Author: Dr. M.A. Barry

Reviewed by: Dr. Sara Loetz, Professor Samuel Adegoke, Professor Stephen Allen

Date: 20.07.2025, Version 1.1

Next review: 1.2027

Definition:

• Sickle Cell Disease: A qualitative haemoglobinopathy characterized by the presence of haemoglobin S in combination with another abnormal haemoglobin., e.g., haemoglobin S, C, tha, O-Arab, D Punjab, etc. SCD includes:

• Homozygous SCD, also known as sickle cell anaemia, i.e., HbSS (Homozygosity for HbS)

• Heterozygous SCD such as HbSC, HbS-β-thalassaemia, HbSO-Arab, HbS-D Punjab, etc. Note that Sickle Cell Trait (HbAS) is not a sickle cell disease. Individuals with sickle cell trait are usually asymptomatic.

ASSESSMENT

Emergency Signs?

Important Points in History

Nonspecific symptoms:

• Fatigue, Headache, Dizziness, fever, pain

Specific symptoms:

• Dyspnea, Cough, Abdominal distension, swelling of the hands and feet, leg ulcers

History to identify trigger factors if in vaso-occlusive crisis (VOC): Acronym – ACIDOSES

• Acidosis

• Cold - exposure

• Infections – commonest cause. Most commonly Malaria

• (Progressive splenic infarction leading to functional asplenia), (fever, cough, or breathlessness, bone or joint pain, myalgia, dysuria)

• Dehydration (reduced fluid intake, vomiting, diarrhea)

• Oxygen lacks (hypoxia), also due to smoky rooms

• Stress, including anesthesia and surgery, school work

• Elevated temperature (fever)

• Sport (Strenuous exercise)

Past Medical Hx:

• Previous VOC,

• Painful swelling or the fingers or toes during infancy.

• Diagnosis of SCD made? Where and how? Follow-up at clinic? On which medication

• Blood transfusion and if recurrent

Immunization Hx: Pentavalent (including HiB) and Pneumococcal conjugate vaccine as in national immunization schedule. Meningococcal?

Family & Social Hx:

• SCD in the family (autosomal recessive disease), Genotype of parents and siblings

Important Points on Examination

• General:

• Appearance and sickle cell habitus/peripheral stigmata

• Frontal and parietal bossing, recurrent jaundice, long and thin limbs, protuberant abdomen, gnathopathy (Hyperplasia of Maxilla), spindle shaped painful digits

SOP Sickle cell disease, EFSTH

• Appears to be in pain

• Fever (infection), dehydration, signs of shock

• VOC: painful distress; respiratory distress & cyanosis -with acute chest syndrome

• Hemolytic crisis: Pallor, jaundice

• RS: Tachypnoea, low SpO2 in ACS – Severe Hypoxia is a valuable predictor of severity and outcome

• CVS: Tachycardia, Bounding pulse (aneamic heart failure due to haemolytic crises), slow thready pulse & low BP (acute sequestration crises)

• DS: Tenderness in VOC; splenomegaly (compare with medical record to see if sudden enlargement in acute splenic sequestration (ASS)), tender hepatomegaly in heart failure

• MSK: examine limbs for tenderness, differential warmth, and swelling, deformities. Bone pain (especially long bones in VOC)

• CNS: Signs of CVA: Hemiplegia, gait disorders, ...

• Other relevant findings based on complications or comorbidity

• Vital signs (incl blood pressure)

• Relevant Investigations general

• Screening: [Sickling test (low sensitivity & specificity)], better Hb electrophoresis, peripheral blood smear

• Confirmatory: High-performance liquid chromatography (HPLC):

• Quantitative accuracy: Precisely measures percentages of all Hb types (HbA, HbS, HbA2, etc), crucial for differentiating trait from disease.

• High resolution

• Superior to the above tests but not currently available in The Gambia.

• FBC – usually Leukocytosis (even if plus fever does not always indicate infection as VOC are due to ischaemia), anaemia, elevated platelets

• Grouping and crossmatch if pale

• Annual HIV, Hep B & C check for those on chronic blood transfusion.

• Other additional tests guided by complaints: e.g., Peripheral blood smear, BF for Malaria, Blood culture (sepsis), RFTs and LFTs if jaundiced,

urinalysis and mcs. X-ray of affected bone to rule out osteomyelitis, LP for

CSF analysis …

MONITORING

• Vital signs depending on condition. Commonly 4-6 hrly, in ACS 2 hrly

(increasing respiratory rate and Hypoxia). In acute sequestration 1 hrly

• Closely observe level of jaundice and pallor

• Others depending on specific condition

MANAGEMENT

• Genera l

• Anaemia

• Usually, onset at 6th month of life. However, may occur in early infants

(less than 6 months). Symptoms Fatigue, Dyspnoea, Pallor

• Blood transfusion should be reserved for the following circumstances:

• Urgently for sudden, severe anaemia due to ASS, parvovirus B19

infection, or hyperhaemolysis crises.

