MANAGEMENT OF SICKLE CELL ANAEMIA IN CHILDREN 2013 Prof Jiya.ppt

SCA

1. MANAGEMENT OF SICKLE CELL
ANAEMIA IN CHILDREN
BY
PROF NMA MUHAMMED JIYA, MBBS(ABU),MMCPaed, FWACP.
PROFESSOR/CONSULTANT PAEDIATRICIAN AND HOD
DEPARTMENT OF PAEDIATRICS,
UDUS/UDUTH, SOKOTO.
1

2. INTRODUCTION
•Sickled red blood cells were first observed in
1910 by Herrick in an acutely ill Black West
Indies Student.
•The mutation responsible for HbS gene
occurred at least thrice in different parts of
Africa.
•HbS results because of substitution of
glutamic acid by valine in position 6 of the B
chain.
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3. Introduction cont’d
•Prevalence rate of HbAS (sickle cell trait) in
Nigeria is about 25% to 40%(37.5 to 60million
Nigerians are carriers of this disease).
•Prevalence rate of sickle cell anaemia(SCA)
(HbSS)-homozygous condition is 3%
(4.5million) in Newborns and 1-2% (1.5 to
3million Nigerians are SICKLERS) in general
population in Nigeria.
•About 80,000 cases per state on average!
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4. 4

5. Sickle Cell Global Picture.
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6. PATHOGENESIS
•The pathogenesis of SCA results from
deoxygenation of HbS with formation of
spindle-shaped liquid crystalline bodies called
tactoids.
•Red blood cells (RBC) containing HbS then
become deformed and rigid (Sickled).
•There is also increased mechanical fragility
and increased destruction of RBCs
predominantly in the extravascular sites.
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7. Normal And Sickled RBC.
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8. •Initially the sickled RBC can revert to normal
shape when arterial oxygen tension increases.
•It may undergo series of sickle-unsickle cycles
before it becomes irreversibly sickled (ISC)
•Factors precipitating sickling include:
1-Decreased oxygen tension.
2-Presence of bacteria infection
3-Fever mostly from malaria infection

Pathogenesis cont’d
8

9. Pathogenesis cont’d
4-Increase white blood cells from infections.
5-Dehydration.
6-Metabolic acidosis.
•Free radicals also play role in the
pathophysiology especially superoxide.
•Free radicals are unstable because they have
single electrons.
9

10. Pathogenesis cont'd
•They are therefore highly destructive: said to be the
single most destructive agent in nature.
•The most important damage from point of view of SCA
is LIPID PEROXIDATION.
•This results in altered membrane structure and
function of RBCs.
•Process of lipid peroxidation could be terminated by
protection mechanisms using anti-oxidants like,
1-Vitamin E.
2-Vitamin C (Ascorbic acid).
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11. Pathogenesis cont’d
3-Carotene.
4-Riboflavin.
•It should be noted that spontaneous oxygen
radical generation occurs in SCA.
•Iron (Fe) acts as a catalyst in the production of
the destructive hydroxyl radical.
11

12. CLINICAL FEATURES
•Most infants (6months-
1year) may present
with dactylitis, swelling
of dorsa of hands/feet
which is tender, warm,
pitting (Hand-foot
syndrome). This is
usually due to
ischaemic necrosis of
the small bones.
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13. 13

14. CLINICAL FEATURES Cont’d
•Other features include Failure to thrive,
Recurrent Anaemia/Jaundice, Infections,
Crises and sickle cell habitus (frontal or
parietal bossing of the skull, gnathopathy,
protuberant abdomen and thin and long
extremities).
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15. SICKLE CELL CRISES
(1)-Vaso-occlusive (pain) crisis.
(2)-Hyper haemolytic (Anaemia) crisis.
(3)-Acute sequestration crisis.
(4)-Hypoplastic or Aplastic crisis.
•The crises can occur alone or in combination.
•Vaso-occlusive crisis is the most frequent and
severe.
•Can result in complications in virtualy all organ
systems in the body.
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16. Sickle cell crises cont’d
i. Musculo - skeletal system:
•High incidence of
osteomyelitis.
•Pathological fractures.
•Avascular necrosis of
femoral head (ANFH).
•Chronic leg ulcers.
16

