ABBREVIATIONS

ANA Antinuclear Antibody

BMT Bone Marrow Transplant
ECG Electrocardiography
ECHO Echocardiography
HSCT Haematopoietic Stem Cell Transplant
SCD Sickle Cell Disease
ICU Intensive Care Unit
LDH Lactate Dehydrogenase
NSAIDs Nonsteroidal Anti- Inflammatory Drugs
MRI/MRA/MRV Magnetic Resonance Imaging/AngiographyVenography
PBS Peripheral Blood Smear
HLA Human Leukocyte Antigen
UTH University Teaching Hospital
IVIG Intravenous Immunoglobulin
IBMFS Inherited Bone Marrow Failure Syndrome
TFT Thyroid Function Test
LFT Liver Function Test
FBC Full Blood Count

APLASTIC ANAEMIA

Introduction
The International Agranulocytosis and Aplastic Anaemia Study has defined aplastic anaemia as
haemoglobin 10 g/dL, platelet count 50 x 109/L, granulocytes 1.5 x 109/L, and a bone
marrow biopsy demonstrating a decrease in cellularity and the absence of significant fibrosis or
neoplastic infiltration.
Evaluation
Any evaluation for new onset severe aplastic anaemia (SAA) must start with a thorough history.
A detailed history may identify factors directly causing SAA or may lead to suspicion that the
cytopenia reflects another underlying disease such as an Inherited Bone Marrow Failure
Syndrome (IBMFS).
A thorough physical examination is critical. While some findings, such as pallor or bruising, may
reflect the presence of cytopenias, other specific exam findings may suggest a diagnosis other
than SAA. A non-exhaustive list of examples includes lymphadenopathy, hepatosplenomegaly,
joint swelling, non-petechial rash, icterus, café au lait spots, short stature, weight discordance for
height, abnormal limbs, nails or digits, or other visible congenital anomalies.
To make a proper diagnosis, these evaluations need to be interpreted together with the clinical
presentation. Depending upon the patient characteristics and provider's clinical judgement,
additional evaluations may also be indicated. Patients with presentations not meeting criteria for
idiopathic SAA may warrant a genetic evaluation. Once a diagnosis is made, the patient must be
referred to a tertiary hospital for further management.

Differential diagnosis for aplastic anaemia

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 Acquired Inherited
Infection Bone marrow failure secondary to inherited
● Hepatitis A, B, C. syndromes
● CMV ● Fanconi anaemia
● ● Dyskeratosis congenita/telomere biology
● HIV disorders
● Shwachman Diamond syndrome
Medications/ Toxins MDS secondary to haematopoietic malignancy
● Benzenes, chloramphenicol predisposition syndrome
● Cytotoxic medications
● Ionizing radiation
Nutritional deficiencies Pancytopenia associated with primary
● Zinc immunodeficiency
● Copper,
● Vitamin B12
● Folate
Myelodysplastic Syndrome (MDS)
Rheumatologic disorders
Paroxysmal nocturnal Haemoglobinuria (PNH)

Newly diagnosed children should be referred promptly to a tertiary institution/ paediatric

haematology unit for urgent work- up and treatment. Those admitted will begin their complete
work- up as follows:

Work- up
Blood work related to acquired aplastic anaemia:
1. FBC, differential, peripheral smear, reticulocyte count
2. Hb electrophoresis
3. Bone marrow aspirate and trephine biopsy (BMAT), including cytogenetics. Note
BMAT is done under anaesthesia in theatre. Liaise with paediatric anaesthesia for
pre- operative assessment.
4. Liver enzymes and function tests- ALT, AST, alkaline phosphatase, bilirubin (conjugated
& unconjugated), GGT, albumin, total protein, INR/PTT/fibrinogen.
5. Electrolytes (Na, K, Cl), calcium, phosphate, magnesium.
6. Renal function test- urea, creatinine
7. Direct Antiglobulin Test (DAT), haptoglobin, LDH, ESR.
8. Iron studies- serum iron, ferritin, transferrin
9. Viral studies- Hepatitis A, B and C, HIV, and CMV.
10. Anti- nuclear antibody (ANA), anti- double stranded DNA, rheumatoid factor (RF).
11. Complement C3 & C4, CRP, CH50, immunoglobulins (IgG, IgA, IgM)
12. Serum vitamin B12, and serum and red cell folate
13. Referral for HLA typing
14. Group and cross match

Blood work related to inherited aplastic anaemia:

1. Peripheral blood for chromosomal breakage analysis to exclude Fanconi Anaemia.
2. Flow cytometry for CD55/CD59 to exclude Paroxysmal Nocturnal Haemoglobinuria
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 3. Peripheral blood to test exon 2 of SBDS gene to exclude Shwachman- Diamond
Syndrome.
4. Telomere length testing to exclude Dyskeratosis Congenita.
5. Abdominal ultrasound as screen for congenital anomalies that may related to an inherited
bone marrow failure syndrome.
6. Referral for HLA typing.

Treatment
Supportive measures:
1. Transfusion support.
Transfuse packed red blood cells as needed for clinical symptoms related to anaemia and/or
to maintain haemoglobin levels > 7 g/dL. Transfuse platelets as needed for clinical
indications of bleeding and/or to maintain platelet counts > 10 x 109/L when patient is well
and > 20 x 109/L when febrile.
2. Management of fever.
In the event of fever and neutropenia (neutrophil counts 0.5 x 109/L) for more than 3- 5
days despite antibiotic therapy, then initiation of neupogen should be considered. 3 Neupogen
dose is 5 mcg/kg/dose subcutaneously daily. Discontinue if there is no significant increase in
neutrophil count within one week.
In case of severe infection, or recurrent bacterial or fungal infection, or clinical instability the
neupogen should be increased by 5- 10 mcg/kg/dose every 3- 5 days, up to a maximum of 60
mcg/kg/dose or 1,500 mcg/day whichever is less.
3. Infection Prevention
a. Pneumocystis Jirovecii Pneumonia (PJP) Prophylaxis: Prophylaxis should be started
on initiation of immunosuppressive therapy, and discontinued once patient has responded
to immunosuppressive therapy and has been discontinued.
Cotrimoxazole is not an option for PJP prophylaxis due to bone marrow
suppression with its use.
Dapsone 4 mg/kg/day (maximum 200 mg/dose) PO once/week. Contraindicated in
patients with G6PD deficiency. Obtain baseline methaemoglobin level prior to starting
the drug.
b. Fungal Prophylaxis: Fluconazole prophylaxis for patients with severe neutropenia
(neutrophil count < 0.2 x 109/L). Fluconazole dose is 3 mg/kg/day IV/PO once daily
(maximum 400 mg/day). Due to the interaction with cyclosporine, discuss potential need
to adjust doses with pharmacist.

Treatment of patients with a matched sibling donor for HSCT:

A matched sibling donor for Hematopoietic Stem Cell Transplant (HSCT) is the first line of
therapy for patients with acquired severe and very severe aplastic anaemia and IBMFS resulting
in approximately 90% cure rate. HLA-typing of the patient and all immediately related family
members (parents and siblings) is carried out as part of the initial work-up.
Arrangements must be made through the Ad-hoc committee at the University Teaching Hospital
(UTHs)- Children’s Hospital for HSCT abroad.

