Sickle cell disease

– Homozygous sickle cell disease (SCD) is a life-threatening genetic disorder of haemoglobin (Hb). The abnormal Hb (HbS) results in the distortion of red blood cells into a sickle shape leading to increased destruction (haemolysis), an increase in blood viscosity and obstruction of capillaries (vaso-occlusion).
– SCD is common in sub-Saharan Africa (1 to 3% of births), on the American continent, in India and in the Mediterranean basin.

Clinical features

– Symptoms generally begin after 6 months of age.
– Major signs: recurrent painful crises, chronic anaemia, splenomegaly and frequently, growth retardation and malnutrition in children.
– Serious acute life threatening complications such as stroke, overwhelming infections and acute chest syndrome.
– In populations in whom the disease is frequent, diagnosis is suggested by a family history of similar clinical signs.

Major acute manifestations

Painful vaso-occlusive crises (VOC)

– Children under 2 years present with the hand-foot syndrome or dactylitis (acute pain and swelling in the hands or feet).
– Children older than 2 years and adults present with acute pain affecting the back, chest, abdomen (can resemble an acute abdomen) and extremities.
– Young children may have non-specific signs of a VOC: refusal to walk, irritability, lack of appetite, crying, whimpering or moaning when touched, etc.
– Look for an associated infection that might have precipitated the VOC.
– In case of bony pain in a single location, unresponsive to analgesics (or a persistent limp in a child) associated with fever and erythema or swelling, consider an osteomyelitis.


Look for infection: in particular pneumonia, cellulitis, meningitis, osteomyelitis and sepsis (patients are particularly susceptible to infections especially due to pneumococcus, meningococcus and Haemophilus influenzae); malaria.

Acute severe anaemia

– The chronic anaemia is often complicated by acute severe anaemia with gradually appearing fatigue, pallor of the conjunctivae and palms, shortness of breath, tachycardia, syncope or heart failure.
– The acute anaemia can be due to:
• Acute severe haemolysis often secondary to malaria: fever, haemoglobinuria (dark urine) and yellow conjunctivae.
• Splenic sequestration (trapping of blood cells in the spleen), mostly in children 1 to 4 years: sudden enlargement of the spleen, severe left upper quadrant pain, thrombocytopenia. Can lead to shock.
• Aplastic crisis (transient suspension of red blood cell production by the bone marrow): impalpable spleen and absence of reticulocytes.


– Most often ischaemic (due to vaso-occlusion in cerebral vessels) but a stroke can also be haemorrhagic.
– Sudden loss of motor function or aphasia, in children and in adults.
– Signs can resemble meningitis and cerebral malaria: headache, photophobia, vomiting, stiff neck, alteration of consciousness and neurologic signs or rarely seizures.

Acute chest syndrome (ACS)

– Chest pain, tachypnoea, respiratory distress, hypoxia; fever (more frequent in children); pulmonary infiltrate on chest x-ray. Often proceeded by a VOC.
– Complications: multiorgan failure (lung, liver, kidney).


Painful prolonged erection in the absence of sexual stimulation, also occurring in young boys. Risk of necrosis and irreversible erectile dysfunction.

Laboratory and other investigations


– Hb electrophoresis confirms the diagnosis but is often unavailable.
– If not available, a positive Emmel test (or sickling test) in the presence of clinical signs of sickle cell disease supports the diagnosis.

Other examinations




• At the time of diagnosis and annually (frequently 7 to 9 g/dl).
• In case of VOC, fever, acute anaemia (≤ 5 g/dl or drop in Hb ≥ 2 g/dl below the patient’s baseline), stroke, ACS.
• For monitoring of transfused patients.


• At the time of diagnosis and annually.
In case of acute anaemia (thrombocytopenia - platelet count 100 000/mm3 if splenic sequestration).

Urine dipstick

• In case of fever: look for a urinary tract infection.
• In case of acute severe anaemia: look for haemoglobinuria.

Malaria test

In case of VOC, fever, acute anaemia or stroke.

Lumbar puncture

In case of fever with meningeal signs or unexplained coma.

(if available)

• Complete blood count and reticulocyte count.
• Blood culture in case of fever.
• X-ray if suspicion of pneumonia, osteomyelitis, ACS.

Management of major acute manifestations

Painful vaso-occlusive crisis (VOC)

– Moderate pain (at home):
• Generous oral hydration (water, soup, juice, coconut water): minimum 100 ml/kg daily in children and 50 ml/kg daily in adults (2.5 to 3 litres daily);
• Warm compresses (application of cold is contra-indicated);
• Level 1 (paracetamol and ibuprofen) and level 2 (tramadol) analgesics;
• If pain is not controlled at home within 24 hours, seek medical attention.