17. Sickle cell crises cont’d
ii. There is sickle cell Hepatopathy.
iii. Also sickle cell Nephropathy.
iv. Neurological complications: Convulsion,
Aphasia and spastic hemiplegia resulting from
CVA(Cerebrovascular accident).
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18. Sickle cell crisis cont’d
•Overall incident of CVA in SCA patients is
about 4%.
•CVA occurs more frequently in age group
below 10years, particularly those between 2
and 5years of age.
•Infarctive strokes occur in 65 to 80% of cases
and haemorrhagic strokes in 20 to 35% of
patients.

18

19. Sickle cell crisis cont’d
•Cerebral infarction is observed predominantly
in children less than 15years and at a mean
age of 7years.
•Haemorrhagic strokes occur mostly in adults
with a mean age of 25years.
V. Psycho-social complications which are
sources of anxiety include the following,
persistent jaundice,
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20. Sickle cell crisis cont’d
Frequent ill health (‘’sickler’’).
Delayed secondary sexual
characteristics.
Poor growth.
Non-acceptance by society.
Loss of job, discriminated against in
various ways.

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21. Wed.29/Sept./2010 @NMJ 2010 21

22. DIAGNOSIS
•Clinical Diagnosis.
•Laboratory Diagnosis using Electrophoresis
which may be:
–cellulose acetate
–citrate agar.
Patterns may be HbSS, HbSS + F(common ones).
. High Performance Liquid Chromotography
(HPLC) which is now available in UDUTH &
FMC Kb. It can determine percentage Foetal
Haemoglobin and other variants of haemoglobin
22

23. MANAGEMENT DURING CRISES
1.Vaso-occlusive Crisis
•Painful crisis is the most common manifestation
of sickle cell anaemia (SCA),
•It accounts for significant number of hospital
admissions in most hospitals.
•Mild forms can often be treated satisfactorily
while the child stays at home by these measures:
Bed rest, Provision of warmth for the patient,
Liberal oral fluid intake, Analgesics such as
Ibuprofen or Paracetamol.
23

24. Management during crises cont’d
*Severe forms can best be treated in hospitals
by measures such as
a)Intravenous fluid usually about 2000 –
2500ml/m2/24hrs using 4.3/0.18%
Dextrose/saline made up to D10 or 0.45%
Normal saline.
b)Analgesics like narcotics should be sparingly
used, for example Pethidine or Morphine.
24

25. Management during crises cont’d
•However, parenteral Pentazocine,Piroxicam,
Diclofenac sodium and Ibuprofen are good
alternatives that should be used for not more
than 24hrs and thereafter change to oral
forms
•Psychological intervention, that is, Cognitive
Behaviour Therapy (CBT) has been shown to
significantly reduce psychological distress
from pain as well as hospital admissions. It
improves coping ability in patients.
25

26. Management during crises cont’d
•Patient Controlled Analgesia(PCA) ,Nurse –
Controlled Analgesia(NCA), and Epidural
infusions are new techniques of pain
management of patients with SCA with VOC
especially in specialized centres. They will be
attended to by Nurses whose special interest
and training is the management of children’s
pains and they will be provided with the
techniques of analgesia by competent, trained
anaesthetic staff.
26

27. Management during crises cont’d
2. Haemolytic crisis
•It is best managed in the hospital because it may
be difficult to predict the rate at which the
packed cell volume will fall.
•In severe anaemia (PCV < 15%),the patient
should be placed on Oxygen as an emergency
measure while awaiting blood transfusion
•In majority of cases, the cause of the anaemic
crisis is due to MALARIA especially in TROPICS.