Treatment of patients without a matched sibling donor for (HSCT)- Immunosuppressive

therapy:

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Immunosuppressive therapy (IST) should be initiated as soon as possible. This requires
admission to the paediatric haematology inpatient unit. Baseline blood work to be done within 24
hours of admission:
1. FBC, differential, retic count, and PBS
2. Liver enzymes- ALT, AST, Alk Phosphatase, bilirubin (Unconjugated & conjugated),
GGT
3. Liver Function Tests
4. Renal function tests- urea and creatinine
5. Na, K, Cl, Mg, Ca, Phos, LDH, and urate

Medications for immunosuppressive therapy

IST Regime Dose Notes
Anti-thymocyte 40 mg/kg/dose IV over 6 hours To be infused over a minimum of 6 hours;
Globulin (ATG) daily x 4 days infusion may be prolonged up to a
(ATGAM® = equine maximum of 12 hours
ATG)
Prednisolone 1 mg/kg/dose (Max 40 mg/dose) ● Start 3 hours before ATG
PO two times daily x 7 days ● Taper slowly over 3 weeks once ATG
therapy completed.
Cyclosporine (CsA) 5 mg/kg/dose (max 250 ● Trough CsA concentration to be
mg/dose) PO q12h for 6 months drawn on day 3 of therapy
after maximal response is ● Adjust dose to maintain whole blood
achieved, then taper over 6 serum concentration between 150 -
months. 200 mcg/L
Pre- medication Dose Notes
Paracetamol 15 mg/kg (max 1000mg/dose) Dose limit of 75 mg/kg/day or 4 g/day,
PO pre- ATG and then q6h PRN whichever is less.
Diphenhydramine 1 mg/kg/dose (max 50 mg/dose)
PO/IV pre-ATG and then q6h
PRN

Pethidine 1 mg/kg/dose (max 50 mg/dose)

IM q6h PRN for rigors

If there is no response at 3-6 months’ post-initial IST, then consideration should be made for a
BMT from an unrelated HLA matched hematopoietic stem cell donor. A thorough discussion
must occur with the parents/guardian and BMT team regarding potential donors and the
approach to therapy that will yield the best possible outcome.

Management of possible complications secondary to medications

Medication Complication Treatment/Management

ATG Serum sickness Serum sickness post ATG is a type III hypersensitivity (immune
complex- mediated) reaction that results due to the injection of
foreign protein into a patient. Symptoms & signs may include:

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 fever, malaise, cutaneous eruptions (especially urticaria),
arthralgias/arthritis, GI complaints (abdominal pain, nausea,
vomiting, diarrhoea), headache, myalgia, blurred vision,
dyspnea/wheezing and lymphadenopathy starting usually 1-2
weeks post-ATG administration. Clinical recovery can take
between 1-4 weeks. Treatment: Continue prednisolone dose for
1 week, and Diphenhydramine 1mg/kg/dose (max 50 mg/ dose)
PO/IV q6h PRN.
Anaphylaxis Stop ATG infusion immediately. See anaphylaxis treatment
protocol

Cyclosporine Hypomagnesemia Supplement with oral magnesium.

Provide patient/family with magnesium diet.

Hypertension If SBP and/or DBP >95th %ile for age and height on 2 separate
occasions 15 minutes apart, & on > 2 consecutive days, start
amlodipine dosed as per Paediatric dosing schedule.

Nephrotoxicity If serum creatinine is elevated to 1.5 x baseline, increase fluid

intake to 1.5 x maintenance, and consider reducing cyclosporine
target trough concentration after discussion with pharmacist.

Prednisolone Gastritis/ Initiate omeprazole if symptomatic while receiving

Heartburn prednisolone.

Hypertension See cyclosporine above

Follow- up Post Immunosuppressive Therapy

Once the patient has completed cyclosporine taper, close monitoring during the first two (2)
years post- therapy is important to assess for symptoms and signs of relapse. Should the patient
begin to exhibit clinical and/or haematological changes during post- therapy follow- up, a BMA
and biopsy may be necessary.

Follow- up schedule

Frequency of visits Tests/Bloodwork

Every visit:

● Vital signs, height, weight,

● FBC, differential, retic count, smear
● 1 month after stopping
Year 1 – Year 2 cyclosporine and then
Every 6 months*:
● Every 2-4 months*
● Urea, creatinine
● LFTs (ALT, AST, alk phosph, bili –
unconjugated & conjugated)

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 Every visit:

● Vital signs, height, weightCBC, differential,

retic count, smear
Year 2 – Year 5 ● Every 6 months*
Annually*:

● Urea, creatinine
● LFTs (ALT, AST, alk phosph, bili –
unconjugated & conjugated)

● Vital signs, height, weight,

● FBC, differential, retic count, smear
Year 5 + ● Annually* ● urea, creatinine
● LFTs (ALT, AST, alk phosph, bili – unconjugated
& conjugated)

*May be completed more frequently if clinically indicated.

Immunizations
Patients can continue to receive recommended scheduled inactivated virus immunizations. There
is a possibility that patients may not mount an appropriate immune response to immunization,
thus re-immunization may be necessary once they are no longer immunosuppressed.

Live attenuated viral vaccines, such as the MMR, are contraindicated while patients are on
immunosuppressive therapy due to the increased risk of developing disease caused by the
vaccine.

References
1. Davies, J. K. & Guinan, E. C. An update on the management of severe idiopathic aplastic
anemia in children, British Journal of Haematology, 136, pp. 549-564, 2007.
2. Young NS, Kaufman DW. The epidemiology of acquired aplastic anemia Haematologica.
2008;93(4):489-492.
3. Marsh, J. C. W., Ball, S. E., Cavenagh, J., Darbyshire, P., Doak, I., Gordon-Smith, E. C.,
Keidan, J., Laurie, A., Martin, A., Mercieca, J., Killick, S. B., Stewart, R., Yin, J. A. L.,
& Writing Group: British Committee for Standards in Haematology (2009). Guidelines
for the diagnosis and management of aplastic anemia, British Journal of Haematology,
147, pp. 43-70.

HAEMOPHILIA

Introduction
Haemophilia refers to inherited bleeding disorders caused by deficiency of specific coagulation
factors. Haemophilia A is caused by coagulation factor VIII (FVIII) deficiency, haemophilia B
by deficiency of coagulation factor IX (FIX), and haemophilia C by deficiency of coagulation
factor XI.

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These clotting factor deficiencies are caused by recessive mutationsof the respective clotting
factor genes. As the recessive mutant FVIII and FIX genes are located on the X chromosome,
both haemophilia A and haemophilia B are inherited in an X-linked pattern. Consequently, in
these conditions, males are affected and females are carriers of haemophilia. Both diseases have
the same clinical presentation, so their specific diagnosis must be established by factor assay.
The combined prevalence of both haemophilia A and B has been estimated as approximately 1 in
5 000 live male births. Haemophilia C is an autosomally inherited condition, uncommon in the
general population of Zambia, and will therefore not be discussed further in this guideline.

Clinical Features
● Many have spontaneous or provoked bleeding
● Large or deep bruises
● Joint pain and swelling due to bleeding within them
● Excessive bleeding following minor injury or surgery
● Easy bruising
● Menorrhagia
● Nose bleeds
● Spontaneous nose bleeds
● Unexplained bleeding and haematuria or haematochezia
● Intracranial haemorrhage

Diagnostic Tests
● Prolonged APTT with a normal PT and normal platelet count is suggestive
● Confirm with a Factor VIII or Factor IX assay:
Classification of haemophilia
Severity Factor level
Severe < 1%
Moderate 1- 4 %
Mild 5- 40 %
NOTE: Normal factor level ranges from 50- 200%

● Recommended weekly factor prophylaxis to prevent bleeds is 25- 40IU/ kg or more

depending on clinical situation.

Treatment of bleeding in haemophilia

Manage people with haemophilia at or under the supervision of a haemophilia comprehensive
care centre.

Patients with haemophilia can have spontaneous bleeding and/or excessive bleeding with mild
trauma. It is imperative to treat haemophilia patients with factor within 30 minutes of
presentation first and then consider diagnostic testing later.

