CASE PRESENTATION

SICKLE CELL
Kevin Wandago
HSM201-0138/2018

SUPERVISOR: DR.GITAU
 Biodata
• G.N
• 3yrs Female
• Redidence- pipeline
• Informant- Mother
• Home county-Bungoma
• Day 2 of admission
 Chief complaints
• Cough- 4/7
• HOB- 4/7
• Yellowing of skin- 4/7
• Vomiting- 2/7
 HPI
• The patient was well until 4 days prior to admission when she
developed a cough. It was productive with yellow sputum, which
was copious in amount and foul smelling. The cough was present
throughout the day and had no diurnal variation, had no identifiable
triggers, and was relieved by over the counter Cough syrup. The
mother also reports noticing fast breathing. Patient also had a
running nose, however, there was no nasal congestion, wheezing or
snoring, and no history of reported foreign body ingestion. There
was no one at home with similar symptoms, no history of contact
with persons with chronic cough, or known TB patient. There was no
weight loss noticed.
• There was hotness of the body during this period, with no diurnal
variation, and no drenching night sweats. It was relieved by exposure
and transiently by the cough syrup. There were no shivers.
• On the same day, the mother reports noticing yellowing of the child’s
eyes and skin upto the level of the soles of the feet. There were no
pale stools or dark urine, no abdominal pain or distension. No hx of
contact with anyone with similar syptoms. No diarrhea or
constipation. However, the patient had a reduced appetite and could
not eat or drink and was weak and lethargic. There was vomiting for 1
day. It was non-projectile, non-billous and postprandial. Not blood
stained. The contents were food. There were 2 episodes, last episode
was on the day of admission.
• There is no recent history of travel to malaria endemic regions. No
family history of sickle cell disease, no previous hx of swelling of joints
of hands or feet, and no past history of jaundice, and no previous
history of blood transfusion. Both parents home county is Bungoma
Past medical history
• Index admission
• No hx of prevous surgeries
• No chronic illness hx or medication use
• No known food or drug allergies
Birth history
• Born at term (38/40) via SVD in hospital. Bwt of 3.6kgs. Cried
immediately after birth. No complications post-natally. No
admission to NBU & breastfeeding was initiated within 1 hour after
birth.

Antenatal history
• 6 ANC visits, first was at 10/40.
• IFAS & TT administered
• RVD & VDRL - NR
• Blood group – B+ve
• No complications/illnesses during pregnancy
• No substance use during pregnancy
Nutritional history
• EBF for 6/12, weaned on mash potatoes, matoke,
spinach, milk and porridge.
• Currently feeds well, on family food, however has a
poor appetite since onset of symptoms.
• Last 24 hrs- water only.

Immunization history
• Patient is fully immunized. No DVI booklet
• BCG scar present
Growth and Development- Milestones

• Gross motor- walk without support at 12 months, can now run (adequate)
• Fine motor- grasp objects at 8 months, can now draw (adequate)
• Language- one word at 9 months, is now able to speak full sentences (adequate)
• Social skills- plays with other children (adequate)

Family social history

• 1st born child
• Mother is a househelp, father a carpenter
• No chronic illness history, no history of allergies or asthma
• Live in a 1 bedroom apartment in Pipeline. Has 2 windows, and access to tap
water. Use gas for cooking
• Not an NHIF beneficiary
Review of Systems
• CNS, MSS, GUT unremarkable

Summary
• G.N, 3 yr old female presented with a 4 day
history of productive cough, fast breathing,
hotness of body, and yellowing of the eyes
and skin, and 1 day hx of vomiting and loss of
apetite
 Physical Exam

General Exam
• I found a young girl in FGC, not in obvious respiratory distress, with
an adequate nutritional status.
• On examination- Jaundice present(scleral, palms & feet), Palor
present (conjuctival and palmar) No oedema, No cyanosis, No finger
clubbling, No Dehydration(moist mucus membranes, skin pinch
return 1 sec, cap refill 3 secs, no sunken eyes, radial pulses strong)
• Vitals-temp 36.6(N), resp- 44(H), pulse-152(H), SpO2-94% on room
air
• Arthropometry- Head circumference-51 (N), MUAC- 12.8(at risk),
height- 93cm(N), Weight-11kg (L), WHZ -2SD (moderate)
Systemic exam
Respiratory system
• Inspection No flaring of alae nasae, no LCWI, No intercostal or
suprasternal recessions. no chest wall deformities
• Palpation: trachea central, no tenderness, no masses
• Percussion: resonance over all the lung fields.
• Auscultation: fine crackles in lung bases bilaterally

P/A
• Inspection: moves with respiration, non distended, umbilicus is inverted,
no scars, no visible veins no skin changes.
• Palpation: non-tender. Hepatomegaly with a liver span of 10 cm (average
6-8) and Splenomegaly grade 3 (just above the umbilicus)
• Percussion: Tympanic
• Auscultation: bowel sounds present
CNS
• Alert
• Pupils bilaterally and equally reactive to light
• Neck soft, no meningeal signs
• Normal muscle tone and power

