HAEMOGLOBINOPATHI

ES

DR(MRS) MILDRED OLUCHI IZUKA (MBBCh, FWACP, FMCPaed)

CONSULTANT PAEDIATRICIAN / Dep.HOD
DEPARTMENT OF PAEDIATRICS
FEDERAL MEDICAL CENTRE UMUAHIA / COLLEGE OF HEALTH SCIENCES GREGORY
UNIVERSITY UTURU
 INTRODUCTION
Haemoglobinopathies are anaemias due to defective
haemoglobin (Hb) synthesis.
Defect in haemoglobin production(Quantity) and
function(Quality)
They are genetic abnormalities of the haemoglobin
molecule shown by changes in chemical
characteristics, electrophoretic mobility or other
physical properties.
 NORMAL HAEMOGLOBIN PATTERN
ADULT

HbA1 >95%
α&
ᵝ
HbA2 < 3.5%
α&
ᵟ
HbF < 2.5%
α&
ᵞ

HbF HbA2 HbA1

At Birth >80% 10% <10%

6 mon 10% 5% >85%

The type of chain an individual has whether α or is
ᵟ
genetically controlled.
Haemoglobins are designated to letters according to
when they were discovered.
HbA was 1st to be discovered then
HbA2—it should have been B
HbS ----it should have been C
And subsequently HbC, D, E,G,H
By laboratory tradition the electrophoretic Hb of
greatest concentration is named 1st.
HbAS means that HbA is > S
HbSC which means S is > C
 TYPES
There are two major types of haemoglobinopathies

• Sickle cell disease

• Thalassemia

The primary pathology in thalasseamia stems from the

quantity of globin production, whereas the primary
pathology in SCD is related to the quality of globin
produced.
SICKLE CELL DISEASE
 LEARNING OBJECTIVES
At the end of this lecture you should be able to:

 Provide an overview of Sickle Cell Disease from an in-depth

knowledge
 OUTLINE
• Introduction • Challenges
• Historical perspectives • Treatment
• Definition • Counselling
• Inheritance • Roles in SCD support
• Causes • Key messages
• Pathogenesis • Conclusion
• Signs and Symptoms • References
• Triggers of SCD
• Complications
• Diagnosis
 INTRODUCTION
Sickle Cell Disease (SCD), an inherited condition in which red blood
cells are not shaped as they should be is among the top ten non-
communicable diseases causing significant disability, morbidity and
mortality.

Nigeria ranks first as the sickle cell endemic country in Africa.

Sickle Cell Disease impacted negatively on the Nigeria's attainment of

goals 1, 2, 4, 5, and 6 of the Millennium Development Goals (MDGs)
 INTRODUCTION
Contributes the equivalent of 3.4% mortality in children aged under
five worldwide and, in Africa, 6.4%.

Worldwide distribution

No gender difference

Cuts across all social classes

 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.
Commonest genetic disorder affecting
Nigerian children
1:50 Births = SS
1:4 Births = AS
The prevalence of SCA in Nigeria
ranges from 0.4-3%.
Nigeria is said to have the highest
number of persons with the disease
and trait
 HISTORY OF SICKLE CELL DISEASE
Sickle Cell Disease has been in Africa for over 5000
years. For lack of scientific knowledge children with
SCD used to die very young.
The disease was known by different names in
different African Tribes: in Igbo land children suffering
from Sickle Cell Disease were regarded as demon
possessed or “Ogbanje”.
 HISTORY OF SICKLE CELL DISEASE
• A sample of other names include “Abiku” in the Yoruba
tribe in Nigeria, ahututuo (from the Twi tribe in Ghana);
chwecheechwe (from the Ga tribe of Ghana ) and
nuidudui (from the Ewe tribe of Togo). Many tribal
names were imitations of the cries and moans of the
sufferers, forming such phrases as "body chewing" or
"body biting" which described their terrible torments
 HISTORY OF SICKLE CELL DISEASE

In 1904, a resident Doctor named Ernest Edward while examining the blood
of a 20 year old dental student from a wealthy black family in Grenada by the
name Walter Clement Noel, described his blood cells as “peculiar, elongated
and Sickle shaped”.