Sites of bleeding in Haemophilia

Non- life or non- limb- threatening bleeds Life- or organ- threatening bleeds
Joints Intracranial
Muscles Muscle compartment

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Easy bruising Neck/throat
Mucosal bleeding (epistaxis, gingival) Massive gastrointestinal
Gastrointestinal Genitourinary tract

● Factor replacement
o Factor VIII deficiency (Haemophilia A)
▪ 1 unit/kg increases Factor VIII activity by 2%
▪ Give 30 units/kg of Factor VIII for an acute minor bleed
▪ Give 50 units/kg of Factor VIII for an acute major bleed
▪ After initial dose, discuss treatment plan with paediatric haematology unit.
Half- life of Factor VIII is 8- 12 hours. Major bleed will likely need 8- 12-
hour dosing.

o Factor IX deficiency (Haemophilia B)

▪ 1 unit/kg increases Factor IX activity by 1%
▪ Give 50 units/kg of Factor IX for an acute minor bleed
▪ Give 100 units/kg of Factor IX for an acute major bleed
▪ After initial dose, discuss treatment plan with paediatric haematology unit.
Half- life of Factor IX is 18- 24 hours. Major bleed will likely need at least
24-hour dosing.
o It is important to round up both Factor VIII and IX to a unit vial dose whenever
possible to avoid wastage.
o Important: Where Factor VIII or Factor IX is unavailable or not immediately
available in emergency situations, Call blood bank immediately and order Fresh
Frozen Plasma (FFP) at 10- 20 mL/kg IV to run over 1 hour.

● Supportive care (PRICE)

o Protection
o Rest/Replacement
o Ice/Immobilization
o Compression
o Elevation
● Add Tranexamic acid (antifibrinolytic- prevents clot breakdown) 10mg /kg 8 hourly IV
(or 15- 25 mg/kg orally) for mucocutaneous (mouth, nose) bleeding. Contraindicated in
urinary tract bleeds.

● Pain management
o Pain in people with haemophilia has multiple causes, and these include:
▪ Joint capsular stretching as a result of haemarthrosis.
▪ Haemophilic arthropathy
▪ Compartment syndrome.

8
 o The goals of pain management include:
▪ To remove pain completely without increasing the risk of bleeding
▪ To improve the patient’s quality of life.
o COX- 2 inhibitors (such as tramadol) are favoured largely owing to their
favourable side- effect profile, analgesic effects, anti- inflammatory effects and
anti- angiogenic effects.
o Aspirin and other antiplatelet agents should be avoided.
o Analgesia requiring intramuscular injection should also be avoided.

● For patients with a confirmed diagnosis of haemophilia, offer to enrol in the World
Bleeding Disorder Registry (WBDR).
● Surgery
o For patients with haemophilia requiring elective or emergency surgery, discuss
this with paediatric haematologist.
● Vaccinations
o Vaccinate all individuals with haemophilia with appropriate vaccines. Standard
vaccines for children can be given without factor concentrate prophylaxis.
o An ice pack can be applied to the injection area for 5 minutes before injection.
o The smallest gauge needle available (usually 25- 27 gauge) should be used.
o Application of ice and prolonged pressure for 10 minutes is recommended after
administration of the vaccine.
o Prophylactic Clotting Factor Concentrate (CFC) cover for irritant vaccines such as
tetanus should be given prior to vaccination.
● For routine clinic follow-up, see the table below.
AGE VISIT LAB TESTS ADDITIONAL CHECKS
FREQUENCY
0-6 3 months ● Blood group at first visit. ● Demonstrate
years ● FBC, diff, retic count ● Emergency preparedness.
every visit. ● Vaccination check
● Serum ferritin annually. ● Counselling about Haemophilia.
● Hepatitis B/Hepatitis C/
HIV serology annually.
● HJHS annually.

6- 16 6 months ● Blood group at first visit. ● Assess readiness for self-infusion.

years ● FBC, diff, retic count ● Emergency preparedness.
every visit ● At 12 years of age, begin transition
● Hepatitis B/HIV serology assessments.
annually.
● Serum ferritin annually.
● HJHS annually.

References

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 1. Evidence- based management of sickle cell disease, expert panel report, 2014.
Guidelines for the management of haemophilia 2nd edition. 2014. World Federation of
haemophilia. Blackwell Publishing.
2. Zambian National Guidelines for the management of haemophilia. Ministry of
Health. 2020.

SICKLE CELL DISEASE

1.0 INTRODUCTION
Sickle cell disease is an inherited (genetic) disease that affects the haemoglobin in the red blood
cells. Haemoglobin is the protein in red blood cells that carries oxygen to every part of the body.
SCD causes red blood cells to “sickle” (change from a normal doughnut shape to a crescent mon
shape).

2.0 ROUTINE MEDICATIONS

● Folic acid supplementation

o Patients with chronic haemolysis as with SCD benefit from folic acid
supplementation.
o Give 5mg OD PO for all ages.
o For infants, the tablet can be crushed into a suspension for ease of administration.
● Hydroxyurea
o Mechanism: Hydroxyurea is an antineoplastic that may cause inhibition of DNA
synthesis by acting as a ribonucleotide reductase inhibitor. It increases fetal
haemoglobin, reduces neutrophils, alters adhesion of red blood cells to endothelium,
increasing water content of red blood cells and increases deformability of sickled
cells.
o Indication: All Hb SS or Hb S beta 0 thalassaemia patients  9 months of age should
be counselled on the potential benefits and risks of chronic hydroxyurea therapy, and
encouraged to begin taking it.
o Exclusions: acute liver disease, history of severe hydroxyurea toxicity or
hypersensitivity, pregnancy or sexually active and unwillingness to use contraception.
o Baseline investigations prior to initiating hydroxyurea treatment: FBC with
differential count, reticulocyte count, Hb electrophoresis or High Performance Liquid
Chromatography (HLPC), (with quantitative Hb F%, & Hb S%), Chemistry profile,
Liver Function Tests (AST, ALT), renal function tests (urea, creatinine).
o Patients on hydroxyurea shall have Hb electrophoresis done every 6 months for
monitoring.

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 o Consult with paediatric haematologist for appropriate work- up before initiating
a patient on hydroxyurea.

o Dosing:
▪ Starting dosage for infants and children is 20 mg/kg/day given as a single
daily dose.
▪ Monitor FBC with differential and reticulocyte count at least every 4 weeks
when adjusting dosage.
▪ If dose escalation is warranted based on clinical and laboratory findings,
proceed as follows- increase dose by 5 mg/kg/day every 8- 12 weeks.
▪ Increase dose until absolute neutrophil count is 2, 000- 4, 000/L (mild
myelosuppression) is achieved or up to a maximum tolerated dose (MTD) of
35mg/kg/day dose achieved.
▪ Once a stable dose is established, laboratory safety monitoring should include
FBC with differential, reticulocyte count, and platelet count every 2- 3
months.
▪ People should be reminded that the effectiveness of hydroxyurea depends on
their adherence to daily dosing. They should be counselled not to double up
doses if a dose is missed.
▪ A clinical response to treatment with hydroxyurea may take 3- 6 months.
Monitor RBC MCV and Hb F levels for evidence of consistent or progressive
laboratory response.
▪ If neutrophil count < 2.0 x 109/L, or retic count < 80 x 1012/L, or platelets < 80
x 109/L or Haemoglobin < 5 g/dL, discontinue hydroxyurea until counts
recover (usually for 5- 7 days) and repeat FBC. If FBC returns to baseline,
restart at same dose.
▪ Liquid formulation can be prepared by compounding pharmacy using
published guideline. The liquid formulation expires after 2 weeks.
▪ Hydroxyurea therapy should be continued during hospitalizations or illness.
● Malaria prophylaxis
o Deltaprim to all patients with sickle cell anaemia. A tablet contains pyrimethamine at
12.5 mg and dapsone at 100 mg.
o Dosing:

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 ▪ Infancy up to 3 years of age ¼ tablet once weekly PO,
▪ 3- 10 years old ½ tablet once weekly PO and
▪ Over 10 years old 1 tablet once weekly PO.
In event of allergy to deltaprim, use dapsone once weekly PO.
● Penicillin prophylaxis
o Patients should be receiving penicillin prophylaxis
▪ Penicillin V 125 mg BD PO daily for 2 months- 3 years
▪ Penicillin V 250mg BD PO daily for > 3 years.
▪ Substitute with erythromycin if penicillin hypersensitivity present.
o Discontinuing penicillin prophylaxis can be considered for patients age 5 years and
older who meet BOTH criteria:
▪ Patients without prior history of documented pneumococcal infection
▪ Patients who have received 1 dose of PPV (pneumococcal 23) and appropriate
PCV 13 doses.
▪ Never had a splenectomy.
● Diagnostics
o Ideally, haemoglobin (Hb) electrophoresis or High Performance Liquid
Chromatography (HPLC) should be sent after 6- 12 months of age as long as there
has not been a red blood cell transfusion in the previous 3 months.
o For infants 0- 3 months of age born in Lusaka or Ndola, they can be referred to the
University Teaching Hospitals (UTHs)- Children’s Hospital or Arthur Davison
Children’s Hospital respectively for newborn screening for SCD.
● For routine clinic follow up, see the schedule below.
AGE VISIT LAB TESTS ADDITIONAL INFORAMATION
FREQUENCY

0-2 years 3 months ● Hb electrophoresis ● Vaccination check

● Blood group ● Antibiotic prophylaxis
● FBC, diff, retic count ● Demonstrate palpation of spleen
every visit ● Hydroxyurea (start after age 9 months)
● Vitals: SpO2, weight, height, every visit

2- 5 6 months ● FBC, retic count every ● Vaccination check.

years visit ● Pneumococcal polysaccharide vaccine
● Bili, RFTs, LFTs annually (PPV23) should be administered as

12
 ● HIV, Hepatitis B soon as 24 months of age for
● TCD annually supplemental protection.
● Antibiotic check
● Hydroxyurea
● Vitals: SpO2, weight, height, every visit

5- 12 6 months • FBC, retic count every • Vitals, SpO2, weight, height every visit
years visit
• Hydroxyurea
• Bili, urinalysis, RFTs,
LFTs annually • Ophthalmology screen at age 10.

• HIV, Hepatitis B annually • Echocardiogram with PHTN screen:

Only when symptomatic
• Brain MRI/MRA/MRV
(baseline scan) at age 8. • PFTs at age 10, if normal, again when
symptomatic.
• TCD annually
• Linkages

12- 16 6 months • FBC, retic count every • Vitals, SpO2, weight, height every visit
years visit
• Hydroxyurea
• Bili, urinalysis, RFTs,
LFTs annually • Ophthalmology screen annually

• HIV, Hepatitis B annually • Echocardiogram: Only when

symptomatic

• PFTs

• Linkages

• Transition assessment

3.0 PAIN CRISIS

Caused by ischaemic tissue injury from the obstruction of blood flow by sickled red
blood cells. Reduced blood flow causes hypoxia and acidosis. Infection, fever, acidosis,
hypoxia, stress, dehydration, sleep apnoea, and exposure to extremes of temperature can
precipitate crisis.
3.1 Clinical features
Common sites of pain include bone (extremities, hand/foot syndrome, back) and
abdominal pain. Bone pain, the most common type of VOC, may or may not be
accompanied by swelling, low-grade fever, redness, and warmth. It may be symmetrical,
asymmetrical, or migratory. Dactylitis is a common presentation in infants and toddlers;
back and abdominal pain are more common in older children. Abdominal pain in children
with sickle cell disease is usually a simple VOC

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Diagnostics
▪ FBC with differential and reticulocyte count (anaemia and reticulocytosis
typical).
▪ Peripheral smear: sickled red blood cells, red blood cell fragments, Howell-
Jolly bodies (splenic infarction).
▪ Total bilirubin and LDH (hyperbilirubinaemia and elevated LDH due to
haemolysis).

3.3 Management
▪ Hospital admission is mandatory if pain control with oral analgesics is not
adequate, or if other problems (such as fever or dehydration) exist.
▪ Patient should receive analgesia 30 minutes within hospital arrival.
▪ Assess severity of pain. See appendix 1.
▪ If in mild pain, give paracetamol 15 mg/kg with NSAIDs (E.g., Ibuprofen 10
mg/kg with food given 3 times a day). Maximum 30 mg/kg per day.
▪ If in moderate pain give or add tramadol 50- 100 mg orally 4- 6 hourly, for
children > 12 years of age, adjusted according to response. Usual maximum
400 mg/ 24 hours.
▪ If in severe pain give or add opioid IV or oral morphine. For IV morphine,
give 0.1 mg/ kg 4 hourly adjusted according to response. For oral morphine,
give 0.2- 0.3 mg/kg (maximum per dose 10 mg) 4 hourly, adjusted according
to response.

14
 WHO step ladder management of pain
▪ For patients on morphine, give stool softener (e.g. lactulose) unless the child
has diarrhoea.
▪ Hydration: 1.5 x daily maintenance IV fluid in 24 hours, if no
cardiopulmonary compromise.
▪ The fluid of choice is 5% dextrose in normal saline (DNS).
▪ Do not give much fluid in patients with ACS, severe acute anaemia, stroke or
acute splenic sequestration- There is a risk of cerebral or pulmonary oedema.
In these cases, use 2/3 of maintenance fluid.
▪ Monitors vitals, and assess for improvement of symptoms.
▪ Rest and heat to the area of pain; avoid cold as this can worsen pain.
Discharge criteria
● Patient is tolerating fluids and medications by month, pain control is adequate with no
medications, and concurrent problems are resolved.
4.0 PRIAPISM
Is a sustained, unwanted painful erection unrelated to sexual stimulation and unrelieved
by ejaculation. Affects ~35% of boys & men but frequently understated. Prompt
recognition and immediate initiation of conservative medical management may lead to
penis returning to flaccid state & limit need for aggressive & invasive intervention.

4.1 Clinical features

▪ Document onset time of onset. Onset usually occurs during sleep, when
relative oxygenation decreases.

15
 ▪ Erection lasting more than four hours unrelated to sexual interest or
stimulation.
▪ Rigid penile shaft, but the tip of penis (glans) is soft.
▪ Progressively worsening penile pain
▪ No evidence of trauma.

4.2 Laboratory Tests

▪ FBC with differential and reticulocyte count
▪ Hb Electrophoresis***
▪ Group and cross match
▪ Urinalysis and culture
▪ Blood culture if febrile
4.3 Management
▪ Rapid triage- place immediately into examination room & establish
intravenous access.
▪ Hydration: 1.5 x maintenance in 24 hours, if no cardiopulmonary
compromise. The fluid of choice is 5% dextrose in normal saline (DNS). If
DNS is not available, refer to the fluid guidelines.
▪ Pain control: Paracetamol + NSAIDs. Escalate to opioids if severe (See Pain
Control section).
▪ Benefit in voiding or having a warm shower or bath to improve blood
circulation.
▪ Maintain oxygen saturation above 95% (if the patient is hypoxic).
▪ There is no RCT for either simple or exchange transfusion in acute priapism
and variable responses are described in the literature. Patients who require
shunt procedures under general anaesthesia may require simple transfusion
prior to anaesthesia if they have Hb below 9g/dL. Blood transfusion should be
considered when acute priapism does not settle with conservative
management and prior to surgery.
▪ The recommended treatment for priapism that does not settle with
conservative treatment presenting at < 48 hours is penile aspiration of the
stagnant ischaemic blood to decompress the corpora cavernosum.
▪ This is best performed with a 19-gauge needle through the glans or laterally
from the penile shaft. It can be performed under local anaesthetic in the
Emergency Department after a penile block by a urologist.

16
 ▪ Discharge if priapism is resolving, child is taking fluids & medications orally,
is afebrile, and pain relief is adequate.
▪ Commence hydroxyurea as per protocol.
▪ Consider chronic phosphodiesterase type 5 (PDE5) inhibitor therapy such as
Sildenafil in patients with recurrent priapism.
▪ Patients with recurrent episodes of acute priapism will usually employ self-
management techniques at home including exercise, hydration and urination
and they will usually be prescribed an alpha adrenergic agent.
▪ Joint urology/haematology follow up.
5.0 ACUTE SPLENIC SEQUESTRATION
Sudden onset enlargement of the spleen and reduction in Hb concentration by at least 2
g/dL below the baseline value. Splenic pooling of a large amount of blood and platelets
Typically occurs in children with Hb SS between the age of 6 months and 5 years.