• Transfusion is indicated in the following situations:

• Stroke, ACS, Multiorgan failure, recurrent or severe priapism that

does not resolve after adequate hydration and analgesia, severe

anaemia (Hb <4 g/dl), symptomatic anaemia, perioperative.

• Warmth

• Oxygen if SpO2 below 90% if only respiratory symptoms, below 94% if other

SOP Sickle cell disease, EFSTH

emergency symptoms

• Analgesia:

• aim to control pain as fast as possible to prevent further sickling and

complications

• Use a standardized scale to assess pain. (0: No pain. 1-3: Mild pain, 4-6:

Moderate pain, 7-10: Severe pain). If score is > 4 (increasing the)

analgesia is required

• → See pain SOP

• Infections (functional asplenia, impaired immunity and defects in

opsonization)

• Especially from encapsulated organism

• Broad spectrum antibiotics

• Sepsis (usually S. pneumo): Ceftriaxone

• Meningitis (usually S. pneumo): Ceftriaxone x 2 weeks

• Acute Chest Syndrome: Ceftriaxone

• Salmonella osteomyelitis: Ceftriaxone (IV antibiotics for 2 weeks) then

consider change to oral antibiotics (Ciprofloxacin). Total duration of

antibiotics 4-6 weeks

• Always check for Malaria parasites

Complications/Specific conditions and their management

• Vaso-occlusive crisis (VOC): due to increased viscosity and sludging

associated with sickling that leads to obstruction of blood flow in the

microcirculation. This leads to restricted oxygen delivery to the tissues

• Specific hx:

• Pain: Severe skeletal pain, especially in the limb,s back, abdominal or

chest. Pain character: generalized or focal, but not finger point pain as

seen in osteomyelitis.

• Limb pain may be associated with inability to use or walk with affected

limb.

• Precipitating factors (see above, acronym ACIDOSIS)

• Management for all VOCs

• Oxygen: Aim for SpO2 > 94%

• Analgesia: control pain

• Hydration: IVF 1.5 x daily maintenance volume (unless ACS). NB

preferred fluid is 0.9%N/saline or R/Lactate.

• Investigate and treat underlying cause

• Specific forms of VOC:

• Bone crisis: involves the bones with the most marrow activity

• In 6 months to 2yrs metacarpal and metatarsal bones: Dactylitis:

Tender, warm & non-pitting swelling of the distal part of hand and feet

• long bones, ribs and sternum in older children. Multiple sites may be

involved, may mimic osteomyelitis with point tenderness

• DD. Septic arthritis, osteomyelitis

The following table would help to differentiate between SCD bone crisis

and Osteomyelitis.

SOP Sickle cell disease, EFSTH

Feature Bone Crisis (VOC) Osteomyelitis

Onset of Pain • Sudden • Gradual or subacute;

may follow VOC

Pain Characteristics

(may not be obtained in children)

• Deep, throbbing; often

in long bones or spine

• Localized, persistent;

may worsen over time

Fever • Low-grade or absent • Moderate to highgrade;

often persistent

Duration of symptoms • Short (1-3days) • Longer (5 days or

more); progressive

History of similar episodes • Often recurrent • Usually isolated or

new episode

Swelling & Erythema • Mild, diffuse; may be

symmetrical

• (e.g., dactylitis)

• Localized,

pronounced; often unilateral

Warmth over site • May be present • Typically present

WBC &/or CRP • Mild-moderate elevation • Markedly elevated

Blood Culture • negative • May be positive (esp.

for salmonella or S. aureus)

Ultrasound findings • No fluid collection;

periosteal elevation rare

• Subperiosteal fluid

collection >4 mm common

Response to Analgesia • Good response to

opioids

• Poor response; pain

persists despite analgesia

• Abdominal crisis

• DD acute abdomen

•

• Acute chest syndrome : (severe, life-threatening complication of

intrapulmonary sickling and lung infarction). Early recognition and

treatment is essential. 10% of cases will progress to acute respiratory

failure. Aetiology is multifactorial, but often involving infection (50%, often

atypical bacteria like Chlamydia or Mycoplasma). Or while hospitalized for

a VOC of the bones - infarction, fat embolization from the long bones,

hypoventilation (e.g., due to pain) and iatrogenic overhydration can cause

ACS.