27

28. Management during crisis cont’d
•Therefore, the patients should be screened for
Malaria and Bacterial infection. Those found to
be positive should be treated accordingly.
•Usually, the patients are given Packed cell blood
that are screened for HIV ,Hepatitis B and C
viruses under the cover of IV Frusemide.
3. Acute Sequestration crisis
This is treated in similar way using packed cell
transfusion. In addition, urgent attention should
be paid to the treatment of shock in this
condition.
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29. Management during crises cont’d
•Parental steroid therapy (Hydrocortisone or
Methylprednisolone) is usually administered as
adjuncts in the control of shock in patients with
acute sequestration crisis.
4. Aplastic crisis
This is a self –limiting but life-threatening
complication of SCA which is often triggered by
the PARVOVIRUS. It may sometimes be
precipitated by bone infarction or folate
deficiency.
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30. Management during crises cont’d
Aplastic crisis is managed by giving
Intermittent Oxygen administration, Whole
blood transfusion and Steroid therapy.
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31. MANAGEMENT OF COMPLICATIONS
1. Infections
•Salmonella species and Staphylococcus
aureus have been observed to be common
infecting agents in patients with SCA in
Developing countries, in addition to
Pneumococcus.
•Treatment of infections in SCA should be a
combination of chloramphenicol and
flucloxacillin or Ciprofloxacin and
Metronidazole pending sensitivity results.31

32. Management of complications cont’d
2. Leg ulcers
•Zinc sulphate cream or daily Eusol dressings.
•Chronic transfusion programme.
•Epanutin therapy has been beneficial in some
patients.
•Application of honey topically is beneficial.
3. Priapism
•Intracavernous injection of adrenergic
agonists(ICT) is one of the best treatments as of
now and Exchange blood transfusion.
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33. Management of complications cont’d
4. Ocular complications
•Neovascularisation of the optic disc is now
being successfully treated with LASER
COAGULATION especially in those with HbSC
5. Cerebrovascular accident(CVA) or Stroke
•Exchange blood transfusion or partial
exchange transfusion in acute states.
•Then chronic transfusion programme to
reduce recurrence.
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34. Management of complications cont’d
6. Avascular necrosis of the head of femur
•Majority of SCA have responded very well to
PLUG OSTEOSTOMY or total hip replacement.
•Progression could be slow down considerably
with the use of oral Hydroxyurea
(Hydroxycarbamide). We recently
encountered a 14year girl with Triple ANFH
and a 12year old boy with Bilateral ANFH
whose progression of the disease has slow
down remarkably with use of oral Hydroxyurea34

35. RECENT ADVANCES IN SPECIFIC THERAPY
•The fundamental cause of SCA is the
DECREASED DEFORMABILITY of sickled red cell
produced by gelation of haemoglobin S.
Therefore ,partial inhibition of gelation should
reduce clinical severity while complete
inhibition should result in a ‘’CURE’’.
•The following agents have been tried with
varying success rates.
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36. Recent Advances in therapy cont’d
1. Induction of foetal haemoglobin (HbF)
•Hydroxyurea, Recombinant human
erythropoietin and RESVERATROL , which is a
natural dietary polyphenol have all been
found to enhance the synthesis of HbF but has
a lot of side effects. More will be said about
Hydroxyurea later.
2. Sodium cromoglycate
•Inhalational or oral forms have been found to
reduce sickle cells in SCA.
36

37. Recent Advances in therapy
cont’d
3. Fagara zanthoxyloides (Zanthoxylum
zanthoxyloides) which is an aqueous extract of
the root of a chewing stick (called ‘’Orin ata”
in Yoruba language) local to Nigeria.
•They inhibit sickling of RBCs in SCA and are
also able to reverse already sickled ones.
• Clinical trials have confirmed their efficacy.
37

38. Recent Advances in therapy
cont’d
4. NICOSAN
•It is said to be related to Fagara zanthoxyloides.
•It was developed from NIPRISAN by Scientists at
the National Institute for Pharmaceutical
Research and Development, Idu, Abuja, Nigeria,
in 2002 and was launched in 2006.
•Nicosan is non-toxic natural herbal drug
composed of extracts from local plants that are
indigenous to Nigeria.
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39. •250mg of Nicosan contains:
1.Sorghum bicolor leaves extract------ 70.0mg
2.Pterocarpus osun stem extract-------35.0mg
3.Piper guineenses seed extract--------30.0mg
4.Eugenia caryophyllum plant-----------25.0mg
5.Potash---------------------------------------90.0mg
•Starch------------------------------------------ q.s
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40. NICOSAN
40