5.1 Clinical Features

▪ Sudden onset asthenia
▪ Increased fussiness
▪ Thirstiness
▪ Decreased activity (lethargy)
▪ Acute anaemia (pallor, tachycardia, tachypnoea, frank cardiovascular
collapse);
▪ Splenomegaly (pain in the left upper quadrant and abdominal distension).

5.2 Diagnostic Tests

▪ FBC with differential and reticulocyte count
▪ Group and cross match
▪ Note: Imaging is not essential.
5.3 Management
▪ Transfuse with pRBC urgently with goal back to baseline Hb. (Notify blood
bank).
▪ Generally, transfuse with 10mL/kg packed red blood cells as patient is at risk
of auto- transfusion (sequestered blood leaving the spleen).
▪ If in hypovolemic shock, manage for shock with guidance of senior
present. Refer to management of hypovolemic shock.
▪ Avoid aggressive splenic palpation to prevent splenic rupture.
▪ Usually resolves within 2- 5 days.
▪ In consultation with haematologist, address the performance and timing of
splenectomy to prevent recurrence.

6.0 ACUTE CHEST SYNDROME (ACS)/PNEUMONIA

17
New infiltrate on CXR+ any one of the following:
● Temp > 38.5
● Cough
● Wheezing
● Tachypnoea
● Chest pain
Mostly commonly in the 2 to 4-year olds. Life threatening lung infarction. Occurs in 10-
20% of hospitalized patients with SCD. Usually 1-3 days after admission for severe
VOC.
6.1 Clinical Features
o Fever
o Cough
o Excruciating chest pain
o Shortness of breath
o Low oxygen saturation
o Often precipitated by a lung infection
o Low O2 leads to further sickling of red cells, thus exacerbating pulmonary and
systemic hypoxaemia, sickling & VOC.
6.2 Diagnostic Tests
▪ FBC with differential and reticulocyte count
▪ C- reactive protein
▪ Arterial blood gases
▪ Group and cross match
▪ Hb electrophoresis
▪ LFTs
▪ Chemistries
▪ Blood culture
▪ Total bilirubin and/or Lactate dehydrogenase (LDH).
▪ CXR- PA and lateral view (NOTE: 60% of children with ACS will have an
infiltrate on CXR but a normal pulmonary exam.
6.3 Management
▪ Hydration: IVF at 2/3 maintenance maximum depending on oral intake. Can
decrease or discontinue IVF if taking enough PO fluids to meet daily maintenance
goal.
▪ Antibiotics for severe pneumonia: Cefotaxime or ceftriaxone + Erythromycin or
azithromycin.
▪ Incentive spirometry is indicated for older children with chest or back pain
▪ Over- hydration can lead to pulmonary oedema and worsen acute chest syndrome.
▪ Pain management: be cautions with narcotics but do not withhold. Balance
between pain control and sedation as either may lead to respiratory distress.
Narcotics can lead to hypoventilation and worsen acute chest syndrome.

18
 ▪ Respiratory care: oxygen therapy with pulse oximetry monitoring.
▪ Blood transfusion: 10- 15mL/kg pRBC if significant anaemia (Hb <5g/dL or if
Hb drops <2 g/dL from baseline), significant hypoxia, or worsening respiratory
status.
6.4 Discharge criteria
● The child does not require supplemental oxygen, has been afebrile for at least 24
hours, the child is taking fluids and medications by mouth, pain control is
adequate with PO medications, and concurrent problems are resolved.

7.0 STROKE
Rapidly developing clinical signs of focal (or global) disturbance of cerebral function,
lasting > 24 hours or leading to death, of vascular origin. Occurs in 10- 15% of children
with sickle cell disease. Peak age of onset is 2- 5 years.
7.1 Clinical features
▪ Hemiparesis
▪ Facial weakness
▪ severe headache (w/without associated vomiting)
▪ Visual and language disturbances
▪ Seizures (especially focal seizure)
▪ Altered sensation, behaviour and mental status
▪ Coma
7.2 Diagnostics Tests
▪ FBC with differential and reticulocyte count
▪ Blood glucose
▪ RDT for malaria/MPS
▪ Serum electrolytes
▪ Hb electrophoresis
▪ Group and cross match
▪ Emergent CT scan or MRI/MRA/MRV (where available).
▪ NOTE contrast may exacerbate sickling. Discuss using contrast with
paediatric haematologist on call.
7.3 Management
▪ High flow oxygen
▪ Monitor Glasgow Coma Scale (GCS) and vitals regularly
▪ Control seizures if present
▪ Look for signs of raised ICP and refer to neurology section on stroke.
▪ Urgent blood transfusion at 10mL/kg is recommended (NOTE exchange
transfusion is preferred management where available) to target Hb S < 30%.
▪ Patients presenting with suspect transient ischaemic attack (TIA) or stroke
should have urgent neuroimaging.
▪ Commence on hydroxyurea.
▪ Enrol in chronic monthly blood transfusion protocol (see National SCD
management guidelines).

19
 ▪ For patients on chronic monthly transfusion, monitor for iron overload.
▪ Never exceed a haematocrit of 30%; risk of hyperviscosity.

8.0 SICKLE CELL DISEASE WITH INFECTION/FEVER

Infection is a major complication of SCD, causing morbidity and mortality. Many
children with sickle cell anaemia have significant haemolytic anaemia and impaired
splenic function. The spleen’s phagocytic function is markedly reduced, putting them at
risk of overwhelming septicaemia.

8.1 Common pathogens (encapsulated bacteria)

o S. pneumoniae
o H. influenzae type b
o E. coli
o Salmonella
o Mycoplasma pneumoniae
o Chlamydia pneumoniae
o Strep pyogenes
o Staph aureus
o Neisseria meningitis
8.2 Diagnostic Tests
o FBC with differential and reticulocyte count
o RDT for malaria or Malaria Parasite Slide (MPS)
o Group and save
o Total bilirubin and/or LDH
o Urinalysis
o Blood culture
o CXR
o When clinically indicated- blood chemistries, urine culture, stool culture, lumbar
puncture and evaluation for osteomyelitis.

8.3 Treatment
● Admit for intravenous antibiotic if any of the following is found: age < 1yr, temperature
>38°C, toxic or ill- appearing patient, history of pneumonia, pulse oximetry reading <90%,
on room air, Hb <6 g/dL, WBC <5, 000/mm 3 or > 30, 000/mm3, platelet count < 100,
000/mm3.
● Oxygen if indicated.
● Blood transfusion if Hb < 5 g/dL.
● Hydration
● Start gram- negative rod coverage with intravenous cephalosporin such as ceftriaxone OR
cefotaxime for 7- 10 days.
● Consider Ciprofloxacin for suspected Salmonella osteomyelitis.

20
● Patient with ACS/severe pneumonia, add erythromycin 50mg/kg/day 6 hourly/ or
azithromycin 10 mg/kg daily.
● Anti-pyretic such as paracetamol.

9. SICKLE CELL CARDIOMYOPATHY

Due to the hyperdynamic status of a child living with SCD, they are at increased risk of
developing restrictive cardiomyopathy characterized by diastolic dysfunction, left atrial
dilation and normal systolic function. This results in mild, secondary pulmonary venous
hypertension and elevated tricuspid regurgitant jet velocity. Systolic dysfunction is very
uncommon

Clinical features of Sickle cell cardiomyopathy include:

● Asymptomatic
● Tachycardia
● Galloping Heart sounds
● Loud P2 due to pulmonary hypertension
Anti- failure medication is not prescribed for cardiomyopathy, unless or otherwise guided by
physical assessment, ECHO and chest X- ray. In the presence of high output failure due to severe
anaemia, Red Cell blood transfusion is used to treat the cardiac failure. Prolonged use of loop
diuretics is not advised as it may lead to dehydration of the patient, which may trigger a VOC. If
the patient is otherwise asymptomatic for cardiac failure, the patient may have ECHO screening
done annually.