CVS
• Inspection- normoactive precordium
• Palp- apex beat at 4th intercostal, midclavicular line
• Ausc- S1 and S2 heard, no murmurs

MSS
• No joint swelling, tenderness, or warmth
• Normal Range of motion in all joints
Summary 2
Impression
G.N, 3 yr old female presented with
a 4 day history of productive cough
• Severe malaria
and fast breathing, hotness of body,
and yellowing of the eyes and skin,
Ddx
and 1 day hx of vomiting and loss of
apetite. On general exam, there was • Sickle cell disease-
Jaundice up to the level of the feet, hemolytic crisis
Conjunctival and palmar pallor,
• Acute Chest
tachypnea(44) and tachycardia(152).
Weight was 11kg & MUAC was 12.8
Syndrome
(At Risk) On systemic exam, there • Hepatitis
was non tender hepatomegaly of
10.5cm and Splenomegaly (grade 3)
Investigations
• GXM
• FHG- Leukocytosis (16), Low Hb
6.2g/dL, HCT (20%),
thrombocytopenia (114)
• Sickling test- positive
• Hepatitis Ag- A,B,C negative
• BS for mps- no mps seen
• To do Hb electrophoresis on discharge

Others
• RBS, UEC(malnutrition and AKI), CXR
 Management
• Transfused PRBCs 150mls over 4hrs
• IV Xpen 500,000 IU QID 5/7
• IV Gentamicin 75mg OD 5/7
• IV Artesunate- 30mg at 0, 12, 24hrs
• PO AL-1 tablet BD 3/7
• PO Folate- 5mg OD 1/12
• PO Pen V- 125mg BD 1/12
• PO Hydroxyurea 200mg

• Nutritional review
Sickle Cell Disease

(Drepanocytosis)
 Demographics
• Common in individuals of African descent.
• Sickle Cell Disease affects 20-25 million of people globally, of
which 12-15 million live in Africa
• In Kenya;
– In the western region it is estimated that as high as 18% of
children are born with a Sickle Cell Trait and 4.5% will end
up developing SCD.
– In the Nyanza region, it is estimated that about 17%
children are carriers of the trait with 0.6% having SCD
– In the coastal region, using inpatient data, almost 1% of
inpatient children have SCD
 Etiology
• Sickle cell disease is an autosomal
dominant disorder

• Follows spontaneous mutation in the HBB

gene which codes for the β-chain of
Haemoglobin on chromosome 11
• It leads to a single amino acid substitution
in the 6th position of the β-chains (valine
for glutamate) resulting in a new HbS
(rather than HbA)
 Forms of Sickle Cell Disease
• Sickle Cell Anemia (homozygous).
– Inheritance of two sickle cell genes (HbSS).
– More severe form of the disease.
– Lifelong condition requiring management and treatment.
• Sickle Cell Trait (heterozygous).
– Inheritance of one sickle cell gene and one normal gene
(HbAS).
– Usually asymptomatic but can experience symptoms
under extreme conditions.
– Provides some resistance to malaria.
 Pathogenesis
• HbS can't withstand hypoxia; if exposed to low
O2 tensions, HbS polymerizes, causing RBC
distortion and rigidtiy and intravascular
sickling.
• Consequences:
1. Aggregation leading to vascular occlusion due to
higher blood viscosity which initiates thrombosis.
2. Trapping and hemolysis in the reticuloendothelial
system in the spleen and liver.
NORMAL SICKLE
• Disc shaped • Sickle shaped
• Deformable • Rigid
• Lifespan 120 days • 20 days
 Clinical Picture
• Earliest manifestations:
– mild hemolysis by 3 months of age,
– hyposplenism by 5 months,
– initial splenomegaly after 6 months,
– first crisis detected between 6-12 months in about
50% of cases.
– Features of anemia(SOB, pallor, fatigue) & chronic
hemolysis starting after 6 months.
– Renal disorders: proteinuria, nephrotic syndrome,
chronic renal failure
 Crisis Types
• Aplastic
• Hemolytic
• Vaso-occlusive crisis (painful crisis)
• Sequestration crisis
• Infectious crisis
 Haemolytic crisis
• Symptomatic anaemia:
– Fatigue/extreme tiredness or decreased activity or
irritability
– Dyspnoea & Tachypnea
– Palpitations
– Decreased cap refill time
• Increasing jaundice (yellowness of eyes, palms and soles of
feet)
 Vaso-occlusive Crisis
• Due to in vivo sickling leading to vascular
occlusion, ischemia, and infarction.
• Precipitating factors: fever, acidosis,
dehydration, infection, hypoxia(mnemonic DADI)
• Clinical manifestations:
– Painful crisis- bone, muscle, chest, abdominal
– Cerebrovascular accident(MCA)
– Acute chest syndrome,
– Hand and foot syndrome- ischemia of metacarpal
and metatarsal bones, leading to pain and swelling
(dactylitis)
– Renal infarction- manifests as hematuria
– Priapism- due to occlusion of penile sinusoids
causing venous outflow obstruction.
• CVA/Stroke- major complication of SCD which
causes disability.
• Presents as hemiparesis, seizures, CN palsies,
Altered LOC, Aphasia or subtle signs eg.limp
• Acute chest syndrome-life threatening
complication arising due to occlusion of
pulmonary vasculature
• Presents as fever, cough, chest pain, wheezing,
tachypnoea, & SOB with coarse infiltrates on
CXR (similar to pneumonia hence requires
high index of suspicion)
 Sequestration crisis
• Sequestration crisis: sudden pooling of
blood in the spleen or liver due to splenic
vasoconstriction causing pooling of RBCs.
• Clinical signs: acute pallor, hypovolemic
shock and hypotension, acute abdominal
pain with rapidly enlarging
splenomegaly(due to blood
accumulating)
• FHG shows marked fall in Hb level (acute
drop of more than 2g/dL)
• It usually recurs in 50% of patients and
carries a 15% mortality rate (requires
prompt recognition)
Infectious Crisis
• SCD patients have impaired immunity as a result of splenic
dysfunction (fibrosis) leaving them vulnerable to various
organisms.
• Encapsulated organisms i.e, N.menengitidis, H. influenzae, S.
pneumonia & Salmonella spp.
• High index of suspicion required in SCD patients with fever.