By (1910) James B. Herrick another Doctor became the first person to coin
the term “Sickle Shaped” to describe this peculiar appearance of the red
blood cell of the dental patient (Noel).
The story goes this way:
Walter Clement Noel went to Dr. James B. Herrick with
complaint of pain episodes and symptoms of anaemia. Dr.
Herrick assigned Noel’s case to a resident Doctor by name
Dr. Ernest Edwards who examined Noel’s blood under the
microscope and saw red blood cells he described as
“having the shape of a sickle”. Herrick knowing that there
was need for further investigation of this abnormal finding,
published a paper in one of the medical journals in which
he used the term “sickle shaped cells”.
In 1922, after three more cases were reported, the disease
was named “Sickle cell anaemia” by Verne Mason. The
disease got its name from the crescent shape of the red
blood cells which resembles a farm tool called a “sickle.”
One long-held theory as to why it was so common in the
tropics was its association with malaria. It was hypothesized
that sickle cell trait offered protection against malaria. Those
with the trait did not succumb to malaria as often as those
without it and that when they did, their disease was less
severe and because of this survival advantage of carriers who
are more likely to survive to reproduce, the sickle cell gene
proliferated in malaria endemic areas. E.A. BEET (1940s)
 WHAT IS SICKLE CELL DISEASE?
Sickle cell disease is a generic term that refers to a condition in which
an individual/ person has inherited two abnormal haemoglobin genes
at least, one of which is the sickle haemoglobin gene.

• Inherited
• Haemoglobin genes
• Abnormal Haemoglobin
• Two abnormal Haemoglobin genes
Some Forms of Sickle Cell Disease
• Haemoglobin SS (commonest)
• Haemoglobin SC
• Haemoglobin Sβ0 thalassemia
• Haemoglobin Sβ+ thalassemia
• Haemoglobin SD
• Haemoglobin SE
• Haemoglobin CC
• Hereditary persistence of HbF

 Genotype AS (HbAS) had inherited one abnormal haemoglobin gene

and are called Carrier state or sickle cell trait
How Is Sickle Cell Disease Inherited?
Autosomal Recessive

AS + AA:
• 50% chance of AS,
• 50% chance of AA

AS + AS:
• 25% chance of SS
• 25% chance of AA
• 50% chance of AS

SS + AS
• 50% chance of AS,
• 50% chance of SS
 It is important to keep in mind that each time this couple has a child;
the chances of that child having sickle cell disease remain the same.

In other words, if the first-born child has sickle cell disease, there is
still a 25 percent chance that the second child will also have the
disease. Both boys and girls can inherit sickle cell trait, sickle cell
disease, or normal haemoglobin.
 WHAT CAUSES SICKLE CELL
DISEASE?
A point mutation at position 6 in the β-globin chain
of haemoglobin.
This change leads to insertion of valine (a fat soluble
amino acid) at this 6th position instead of glutamic acid
(a water soluble amino acid) for HbS.
For HbC lysine (a fat soluble amino acid) replaces
glutamic acid (a water soluble amino acid) at this 6 th
position
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:
• 1.Benin (BEN)-found in Nigeria
• 2.Senegal (SEN)
• 3.Bantu (BAN)
• 4.Cameroon (CAM ) and
• 5.Saudi Arabia/India (SAI)
NORMAL RED BLOOD CELL VERSUS
SICKLE RED BLOOD CELL
 PATHOGENESIS
The haemoglobin 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 haemoglobin
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.
FIGURE 1

29
 PATHOGENESIS
The picture is different with sickle haemoglobin.
Sickle haemoglobin exists as isolated units in the red
cells when they have oxygen bound. When sickle
haemoglobin 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
 PATHOGENESIS
Diameter of RBC =7microns
Diameter of capillaries =3microns
Polymers tend to grow from a single start site (called a nucleation
site) and often grow in multiple directions. Star-shaped clusters of
hemoglobin S polymers develop commonly.
 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

32
 PATHOGENESIS
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 itself.
 PATHOGENESIS
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
 FACTORS ENHANCING SICKLING
Hypoxia
Presence of WBC.
 ” of Bacteria
Fever
Dehydration
Metabolic acidosis
 PATHOGENESIS
Sickle RBCs adhere to 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
haemolytic 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.

Saturday, March 30, 2024 38

PATHOGENESIS
 SICKLING AND O2 DELIVERY
SCD differs from other anaemias in that:
 The cardiac output is higher than in anaemias of
comparable severity;
 O2 pressure and saturation of arterial blood are lower;
 O2 pressure and saturation of venous blood are
higher.
 SCD AND O2 DELIVERY

Thus, there is a reduction in A-V saturation and

significant impairment of O2 unloading to the tissues
in SCD.