10. OSTEOMYELITIS
Acute or chronic bone infection affecting the metaphysis of bone. The commonest site of
Osteomyelitis is usually occurring in the lower limbs, especially the Tibia. It is important not
to miss the acute stage of osteomyelitis as this helps prevent serious long-term orthopaedic
sequel caused by chronic osteomyelitis. Also note that it is very difficult to distinguish
between acute osteomyelitis and bone infarctions caused by VOCs. A high index of suspicion
from history, and thorough work -up is important.

Osteomyelitis can be classified, depending on the duration and presentation, into:

● Acute
● post-acute
● chronic
Subacute osteomyelitis should be distinguished from post- acute osteomyelitis as this is a type of
osteomyelitis that is caused by less virulent organisms.

Micro-organisms implicated in osteomyelitis include:

o Staphylococcus aureus (commonest)
o Salmonella typhi (common)
o non-Salmonella typhi spp (common)
o E. coli

21
 o Psuedomonas aeruginosa
o Enterobacter spp
o Hemophilus influenza type B
o Klebsiella spp
o Proteus spp

Bacteraemia caused due to the gram-negative microbes is believed to result from sickling within
the mesenteric vessels and subsequent gastrointestinal infarction and translocation of the GI
microorganisms into the bloodstream.

10.1 Clinical features

Acute Osteomyelitis:
• Fever or chills
• Irritability or lethargy in young children
• Pain in the area of the infection
• Swelling
• Warmth and redness over the area of the infection
• Loss of movement
• Sometimes no signs and symptoms or
• Have signs and symptoms that are difficult to distinguish from other problems such as
VOC.

Sub-acute osteomyelitis:
• Uncommon infection with bone pain
• Radiographic changes without systemic symptoms
• It is usually caused by indolent bacteria
• Characterised by a Brodie's abscess on imaging.

Post-acute osteomyelitis:
• Same as acute stage with increased bone pain
• Possible pyomyositis (abscess).

Chronic osteomyelitis:
• Pus discharge from sinus
• Pathological fractures presenting as acute pain
• Deformity or
• Inability to bear weight on the affected limb.

10.2 Differential diagnosis

• VOC (Bone infarctions)
• septic arthritis

22
• Local skin infection/ Pyomyositis (abscess)
• Tumour

10.3 Investigations
● Gold standard tools for the diagnosis is bone biopsy test with histopathological
examination and tissue culture, (both aerobic and anaerobic bacteria culture)
● FBC,
● Blood cultures, pus swab and culture
● CRP/ESR
● X- ray- Changes in acute osteomyelitis do not appear until about 10 days after the onset
of symptoms which coincides with the post-acute stage.
● Ultrasound/MRI in acute episodes are difficult to assess.
● Joint aspiration for culture of septic arthritis (never aspirate an affected joint without
prior consultation with a consultant).

10.4 Management
Acute osteomyelitis should be managed medically with antibiotics and no surgical
intervention is required.
● Cloxacillin for S. aureus osteomyelitis (commonest)
● If Gram stain shows gram-negative bacilli - add a third-generation cephalosporin,
● Ciprofloxacin can also be used especially when we suspect Salmonella species.

Note!! The total duration for antibiotic

 Administration should be for at least 4 – 6 weeks which should include 1-2 weeks of
intravenous administration.
 Serial infection markers should be done to monitor antibiotic response. ESR is less
reliable in neonates and sickle cell patients.

Other supportive management includes:

• Hydration
• Adequate pain management
• Rest of limb

Orthopaedics consultation:
For post-acute and chronic osteomyelitis
• Bone drilling if acute (to relieve the exudate and hence pressure in the medullary cavity to
prevent bone death; sequestrum formation) and post-acute osteomyelitis (to reduce the
pressure from the accumulated pus within the medullary cavity of the bone).
• Splintage of affected limb with Plaster of Paris (POP) or traction for pathological fractures
prior to referral
• Co-Management of patient by medical and surgical teams is needed.

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11. PERIOPERATIVE MANAGEMENT OF CHILDREN WITH SCD
Children with SCD are predisposed to complication requiring surgical procedures, such as
cholecystectomy and splenectomy. Peri-operative complications are higher in patients with SCD
compared with the general population and may be sickle or non-sickle-related. Complications
may be reduced by meticulous peri-operative care and blood transfusion.

A retrospective review by Griffin and Buchanan (1993) showed that for the majority of minor
elective procedures (hernia repair, circumcision, and dental rehabilitation) in sickle cell patients,
pre-operative transfusions are unnecessary, as these patients usually have uncomplicated courses.
On the other hand, patients undergoing thoracotomy, laparotomy, or
tonsillectomy/adenoidectomy are at higher risk of developing post-operative complications (the
rate is 50%) and may benefit from pre-operative transfusion regimens. These procedures are
characterized by longer intra-operative duration and by compromised chest wall and pulmonary
mechanics.

If transfusion is undertaken, the choice includes simple or exchange (automated or manual)

transfusion. A simple transfusion may be of benefit when the patient’s haemoglobin is below
baseline. But by raising Hb without significantly lowering HbS, a simple transfusion may
dramatically increase blood viscosity and thereby increase the risk of sickle-related
complications. Red cell exchange transfusion allows dilution of HbS without increasing
haematocrit. Transfuse RBCs in children with SCD to bring the haemoglobin level to 10 g/dL.

● Pre-operative assessment and preparation

o Senior member of the anaesthetic pre- assessment team should review elective
case to assess arrangements for pre- operative transfusion, requirement for an ICU
bed, and pain management plan.
o FBC, urea, electrolytes, creatinine, Hb electrophoresis, antibody screen (if
possible) and group and cross match must be done before surgery.
o Measure baseline oxygen saturation.
o Patient should receive either a simple blood transfusion or exchange transfusion
to bring the haemoglobin level to 10 g/dL prior to undergoing surgical procedure
involving general anaesthesia.
o Echocardiogram should be considered for in children with symptoms suggestive
of pulmonary hypertension (SpO2 < 94%, reduced exercise capacity).
o For children < 16 years of age, the results of transcranial Doppler (TCD)
assessment should be available and documented from the previous 12 months. If
abnormal, there should be a multidisciplinary discussion as to how the child
should be managed.
o Starvation instruction should be documented clearly and reinforced with the
patient and their family.
o All patients should be given warmed DNS IV for a minimum of 12 hours at
maintenance flow rate during starvation for the operation.

● Perioperative management
o The operating room should be pre- warmed, with assurance that temperature can
be well monitored and properly maintained, because hypothermia can trigger
24
 sickling.
o The patient should be well oxygenated pre- operatively; induction and intubation
should be undertaken with little or no hypoxic insult.
o The temperature should be monitored regularly postoperatively. Note that a spike
in temperature may be an early sign of sickling.
o Monitor oxygen saturation and Arterial Blood Gases (ABG) closely.