• Risk factors: highest incidence 2-4 years, low Hb, high steady state

WBC, SS, VOC of spine, ribs, abdomen, post op atelectasis, asthma,

hypoventilation, opiate overdose, fluid overload, tabacco smoke

exposure

• History and examination:

• Chest pain. Tachypnoea, Dyspnoea, wheeze

• Hypoxia – level of hypoxemia is a useful predictor of severity and

outcome. Monitor closely (best continuously)

• Cough, but on auscultation usually clear chest

• Fever can be present

• Specific investigations: Chest x ray: new infiltrations? DD Pneumonia.

NOTE: often radiography behind clinical findings – might still be

normal even if already severe disease

• Specific management – Treat prompt and aggressively

• Correct dehydration, then remain on IV maintenance at

usual volume for age, NOT 1.5x maintenance [Fluid to use is

0.9% N/Saline or R/Lactate]

• Prompt, sufficient pain relief

• Encourage deep breathing: Spirometry (let the child blow up an

inflatable latex balloon multiple times a day) – to prevent and open

atelectasis

• Transfuse whole blood if SpO2 < 94% (on RA) or severe

respiratory distress and/or Hb < 9 g/dl. Aim for an Hb of 10-11 g/dl.

SOP Sickle cell disease, EFSTH

• Exchange transfusion if no improvement after initial transfusion

or SpO2 still not > 94% (on RA) or if severe respiratory distress or if

Hb is > 10 g/dl

• Antibiotics: Ceftriaxone and Macrolides (e.g. Azithromycin 10 mg

TDS 5/7)

• Salbutamol neb and steroids if acute bronchospasm

• Priapism - Urological emergency

• Hx and examination: prolonged and painful penile erection lasting > 4

hours

• Medical Management

• Conservative management (trial for 2 hours): Urinate often,

increase fluid intake, Analgesia, warm bath.

• Pharmacological management:

• Analgesia: NSAIDs for milder pain and opioids for moderate to severe pain.

(See SOP on pain management for dosages and medication or refer to BNF

for Children)

• Alpha-1 adrenergic agonists

• 1st line pharmacological management, often performed after or in

conjunction with corporal aspiration.

• Phenylephrine: 100-150 mcg diluted in N/Saline, injected directly into

the corpus cavernosum. Dose can be repeated every 5-15 minutes, up to a

maximum dose of 1 mg within 1 hour.

• Close monitoring of BP and heart rate as it can cause systemic

hypertension and reflex bradycardia.

• Other medications to consider:

• Hydroxyurea: for a long-term management of recurrent priapism

• Oral pseudoephedrine: an Alpha-adrenergic agonist, can be used on

demand or short-term prophylactic agents to abort an impending episode.

However, a Cochrane review noted uncertain evidence for their routine

use in preventing recurrent ischemic priapism in SCD.

• Exchange transfusion

• Consult pediatric surgery/urology if no response to medical

management

• Stroke (cerebrovascular accidents) – due to chronic intracranial

arteriolar stenosis or obstruction in the internal carotid and proximal

middle cerebral or anterior cerebral arteries plus acute sickling →

hypoxia to part of the brain. CVA affects 6-17 % of children with SCD.

85% infarction, 5% hemorrhagic, 10% mixed. Commonly at 5-10 years

• Hx and Examination:

• sudden neurological deficit e.g., difficulties speaking, seizures,

motor and sensory deficits (hemiparesis or hemiplegia with

gait dysfunction), reduced level of consciousness

• sometimes headaches

• Risk factors: elevated WCC, hx of dactylitis, low Hb (< 7g/dl),

systolic hypertension, family hx of stroke associated with SCD,

frequent ACS, bacterial meningitis

• More common in evolving VOC or ACS, priapism or febrile illness.

• Investigation: Non contrast CT (will be positive after 6 hrs. of

onset of symptoms) or better MRI (better detail, more sensitive,

detects strokes early)

• Management:

• Maintain the airway if at risk (position, guedel airway)

• Oxygen to keep SpO2 > 94%

• IV 0.9% N/saline maintenance volume if there is no hypovolemia. If

there is, correct the hypovolemia with 10-20ml/kg 0.9%N/Saline or

SOP Sickle cell disease, EFSTH

R/Lactate over 30-60 minutes, then continue with the normal

maintenance.

• Treat convulsions

• Exchange blood transfusion, keep Hb above 10 g/dl [the gold

standard of Sickle cell stroke management]

• Physiotherapy when stable and planning for discharge and/ or on

follow-up visits.