These presumably result from the intracellular

gelation and vascular obstruction that are unique to
SCD
 SIGNS AND SYMPTOMS
The symptomatology of SCA is protean and any organ
or system in the body can be affected
No symptom in early infancy because of the
protective effect of HbF.
“sickle cell crises”.
• vaso-occlusive crisis (Painful crisis)
• acute anaemic crisis. (sequestration crisis and
aplastic crisis)
Steady state
 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.
DACTILYTIS
JAUNDICE
 PRESENTATION AFTER 2 YEARS
Failure to thrive
Anaemia, jaundice
Infections
Crises
Sickle cell habitus….long, thin limbs, protuberant
abdomen, 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.
 OSTEOMYELITIS
 Tend to be diaphyseal
Symmetrical
Multifocal
Causative organism are the same with the other
population (Staph Aureus)
There is increased incidence of salmonella infection
in them than in the other population
AVASCULAR NECROSIS OF FEMORAL
HEAD
 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.
 ACUTE CHEST SYNDROME
The aetiology is multifactorial and includes stasis,
hypoventilation, infection, fat embolization from
bone marrow necrosis and microthrombi in the
pulmonary 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.
55
 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.
 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
paediatric sickle cell disease.
RISK FACTORS FOR INTRACRANIAL
HAEMORRHAGE
Low steady state Hb
High leucocyte count
Aneurysms which have bled in pts with SCD have
successfully been treated with interventional neuro-
radiology (embolization with coils) or surgery
(craniotomy and clipping). Adults with SCD are at risk
of recurrent intracranial haemorrhage.
 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.
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
Progressive azotaemia/renal failure.
Priapism.-
Nephrotic syndrome.
Renal medullary carcinoma
 PRIAPISM
Findings suggest an association of priapism with
increased hemolysis. Hemolysis decreases the
availability of circulating nitric oxide, which plays an
important role in erectile function
Recent work suggests that haemolytic anaemia is the driving force
behind some complications of SCD because of its effects on nitric
oxide (NO) bioavailability. NO, by binding soluble guanylate cyclase,
converts cyclic guanosine triphosphate (cGTP) to cyclic guanosine
monophosphate (cGMP), relaxing vascular smooth muscle and
causing vasodilation. Plasma haemoglobin liberated from
intravascularly destroyed sickle erythrocytes consumes NO-producing
methemoglobin while catalyzing the production of oxidant radicals
and adhesion molecules such as vascular cell adhesion molecule . The
normal balance of vasoconstriction/vasodilation is therefore skewed
toward vasoconstriction.
 PRIAPISM
Phosphodiesterase-5A dysregulation in penile
erectile tissue is a mechanism of priapism.
In SCD, NO deficiency secondary to hemolysis may
downregulate PDE5A and its downstream effectors so
that non–NO-mediated uninhibited increases in cGMP
result in uncontrolled erection. Sildenafil and similar
PDE5A inhibitors may paradoxically alleviate or
prevent priapism in these states.
 PSYCHO-SOCIAL COMPLICATIONS
Sources of anxiety in SCD include……
Persistent jaundice.
Frequent ill health.
Delayed puberty.
Poor growth.
PSYCHO-SOCIAL COMPLICATIONS..

Non-acceptance by society.
 Employment, Marriage, e.t.c.
Uncertainty about the future.
Economic burden of the disease.

70
 INFECTIONS IN SCD
Microvascular thrombosis/infarction in
the lungs.
Impaired local ventilation/ resultant
hypoxia
Metabolic abnormalities in leucocytes.