41. Recent Advances in therapy
cont’d
•NICOSAN IS NOT CURATIVE TREATMENT FOR
PATIENTS WITH SCA.
•It disturbs sickling and hence no crisis, therefore,
the blood remains like normal ones and
thereafter live like a normal healthy person.
•It reduces significantly the incidence of crisis in
SCA if taken consistently according to Dr Ramseh
Pandey of Xechem pharm Nig Ltd.
•It is prophylactic management of SCA.
•Side effects of Nicosan include
hyperactivity/energetic and insomnia. It is no
longer available and the Company has folded up!
41

42. Recent Advances in therapy
cont’d
5. Bone marrow transplantation
•It has curative potential for patients with SCA.
•Presently not readily available in Nigeria
although one was said to have done in UBTH,
Benin sometimes last year. Details not
available two year after the “transplant”!
•It costs about N21million outside Nigeria
hence not affordable by vast majority of SCA
patients in the country.

42

43. Recent Advances in therapy
cont’d
Indications for the Bone marrow
transplantation in SCA include:
a) CVA, Stroke or CNS haemorrhage
b) Recurrent acute chest syndrome
c) Sickle cell nephropathy
d) Recurrent debilitating pain
e) Bilateral proliferative nephropathy and visual
impairment
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44. Recent Advances in therapy
cont’d
6. Stem cell transplantation
(SCT)
•SCT has the potential of
curing SCD and halting end-
organ damage.
•SCT after reduced- intensity
conditioning (RIC) has been
suggested as a safer
approach for the treatment
of SCD
•It is also not available in
Nigeria.
44

45. Recent Advances in therapy
cont’d
7. Role of Anti- oxidants
•Many recent studies have confirm that
peroxidative damage occurs in sickle
erythrocytes in vivo and that this may play a
role in chronic haemolysis and vaso-occlussive
component of the disease.
•Some our studies in Sokoto and elsewhere
have shown beneficial effects of vitamin C and
E whose serum levels are significantly low in
patients with SCA.
45

46. Recent Advances in therapy
cont’d
•These anti-oxidants ,vitamins C and E act by
protecting the RBC membrane from oxidative
damage through detoxification of the oxygen
radicals generated by sickle haemoglobin.
•Their use are therefore advocated for patients
with SCA.
46

47. HYDROXYUREA(HYDROXYCARBAMIDE
)
Primary laboratory effects include:
1. HbF induction
2. Lowering of WBC and ANC
3. Decreased Platelet count
4. Decreased Adherence of sickled RBC
to capillary endothelium

48. Indications for the use of Hydroxyurea
1. Frequent painful events
2. Dactylitis
3. Acute Chest syndrome
4. Stroke prophylaxis
5. Elevated Transcranial Doppler
velocities
6. Parental request

49. There is compelling evidence that
Hydroxyurea can reduce painful events
and hospitalizations in children of all
ages with HbSS according to Strouse JJ
and Heeney MM(2012)

50. MANAGEMENT IN STEADY STATE
•This include regular clinic visits, folic acid and
paludrine,Oral Penicillin V, Conjugated
vaccines against encapsulated bacterial
pathogens, balance diet, avoidance of
exposure to severe weather conditions and
strenuous exercise as well as prompt
treatment of complications whenever they
occur.
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51. PROGNOSTIC FACTORS IN SCD
1. Genetic
•Persistently high HbF
•Low total HbS
•Hbs/B+
51

52. PROGNOSTIC FACTORS IN SCD cont’d
2. Environmental
•High social class
•Early diagnosis
•Understanding parents
•Good nutrition
•Availability and accessibility of Health services
•Equable climate
•Protection from malaria and other infections.
52

53. Support Groups for Sickle Cell Patients In Nig.
SICKLE CELL FOUNDATION, NIG.SICKLE CELL ASSOCIATION, NIG.
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54. PROGNOSTIC FACTORS IN SCD cont’d
3. Unknown
•Children from same family may present with
differing degrees of severity.
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55. KING TUT OF EGYPT DIED OF SICKLE CELL !
SO BE AWARE .
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56. THANK YOU FOR LISTENING.
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