• Full recovery within weeks in 2/3 of children. Risk of recurrence

within 3 years.

• Hyperh a emolytic crisis: RBCs are broken down at a more rapid rate

than when in a steady state of the disease. This usually due to malaria

or a bacterial infection.

• Specific history

• Deepening yellowness of eyes

• Dark brown colored urine

• Paleness of palms and soles or worsening pallor

• Body weakness

• Precipitating factors: infections or red cell enzymopathy like G6DH

deficiency

• Reticulocytosis, increased bilirubin, increased lactate

dehydrogenase

• Management

• Urgent PCV check, grouping and cross match

• Correct anemia by blood transfusion with packed cells 15ml/kg

• I.V Furosemide 1mg/kg if in cardiac insufficiency due to the

anemia

• Give oxygen

• Hydration as in VOC

• Investigate and treat underlying precipitant

• Monitor urine color

• Aplastic crisis: Bone marrow shutdown, mostly due to parvovirus B19

(rare!). VOC and sequestration can be associated

• history and examination

• Profound anemic features

• Reticulocytes low

• Management (supportive)

• Transfuse packed cells 10 ml/kg

• Resolves after ca. 10 days

• Acute splenic sequestration (ASS) crisis (most common between 6

and 24 month): Due to pooling of blood in the spleen. Liver might be

involved as well. Hb decrease at least by 2g/dL from the steady-state

Hb concentration – leading to anemia and hypovolemia. Might be the

first presentation of a child with SCD. Can be present at the same time

as ACS.

• History and examination:

• Massive splenomegaly (Abdominal distension) or sudden increase in

spleen size +/- hepatomegaly.

• Depending on the number of red cells trapped in the spleen:

symptoms of severe anaemia with anaemic heart failure to shock

with hypovolaemia and hypotension

SOP Sickle cell disease, EFSTH

• Sudden weakness

• Fainting spells or dizziness

• Left-sided abominal pain

• Sudden Hb drop: (increasing) pallor - anaemia can be life

threatening

• Reticulocytosis, mild thrombocytopenia, fall of WCC from

baseline level

• Management

• Treat shock if present with N/S/RL 20ml/kg while awaiting blood

• Oxygen

• Transfuse blood ((5-)10ml/kg of packed cell in aliquots) – do not

transfuse more as sequestered RBC may reenter the circulation

and cause fluid overload.

• Exchange blood transfusion may be indicated if there is Acute

Chest Syndrome or re-entry of pooled blood into the circulation

(Reverse sequestration).

• Monitor urine output and vital signs

• Monitor spleen size - Spleen decreasing in size makes the

diagnosis more likely

• Long term management:

• Splenectomy (to avoid recurrence), usually from the age of 2

years

• Recurrent cholecystitis/cholecystitis (> 10 years)

• jaundice and enlarged liver

• right upper quadrant and epigastric pain

• Investigations. Abdominal ultrasound and surgical review

• Management: Ceftriaxone and Metronidazole, cholecystectomy

• Chronic lung/ cardiac problems (e.g. pulmonal hypertension)

Ongoing management (in between crises):

• Avoid precipitants of crises

• Folic Acid (5 mg OD) once a week

• Weekly Fansidar:

• 5-10 kg: . tablet once weekly, 11-20 kg: . tablet once

weekly, 21-30 kg: . tablet once weekly, 31-40 kg: 1 tablet

once weekly, > 45 kg1.5 tablets once weekly or daily

proguanil for malaria prophylaxis

• Penicillin PEN V prophylaxis

• < 1 years: 62.5 mg BD, < 5 years: 125 mg BD, >5 years 250 mg

BD

• Hydroxyurea – see flowchart below

• Fe - Chelation therapy with desferoxamine from repeated blood

transfusions if available

• Paracetamol 15 mg/kg QDS in case of painful crisis to start at home

• Vaccinations including Streptococcus pneumoniae, and HiB vaccines (part

of routine vaccination in the Gambia), Neisseria meningitides.