Saturday, March 30, 2024 71

 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.
Saturday, March 30, 2024 72
 CRISES
Vaso-occlusive
Haemolytic
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.
 HAEMOLYTIC CRISIS
This occurs when RBCs are broken down at a more rapid rate than
that which obtains during the steady state of the disease.
Usually precipitated by malaria and bacterial infections. Features
include:
Severe anaemia, Cardiac failure
Jaundice, hepatomegaly.
Encephalopathy-seizures, altered sensorium
The terms ‘haemolytic’ and ‘hyperhaemolytic’ are often used
interchangeably, but the latter technically refers to co-existence of
SCA and G6PD.
 APLASTIC CRISIS
There is a shut down of the bone marrow which is
usually limited to the red blood cell precursors.
The patient becomes profoundly anaemic and may
go into high-output cardiac failure.
Anaemia recurs after blood transfusions, until the
crisis is over.
Several viruses are associated with this syndrome.
The most common agent is parvovirus B19.
 APLASTIC CRISIS
• Parvovirus B19 has a specific receptor, the P antigen on the
erythroid precursors. Therefore, only erythrogenesis is
affected in aplastic crisis.
• Associated symptoms may include fever, headache, myalgia,
arthralgia, resp and git symptoms.
• Diagnosis is confirmed by the presence of IgM to Parvovirus
B19 or the presence of parvovirus DNA. Immunity conferred
following infection is life-long.
• The condition is self – limiting in most instances, but
supportive therapy including transfusion may be necessary.
Steroids are also beneficial
 ACUTE SEQUESTRATION
Pooling of blood in the spleen is a frequent occurrence in children with
sickle cell anaemia, particularly in the first few years of life, resulting in
splenic sequestration crisis. It may also affect the liver.
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.
 TRIGGERS OF SICKLE CELL CRISIS

Extremes of temperature/ sudden change in temperature, which can

make the blood vessels narrow.

Very strenuous or excessive exercise or physical exertion, due to

shortage of oxygen.

Dehydration, due to low blood volume.

 TRIGGERS OF SICKLE CELL CRISIS

Infections including malaria.

Injury (including surgery).

Stress (both Physical and emotional stress).

High altitudes, due to low oxygen concentrations in the air.

 TRIGGERS OF SICKLE CELL CRISIS

Use of alcohol or caffeine.

Smoking.

Pregnancy.

Other medical conditions, such as diabetes.

HOW IS SICKLE CELL DISEASE
DIAGNOSED
Prenatal

Neonatal screening

Post neonatal testing

 DIAGNOSIS
Clinical …….80% of cases.
Laboratory diagnosis:
Electrophoresis…cellulose acetate
 ….citrate agar.
HbD (punjab) has the same electrophoretic
mobility as HbS,

83
 DIAGNOSTIC METHODS
Full blood count, blood film and reticulocyte count, bilirubin
 Sickle solubility test (e.g. sickledex)
 Hb electrophoresis using cellulose acetate or agar gel
 High performance liquid chromatography (HPLC)
 Isoelectric focussing (IEL)
 Polymerase chain reaction (PCR)
 Supplementary genetic tests

84
 LAB FINDINGS

Increased retic count of 5-15%

WBC 12-20,000
Normal MCV
Hb 5-9g/dl
Normal or slightly increased platelet count.
Normal differential or preponderance of
neutrophils.
Saturday, March 30, 2024 85
 LAB FINDINGS
Nucleated RBCs indicate severe anaemia
Target cells, poikilocytosis, anisocytosis, hypochromic
cells, sickled RBC
Howell-Jolly bodies.
Markedly hyperplastic bone marrow with erythroid
predominance.

86
 DIFFERENTIAL DIAGNOSIS
Leukaemia.
Rheumatic fever.
Juvenile rheumatoid arthritis.
Osteomyelitis.
Etc, etc.

Saturday, March 30, 2024 87

 MANAGEMENT
Health Maintenance to Prevent Complications..
Steady state

Managing crisis or complications of SCD

 MANAGEMENT
Health Maintenance to Prevent Complications..
Steady state

 Examining the person (Height, Weight, Blood

Pressure)
 Determine and record physical/haematological
Parameters
 Avoid factors that encourage sickling.
 Giving medicines and immunizations
Folic acid supplementation.
Malaria prophylaxis.
Immunisation……pneumococcal
 ……Hib
 ……Hepatitis B
Hydroxyurea therapy
 MANAGEMENT
Screening tests/evaluation (Baseline/warning signs)
 Eye/Ear examination

 Education and guidance

 Supportive counselling

Cognitive Screening(Individualized Education Program)

 MANAGEMENT
Transcranial Doppler (TCD) Ultrasound Screening

Erythracytopharesis

Chronic transfusion

POTENTIAL CURE
• Bone marrow transplant
• HSCT
• Gene therapy
 MANAGEMENT OF VOC
The history and physical exam should always
incorporate the evaluation of pain.
If possible, use validated pain scales
Determine if the patient has been able to sleep
Monitor the patient’s reactions during the
examination, such as grimacing, stiffness, ease of
movement.

Saturday, March 30, 2024 93

 MILD TO MODERATE VOC

 Bed rest at home.

 Liberal oral fluids.
 Analgesics-paracetamol, codeine, NSAIDs
 Identify and treat cause.
 Oxygen administration (even hyperbaric oxygen) is
unhelpful in VOC.

