called Preimplantation Genetic
Diagnosis (PGD) can improve a woman's
chances of having a healthy baby when
there is a family history of inherited genetic
diseases or conditions, or if a patient has
experienced miscarriages caused by embryo
chromosomal abnormality.
 Embryo biopsy with PGD is a procedure utilized
in conjunction with IVF to screen for genetic
and/or chromosomal problems before an embryo
is selected for uterine implantation. This is also
called "pre-pregnancy diagnosis". A number of
genetic disorders and/or chromosomal
abnormalities can be identified through PGD
including Muscular Dystrophy, Hemophilia,
Sickle Cell Anemia, Cystic Fibrosis, Tay Sachs,
Fragile X Syndrome, Turner Syndrome,
Huntington disease and Down syndrome.

 PGD allows us to differentiate abnormal
embryos from the normal embryos, so that
only normal embryos are transferred to the
uterus, In select patients, IVF with PGD
can significantly decrease miscarriage rates
and help women at risk for miscarriage
achieve a successful pregnancy.

Baby's genome lurks in
mother's blood: Study
 Building on the discovery that fragments of
foetal DNA are present in a mother's
plasma, the company and other scientists
are working to develop prenatal DNA tests
as an alternative to amniocentesis and other
invasive ways of collecting DNA from a
developing foetus that raise the risk of
miscarriage.
Summary
 SCD is an increasing health burden for
many countries, especially those in sub-
Saharan Africa
 With adequate intervention, there is an
opportunity to alter the course of the disease
for millions of people, especially young
children.
 International heath org such as the WHO
need
Friday, to2015be more active in advocating for 89
August 21,
..summary
 SCD programmes and services in
developing countries, especially those in
Africa.
 Interventions that have altered the health
and lives of people with SCD in developed
countries will work and save even more
lives in developing countries. These
interventions are affordable, if we get our
priorities right.
 THANK YOU FOR YOUR ATTENTION

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THE THREAT OF SICKLE CELL

DISEASE TO CHILD SURVIVAL

 Lecture delivered at the CPD of the MDCAN

 D.M . Olanrewaju, FWACP, FRCP Edin

 Professor of Paediatrics, Olabisi Onabanjo

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Global 5,476,407 312,302 100

Americas 386,430 12,802 4.6

Arab-India 1,147,477 46,826 16.9

Eurasia 256,163 7,493 3.0

Southeast Asia 2,535 21 0.0

Sub-Saharan Africa 3,580,207 235,681 75.5

Sickle Region 2010 2050 2010-2050

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Country 2010 2050 2010-2050

Global 305773 100 404190 100 +32.2

1. Nigeria 91,011 29.8 140,837 34.8 +54.7

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It depends on where the baby was

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 Tanzania....1.9 per 100 PYO

 USA......3 per 100 PYO (before pencillin p)

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 Just how this protection works is not

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 Protective effect of HbF delays onset

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 Pathologic changes occur in all organs

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 Progressive azotaemia/renal failure.

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Reduced growth hormone from

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 Commoner in younger children who have

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