• Support optimal nutrition (at risk for growth retardation)

• Educate to seek medical attention if severe pallor, severe pain,

tachypnea, high fever, vomiting/diarrhea

• Prompt Rx of malaria and other infections

SOP Sickle cell disease, EFSTH

• Monitor for renal complications (Proteinuria)

• Transcranial doppler (if trained staff available). Normal velocity is < 170

cm/sec. If > 200 cm/sec indicates high risk of stroke

• Bone marrow transplant (Not available yet in the Gambia)

EXCHANGE TRANSFUSION

• Indication: ACS, Stroke

• cannulate two large veins

• withdraw blood from 1 cannula (Use a BP cuff and inflate it to

midline BP between systolic and diastolic to allow best outflow)

• infuse blood into the other vein (can be done simultaneously)

• 10 ml out, 8 ml in. Give 1 ml Calcium gluconate for every 100 ml

Whole blood

• One partial exchange is 20 ml/kg whole blood (max 1 pint). May

be repeated after 6-12 hours. This procedure may reduce HbS by

up to 50% and reverses the sickling, delivers more red cells

which leads to better oxygenation of tissue, including the lungs

FLOWCHART

Simplified protocol for Hydroxyurea therapy in children with sickle cell

disease

→ Myelosuppressive agent – reduced frequency of VOC/acute chest syndrome,

raises HbF level and Hb (and therefore need for transfusions and hospitalization).

1. Identify patients

All HbSS, SbetaThal, SC, S-O Arab, S-D Punjab); age > 9 months). In LMICs: severe

disease (painful crisis > 3/year, anaemia (eg transfused > 2x /year) or ACS,

priapism, splenic sequestation persistent anaemia, primary or secondary stroke

prevention, progressive organ damage due to SCD etc)

2. Counseling and consent taking

Indications, benefits, costs, regular tests, potential side effects: Bone marrow

suppression: neutropenia - risk of infections, bleeding, worsening anemia (rare),

elevated liver enzymes, nausea, headaches, skin changes

3. Baseline investigations

Confirm diagnosis: Hb electrophoresis

SOP Sickle cell disease, EFSTH

HBV/HCV Serology, HIV Test, FBC, RFT, LFT, HbF, pregnancy test for adolescent

females

4. Initiation of Hydroxyurea

15 mg/kg/d. Low dose of 10 mg/kg/d can be used

5. Laboratory monitoring

FBC: 2 weeks after initiation, then monthly thereafter

LFT/RFT: 3 monthly on 2 occasions after initiation, then 6 monthly

HbF: 6 monthly to yearly

6. Dose escalation

5 mg/kg/day every 2-3 months. Monitor lab and clinical side effects

A clinical response might take 3-6 months

7. Establish maximum tolerated dose (MTD)

Dose beyond which patient start showing lab or clinical side effects of the drug.

Neutrophils < 1500/μl, WCC < 4000/μl, platelet counts < 8000/μl, fall in Hb > 20%

of previous value, renal (creatinine) or LFT (ALT) values double of baseline

Exact dose and schedule will need to be determined by capsule size (usually

500mg) and availability of liquid preparation. In smaller children, consider alternate

day dosing and/or giving half capsule/day (but do not exceed a dose of 35mg/kg on

any single day)

→ If no side effects: Maximum dose 35 mg/kg/d

→ If side effects: withhold temporarily, Monitor clinically. Repeat lab 2 weekly until

recovery. Restart at the same dose or at 5 mg/kg/day less than the toxic dose on

the last MTD

CHRONIC BLOOD TRANSFUSION

Defined as regular, long-term administration of blood cells to a patient, typically

every 3-5 weeks, with the goal of preventing or managing complications of certain

hematologic or genetic conditions (SCD in this context).

• Indications

• Stroke prevention (primary and secondary stroke)

• Recurrent Acute Chest Syndrome

• Recurrent VOCs and pains not controlled by hydroxyurea

• Severe Anemia and organ damage

• Pregnancy in SCD (for adolescents)

• Unavailability of hydroxyurea

• Due to factors such as limited availability, high cost, risk of transfusion

reactions and alloimmunization, and low cultural acceptability,

hydroxyurea (HU) is increasingly used as a viable alternative.

Importantly, HU has been shown to be non-inferior to CBT in stroke

prevention and may outperform CBT in preventing or managing certain

complications in some studies.

• Observe the basic steps regarding blood transfusion (i.e annual screening for

HIV, HBV & HCV) and base line iron studies (ferritin and transferrin studies)

when available and affordable.

• Consider Iron chelation therapy

REFERENCES

• Ibekwe, Maryann, Practical Approach to Paediatric Emergencies in the

Tropics, 2015

• World Health Organisation: Pocket book of primary health care for children

and adolescents: guidelines for health promotion, disease prevention and

management from the newborn period to adolescence. 2022

• World Health Organisation: Pocket book of hospital care for children. 2nd

edition. 2013

• Uptodate

• Paediatric association of Nigeria: Guideline Acute chest syndrome 2024

• American Society of Hematology Clinical Practice Guidelines