Saturday, March 30, 2024 94

 SEVERE VOC
• Admit
• Administer analgesics commensurate with degree of
pain.
• I.V. fluids 2000-2500ml/m2/24hrs,in form of ½ st
Darrows in 5% dextrose or 5% Dextrose in 0.45%
Saline.
• Identify and treat cause.
• It is wise to give antimalarials and antibiotics until
results of appropriate samples are available.
Saturday, March 30, 2024 95
 MX OF VOC-CURRENT TRENDS
 PCA, NCA.
 Epidural infusions
 Psychologic intervention….cognitive and behavioral
therapy (CBT) can reduce distress.
 Identify and treat cause.

Saturday, March 30, 2024 96

 HAEMOLYTIC CRISIS…….MX

 ADMIT.
 Give O2
 Transfuse in presence of:
 Anaemic heart failure.
 PCV below 15%.
 Significant fall in pcv below steady state value.
 Overwhelming infection.
 Diuretics.
Saturday, March 30, 2024 97
 MX OF ACUTE SEQ. CRISIS
Treat shock.. elevate foot of bed, give parenteral
steroids(methylpred or hydroc.)
Packed cell transfusion, 5-10 ml/kg.
Some sequestered cells will return to the circulation. (reverse
sequestration) 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.
Partial E.B.T.
Splenectomy.
Saturday, March 30, 2024 98
INDICATIONS FOR SPLENECTOMY IN
SCD
Recurrent acute splenic sequestration crisis.
Hypersplenism
Splenic abscess
Massive splenic infarction

Saturday, March 30, 2024 99

 APLASTIC CRISIS…..……MX
Intermittent oxygen.
Whole blood transfusions
Steroid therapy.
?Bone marrow transplantation.
Successful use of Gamma Globulin and
Erythropoietin in a Sickle Cell Aplastic Crisis has been
reported.
Saturday, March 30, 2024 100
At the time of aplasia, the child with sickle cell
disease is highly contagious. If the diagnosis of
aplastic crisis is made, the child should be strictly
isolated from all vulnerable groups, such as pregnant
women, immunocompromised children and all
children with haemolytic anaemias

Saturday, March 30, 2024 101

 MX OF INFECTIONS
Common organisms…….H. influenza,
pneumococcus, salmonella spp., S. aureus.
Choice of antibiotics guided by the common
organisms antibiogram

Saturday, March 30, 2024 102

 ADVICE FOR PEOPLE LIVING WITH
SCD
Learn as much as they can about the disease.

Pursue a healthy lifestyle

Avoid situations that may set off a crisis

Take their medicines as their doctor prescribes.

Get any medical and lab tests or immunizations that their doctor orders.

Teachers need to know what to watch for and how to accommodate them

Make and keep regular appointments with their SCD doctor or medical team.
ROLES IN HELPING SOMEONE WITH SICKLE CELL DISEASE

Individual roles

Family roles

School roles

Government roles
 PREVENTION/ BREAKING THE CYCLE
Improved knowledge through education

Knowing their Genotype and making appropriate choices

Medical errors

Falsification of results

Conceal/ denial
GENOTYPE COMPATIBILITY GUIDE
Thank you all for listening
 SUGGESTED READINGS
Nelson textbook of Paediatrics, 19TH & 20TH edition.
Paediatrics and child health in a tropical region, 3rd edition
Paediatric Heamatology and Oncology (Oxford Specialist Handbooks
in Paediatrics)
 REFERENCES

1. Okpala I. “Sickle cell disease and Thalassemia” in Okpala I., Johnson C. (eds.)
Synopsis of Hematology including blood diseases in the tropics. 1st ed.

2. Adekile AD., Adeodu OO. “Haemoglobinopathies” In Azubuike JC., Nkanginieme

KEO.(eds.). Paediatrics and child health in a tropical region. 2nd ed. Owerri,
African Educational Services; 2007:373-390.

3. https://www.healthline.com/health/sickle-cell-crisis-management#prevention

4. https://www.healthline.com/health/sickle-cell-anemia#risk-factors
 REFERENCES
1. (https://sicklecellanemianews.com – Sickle cell’s prognosis taught me to live with purpose).

2. www.dictionary.com

3. www.medicalnewstoday.com

4. www.kidshealth.org

5. www.express.co.uk

6. www.gettyimages.com

7. www.shutterstock.com

8. www.sicklecellsociety.com
Q&A