● Post- operative management

o This begins in the operating room, with assurance that the patient does not
become hypothermic, hypoxic, or hypotensive during emergence from
anaesthesia. Before extubation, the patient should be well awake, ventilating and
oxygenating well.
o In the recovery room, assess the patient carefully before transferring the child to a
paediatric ward. Request a CXR, if there is any concern about respiratory
function.
o Patients should be monitored for O2 saturation (aim to keep O 2 sat >96%);
children 4 years or older should be on a pulmonary clearing program (incentive
spirometry). If atelectasis or oxygen desaturation develops, seriously consider
admission to the ICU with intensified efforts at pulmonary clearing, including re-
intubation if necessary.
o Maintain hydration to prevent vasoconstriction, hypoperfusion, and microvascular
occlusion, which ultimately lead to sickling. Avoid over-hydration, however,
because pulmonary interstitial oedema can lead to hypoxia and a sickling crisis.
o Warmed intravenous fluids should be continued until the patient is able to tolerate
an adequate intake of oral fluids. Fluid balance should be monitored.
o Provide appropriate analgesia so that the patient is co-operative with ambulation
and pulmonary clearing, but not so much that he/she is constantly narcotized and
asleep.
o Patients with SCD are more susceptible to infection than the general population,
including respiratory and postoperative wound infections. Infection in the peri-
operative period may precipitate sickle complications such as painful crisis or
ACS. Antibiotic prophylaxis should be administered as dictated by the surgical
procedure.
o If operative complications develop or the patient becomes toxic or septic, consider
early transfer to the ICU (in consultation with paediatric haematology).

12. MANAGEMENT OF HYPERHAEOMLYSIS IN SICKLE CELL DISEASE

Hyperhaemolysis is a rare life threatening complication in SCD with rapidly dropping
haemoglobin, raised lactate dehydrogenase, intravascular haemolysis and haemoglobinuria
leading to multi organ failure and death.

It is characterised by rapid haemolysis following a blood transfusion, and the post- transfusion
haemoglobin will often be lower than the pre- transfusion haemoglobin, implying the destruction
of recipient as well donor red blood cells (RBCs).

25
Blood transfusion is an important treatment in the management of patients with SCD. However,
about one third of transfused SCD patients develop antibodies to red antigens, becoming
alloimmunized, and around 10% develop the most serious consequence of this alloimmunization
which is a delayed haemolytic transfusion reaction (DHTR).

The rapid haemolysis and may be associated with fever and with pain. The direct antiglobulin
test (DAT) may be either negative or positive and new red cell allo-antibodies are not usually
identified but may be present. There may be a reticulocytopenia. Hyperhaemolysis can recur in
such patients following blood transfusions several months or years after the initial episode.

Erythropoietin, iron replacement, B12 and folate replacement is usually required and should be
considered.

Hyperhaemolysis can recur many years after the first episode and transfusion is generally
avoided if possible in all patients who have had an episode. However, should a blood transfusion
be clinically indicated in such a patient, this must be discussed and agreed with a haematology
consultant, and the patients should be retreated with IVIG prior to transfusion. Patients with
hyperhaemolysis should be treated with intravenous immunoglobulin (IVIG) and IV
Methylprednisolone.

Diagnosis
Hyperhaemolysis should be considered in any patient with SCD who presents with increasing
haemolysis after a blood transfusion, typically, 1-week post transfusion, but may occur sooner
than this if the patient is re-challenged with transfusion.

Clinical features: Increasing jaundice, dark urine (‘coca-cola’ coloured), anaemia. They may also
have a fever, back, leg or abdominal pain, hepatomegaly or hepatic discomfort.

Investigations
 FBC: Worsening anaemia – Hb may fall to below the pre-transfusion level.
 Reticulocytes: May be raised (in keeping with haemolysis) or decreased, due to
suppression of red cell production.
 Direct Antiglobulin Test (DAT): Usually negative but can be positive, blood bank
should send for an eluate if DAT is positive.
 Group and screen: New allo-antibodies may be found but are usually absent.
 Haemoglobin electrophoresis to measure Hb S% and Hb A%: This is useful to
quantify how much, if any, Hb A (transfused blood) remains.
 Other markers of haemolysis:
o Raised Bilirubin
o Raised LDH
o Hyperferritinaemia may also be seen as a marker of macrophage activation

Treatment
 All SCD patients with suspected hyperhaemolysis must be discussed with a Haematology
Consultant.

26
  Supportive management should continue with analgesia, hydration and oxygen therapy as
required.

o Prescribe folic acid 5mg.

o Consider treatment with erythropoietin and providing IV iron replacement if not

iron replete (i.e. if ferritin <100 ng/ml).

o Consider B12 replacement.

 Blood transfusion may be necessary if clinically indicated (profound symptomatic

anaemia), but should only be given after discussion with the Haematology Consultant.

 Phenotyped blood should be given (CDE and Kell matched). Notify blood bank
immediately.

 Primary treatment is with IV Methylprednisolone and IVIG.

Dosage

 Intravenous immunoglobulin (IVIG)

Dose 1g/kg once daily for 2 days. Round the dose to nearest vial size (5 g, 10 g and 20 g vials
available).

 Methylprednisolone
Dose 10 mg/kg daily in 2 divided doses IV for 2 days. Maximum dose is 500 mg. Review dose
after 2 days.

 Erythropoietin
Dose 300 iu/kg once daily for 5 days. Then 300 iu/kg once daily on alternate days (i.e. 3 times
per week).

Hyperhaemolysis can be severe and there are documented cases that have had fatal outcomes. If
there is ongoing haemolysis despite actions above this must be discussed urgently with the
haematology consultant for SCD. There are case reports of successful outcomes using
eciluzimab and rituximab. These may be considered though not licenced yet.

Monitoring of treatment
 Haemoglobin: Target is return of haemoglobin to baseline.
 Stop erythropoietin if the haemoglobin returns to baseline, or if lack of response after full
treatment dose.

References
1. Guidelines for the Management of Sickle Cell Disease in Zambia. 2020.

27
2. Ware RE. How I use hydroxyurea to treat young patients with sickle cell anaemia? Blood.
2010;115(26):5300-11.
3. Canadian Haemoglobinopathy Association. Hydroxyurea. In: Consensus Statement on the
Care of Patients with Sickle Cell Disease in Canada. Version 2.0. Ottawa; 2015. pp.8-11.
4. Evidence- based management of sickle cell disease, expert panel report, 2014.
5. Paediatric Haematology/Oncology Ward officer’s handbook. Second edition. Texas
Children’s Cancer & Haematology Centre’s Global HOPE (Haematology- Oncology
Programs of Excellence) 2015.
6. Griffin TC, Buchanan GR. Elective surgery in children with sickle cell disease without
preoperative blood transfusion. Journal Paediatric Surgery. 1993;28(5):681–85.

7. Al Dallal SM (2017) Osteomyelitis: A manifestation of sickle cell anaemia. Clin Med Invest
2: DOI: 10.15761/CMI.1000132.

8. Win N, New H, Lee E, De La Fuente J. Hyperhaemolysis syndrome in sickle cell disease:

case report (recurrent episode) and literature review. (2008) Transfusion. 48; 1231-1238.

IMMUNE THROMBOCYTOPENIA

Definition:
● Platelet count < 100, 000 x 109/L, usually < 20 x 109/L.
● Self- limiting disease with shortened platelet survival and increased megakaryocytes.
Resolves in 80% of patients within 6 weeks to 6 months.
● Good prognosis.
● Acute 0- 3 months
● Persistent 3- 12 months
● Chronic > 12 months.
Mechanism:
● Shortened platelet survival due to platelet autoantibody production.
Diagnosis:
● Acute onset bruising, purpura and petechiae.
● History/evidence of mucocutaneous bleeding. petechiae, and bruising but otherwise
well appearing.
● History of previous viral infection in the last 2- 3 months (often, but not always) or
recent live virus vaccination administration.
● Absence of Hepatosplenomegaly, Lymphadenopathy, and evidence of serious
cause/chronic underlying illness.
● If headache and/or neurological signs, urgent CT scan of the head.
● Bone Marrow aspiration unnecessary unless:
o Neutropenia
o Hepatosplenomegaly
o Lymphadenopathy
o Pain limb/abdomen/back
o Limp.