Aplastic crisis
• Marked by an acute drop in Hb and a markedly reduced number
of reticulocytes in peripheral blood.
• Platelet and white blood cell counts are generally unaffected
• Usually follows infection by Parvovirus B19 infection (80%)
 Complications of SCD
• Jaundice- unconjugated hyperbilirubinemia
• Galstones- pigment stones due to hemolysis
• Anaemia – chronic hemolysis
• Adenotonsilar hypertrophy- marked hypertrophy occurs to compensate for
loss of lymphoid tissue in the spleen(18% of patients)-causes airway
blockage.
• Bone marrow hyperplasia
• Osteomyelitis- Salmonella
• Leg ulcers-due to increased venous pressure in the legs during vaso-
occlusion and expanded blood volume in the bone marrow.
• Poor weight gain- due to increased caloric requirements i.e bone marrow
hyperactivity and cardiovascular compensation
• Heart failure- due to chronic anemia increasing cardiac activity
• Multiorgan failure- due to thrombosis in vessels supplying vital organs
 Investigations
Lab
• FHG- Anemia Low Hb, Low Hematocrit, high reticulocyte count.
• Peripheral blood film: detect sickle cells, Howell-Jolly bodies
• Sickling test- Na metabisulphite (efficacy after 6 moths of age due to
HbF)
• Hb electrophoresis*: shows HbS (90%) and HbF (2-10%) [principle-HbS
has a higher net electrical charge than HbA hence different
electrophoretic mobility]
Imaging
• Skull Xray- hair on end appearance (hemolytic anemia)
• CXR - coarse infiltrates (Acute chest Syndrome), Cardiomegaly
(ventricular hypertrophy)
• Head CT scan- in CVA
 Treatment
1. Emergency & Chronic transfusion therapy (simple or exchange)
2. Treatment of crises:
Supportive- ABC, remove stop factors
Vaso-occlusive crisis (Including ACS)
– Hydration – 1.5x the Maintainanace requirements
– Exchange transfusion- reduce acute sickling
– Nitric Oxide- potent vasodilator which improves oxygenation (esp in ACS and
CVA)
– Analgesics for pain crises;
• Mild pain- can be treated at home with reassureance, massages,
increased fluid intake and oral analgesics PCM 10-15mg/kg 6 to 8hrly
• Moderate pain – Ibuprofen 5mg/kg TDS/ Diclofenac 1mg/kg TDS
• Severe pain- Oral morphine 0.5mg/kg 3hrly (max 10kg/day)
Sequestration crisis
• Blood transfusion
• Exchange transusion
• Emergency splenectomy if non-refractory
Acute chest Syndrome- admit, maintaon SPO2>95%, emperical Abx
• Infection- Because of a marked incidence of bacterial sepsis and meningitis
and fatal outcomes in under 5s, the following management is recommended:
• All children with sickle cell disease should receive oral Penicillin V prophylaxis
starting at 3–4 months of age (tablets or syrup):
• 62.5 mg BD (up to 1 year)
• 125 mg BD (1–3 years)
• 250 mg BD (3–6 years)

• Vaccination:
• Early diagnosis of infections requires education of the
family to identify a child with fever
• Caregivers should be instructed to seek medical advice
immediately if their child develops a single temperature
greater than 38.0°C for prompt antibiotic treatment.

• Folate therapy is also given:

• <6months- 0.1mg/day
• 1-2yrs- 0.5mg/day
• >2yrs- 1mg/day
 Definitive management
1. Hydroxyurea
• Causes upregulation of HbF. HbF, within the red cell, interferes with
polymerization of HbS, and therefore decreases the propensity of the red cell to
sickle.
• Dosing – starts at 20mg/kg (max 35mg/kg/day) [look out for toxicity –causes
myelosuppression & pancytopenia]
• It therefore;
• Reduces number of VOC crises.
• Reduces incidence of ACS.
• Reduces transfusion needs

2. Hematopoietic Stem Cell Transplantation

3. Gene therapy
Thank you