28
 ● Isolated thrombocytopenia.
o Typically, < 20, 000/mm3.
o Smear results consistent with ITP
▪ Platelet size normal or large in size.
▪ Occasional giant platelets seen.
▪ Normal WBC and RBC morphology
▪ Microcytic, hypochromic red cells due to underlying iron deficiency is
common.
▪ Occasional activated lymphocytes can also be seen.
o Absence of tumour lysis (normal potassium, phosphorus, uric acid, LDH)
● ITP is a diagnosis of exclusion so a thorough history and physical examination and
work up needs to be taken. You must rule out leukaemia. If the following features are
present, then you need to think about a diagnosis other than ITP.
o Family history of low platelets
o Medication exposure including antibiotics, anticonvulsants, heparin, anti-
arrhythmia medication, sulfa drugs, aspirin.
o Haemarthroses or significant bleeding
o Evidence of active infection or fever.
o Arthralgia
o Weight loss, bone pain
o hepatomegaly, splenomegaly, lymphadenopathy.
o Dysmorphic features, skeletal abnormalities, growth delay, failure to thrive.
o Abdominal pain, bloody diarrhoea, renal failure, haemolytic anaemia in
additional to thrombocytopenia then think HUS/TTP.
o HIV risk- exposure of HV + status (although ITP is common with HIV).

Immediate Treatment
● None regardless of platelet count, unless life- threatening owing to significant
bleeding. Monitor platelet counts and educate the family about potential bleeding
symptoms.
● If significant bleeding (e.g. uncontrolled epistaxis, GI haemorrhage, intracranial
bleeding), give platelets along with immunoglobulin (IVIG) at 0.8- 1 g/kg by IV
infusion for 2 days.
● If moderate bleeding, prolonged mucosal bleeds, give prednisolone 2 mg/kg/day
(Maximum 120 mg daily) for 5-7 days only. There is no benefit with longer duration
of corticosteroids.
● Consider Tranexamic acid for mucosal bleeds.
● Avoid NSAIDs e.g. ibuprofen.
● Reassure parents. About 80% resolve in 6 months. Avoid contact sports.
● Continue monitoring FBC and PBS monthly until diagnosis is clear or recovery.

Chronic ITP
● Avoid NSAIDs
● Avoid contact sports

29
 ● Investigate for autoimmune diseases (ANA antinuclear antibody; APLA
antiphospholipid antibodies; ACA, anticardiolipin antibody; and LAC, lupus
anticoagulant) and immune deficiency (HIV, IgG, IgA, IgM).
● Treat only:
o Profound thrombocytopenia (<10 x 109/L) with repeated mucosal bleeding.
o Older girls with menorrhagia.
o Diminished health related quality of life
o Trauma
o Acute neurological signs
o If treatment indicated, give dexamethasone 0.6 mg/kg/day (maximum 40 mg).
o If unresponsive, discuss with paediatric haematologist about treatment with
thrombopoietin receptor agonist (eltrombopag) or rituximab.
o Splenectomy reserved for those with persistent/ significant bleeding non-
responsive or intolerant of other therapies.

References
1. American Society of Haematology 2019 guidelines for immune thrombocytopenia.
https://ashpublications.org/bloodadvances/article/3/23/3829/429213/American-Society-
of-Hematology-2019-guidelines-for

INFANTILE HAEMANGIOMA
Infantile haemangiomas (IH) are the most common vascular tumours, affecting around 4% of
infants. IH typically appear in the first few weeks of life and grow rapidly for the first few
months. Thereafter, slow proliferation can continue for up to 6- 12 months. Majority do not
require treatment due to their spontaneous involution. However, about 15% of IH result in
complications such as obstruction, ulceration, or disfigurement, and then require therapeutic
intervention.

Propranolol has become the first- line therapeutic agent in the management of complex IH.
Studies have shown that propranolol is a safe and effective treatment for IH in most patients.

Indications for initiating treatment with oral Propranolol

1. Vision compromise
2. Airway IH with actual or potential airway compromise.
3. Nasal IH with actual or potential obstruction
4. Lip IH causing actual or potential functional impairment and/or disfigurement.
5. Involvement of the auditory canal causing recurrent infection
6. Ulcerated IH, especially where topical treatment would not be appropriate or has not been
effective.
7. Risk of permanent disfigurement
8. Spinal cord cord compression by IH
9. Liver IH in conjunction with cutaneous IH in selected cases in collaboration with other
specialists.
30
Absolute Contraindications
1. Recent or ongoing hypoglycaemic episodes.
2. Second and third degree heart block
3. Hypersensitivity to propranolol hydrochloride.

Relative Contraindication
1. Frequent wheezing
2. Blood pressure outside normal range for age. Treatment in conjunction with paediatrician
is advised.
3. Heart rate outside normal range for age. Treatment in conjunction with paediatrician is
advised.

Baseline observations and investigations

● FBC
● Blood glucose
● Urea and electrolytes.
● Thyroid Function Tests (TFTs)
● Liver Function Tests (LFTs)
● ECG
● ECHO
● Liver ultrasound should be requested for infants with more than 5 cutaneous
haemangiomas to look for liver haemangiomas.
● MRI scan

Starting dose: A preparation of 1 mg/ml solution is preferable.

Week 1: Propranolol 1 mg/kg day in 3 divided doses
Week 2: Propranolol 2 mg/kg/day in 3 divided doses
Dose escalation: If response is unsatisfactory after 4 weeks (and no adverse effects have
occurred) the dose may be increased to:
Propranolol 3 mg/kg/day in 3 divided doses.

Follow- up:
Should be arranged 4 weeks after treatment commences.

Note: Medication should be given with or shortly after food. If an inter- current illness causes
significant vomiting, propranolol should be temporarily withheld to reduce the likelihood of
hypoglycaemia.

Potential side effects:

● Bradycardia
● Hypoglycaemia
● Heart failure
● Hypotension
● Cardiac conduction disorders
● Bronchospasms

31
 ● Peripheral vasoconstriction
● Weakness and fatigue
● Sleep disturbances

Administration:
Use of the medication should be explained to the parents and information leaflet provided.
Advice on potential side effects should be explained to parents prior to starting therapy.

Stopping Propranolol
Propranolol should be temporarily discontinued in the setting of significant reduced oral intake
or of the patient has wheezing that requires treatment.

Treatment of IH should extend beyond the proliferative period of IH to avoid rebound growth
and the decision when to stop treatment will have to be guided by clinical features. There is no
uniform cut off age that determines the risk of rebound growth, although a European study
suggested that children aged 17 months or older had a significantly lower risk of rebound growth
compared to younger age groups.

References
1. Solman, L et al (2017) Propranolol in the treatment of infantile haemangiomas: The British
Society for Paediatric Dermatology consensus guidelines.
2. Laeaute- Labreze C, et al (2015) A randomized, controlled trial of oral propranolol in
infantile haemangioma. New England Journal of Medicine; 372:735- 46.
3. Wedgeworth E et al (2016) Propranolol in the treatment of infantile haemangioma: lessons
from the European Propranolol in the Treatment of Complicated Haemangiomas (OITCH)
Taskforce survey. The British Journal of Dermatology.

APPENDIX 1
Mild to Severe Pain, and Pain Scales

A child with mild pain:

● Rates his/her pain as 1–3 on a Verbal Report Scale (of 0–10).

● May not appear uncomfortable, but complains of pain.
● May or may not be crying, may have a neutral facial expression, and may be at rest or
shifting position in chair.

A child with moderate pain:

● Rates his/her pain as 4–6 on the Verbal Report Scale (0–10).

● May show facial grimacing, unhappiness, irritability, and a poor appetite.
● May (according to the family) have been unable to carry out normal daily activities, or
been uninterested in social interaction.

A child with severe pain:

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 ● Rates his/her pain as > 7 on the Verbal Report Scale (0–10).
● Show facial grimacing, unhappiness, irritability, and a poor appetite.
● Is generally crying, very uncomfortable to the point of agony.

The Verbal Pain Report Scale

The Verbal Report Scale is a self-reported tool used across units at the University Teaching
Hospitals (UTHs)- Children’s Hospital.

The person administering this tool says to the patient, “On a scale of 0 to 10, with 0 being ‘no
pain’ and 10 being ‘the worst pain ever’, how would you rate your pain?”

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