– Severe pain or pain not controlled at home (in hospital):
• PO hydration (as above); if the patient is unable to drink sufficiently, IV hydration (Appendix 1); in the event of dehydration, treat according to the degree of dehydration (see Dehydration, Chapter 1);
• Level 3 analgesics (morphine);
• Do not give routine antibiotics in the absence of fever; do not transfuse for VOC.

For the treatment of pain according to intensity, see Pain (Chapter 1).

Fever and infection

– Admit to hospital:
• All children less than 2 years;
• Children with fever ≥ 38.5 °C and adults with fever ≥ 39.5 °C; patients who are critically ill appearing1 or have acute anaemia.

– PO or IV hydration (Appendix 1).
– Treat malaria if present.
– Treat bacterial infections according to cause.
– Treat all patients with respiratory symptoms for pneumonia and ACS.
– In case of osteomyelitis:
ceftriaxone slow IV2 injection (3 minutes) or IV infusion (30 minutes)
Children < 40 kg: 50 mg/kg every 12 hours
Children ≥ 40 kg and adults: 2 g every 12 hours
cloxacillin IV infusion (60 minutes)3
Children < 40 kg: 50 mg/kg every 6 hours 
Children ≥ 40 kg and adults: 3 g every 6 hours 
Administer IV therapy for at least 14 days. Then if the patient has improved, change to the oral route for an additional 14 days of treatment with a combination of:
ciprofloxacin PO
Children < 35 kg: 15 mg/kg 2 times daily
Children ≥ 35 kg and adults: 500 mg 2 times daily
amoxicillin/clavulanic acid PO (see below) 

– If the source of infection is unknown:
ceftriaxone IM or slow IV2  injection (3 minutes) or IV infusion (30 minutes)
Children < 20 kg: 50 mg/kg once daily (max. 2 g/day)
Children ≥ 20 kg and adults: 1 to 2 g once daily

After 48 hours re-evaluate the patient:
• If the patient is improving (afebrile, can drink), change to:
amoxicillin/clavulanic acid (co-amoxiclav) PO for 7 to 10 days. Use formulations in a ratio of 8:1 or 7:1 exclusively. The dose is expressed in amoxicillin:
Children < 40 kg: 50 mg/kg 2 times daily 
Children ≥ 40 kg and adults:
Ratio 8:1: 3000 mg daily (2 tab of 500/62.5 mg 3 times daily)
Ratio 7:1: 2625 mg daily (1 tab of 875/125 mg 3 times daily)
Patients over 2 years without acute anaemia can continue treatment as outpatients.
Patients under 2 years or with acute anaemia or who cannot be monitored and treated at home by their family should complete PO antibiotherapy in hospital.
• If the patient is not improving, continue ceftriaxone until the patient is afebrile, then, change to PO treatment. Monitor for acute anaemia.

Acute severe haemolysis

– Admit to hospital.
– Treat malaria if present.
– Transfuse packed red blood cells4 5 if Hb < 5 g/dl or drop of 2 g/dl below the patient’s baseline. Target a Hb level of 9 g/dl.
• Start with 10 to 15 ml/kg in 3 to 4 hours. For information, 10 ml/kg of packed red blood cells usually raise the Hb by 2.5 g/dl.
• Repeat the Hb. If a second transfusion is needed, check for signs of fluid overload before starting the transfusion.
• Measure Hb and perform urine dipstick in the following days. Further transfusions may be necessary if haemolysis is ongoing.

Aplastic crisis

– Admit to hospital.
– Treat an associated bacterial infection if present.
– Transfuse as for haemolysis. Repeat the Hb every other day. An increasing reticulocyte count and a gradual increase of the Hb indicate improvement. Follow patient until they have reached their baseline Hb.

Splenic sequestration

– Admit to hospital.
– Treat hypovolaemic shock if present.
– Monitor the size of the spleen.
– Transfuse if Hb < 5 g/dl, target a Hb level of 7 to 8 g/dl maximum.
– Administer ceftriaxone as above.
– After clinical improvement, monitor for relapse (follow the size of the spleen).
Note: splenectomy is contra-indicated (high operative mortality).


– Admit to hospital.
– The treatment of choice for ischaemic stroke is an exchange transfusion to lower the concentration of HbS. Transfer the patient to a specialized facility for further management (including prophylactic therapy to prevent recurrences with transfusion program, hydroxyurea).
– If the patient is awaiting transfer or if transfer is not possible:
• Oxygen continuously, at least 5 litres/minute or to maintain the SpO2 between 94 and 98%.
• Treat seizures if present.
• Transfuse if the Hb ≤ 9 g/dl. Target Hb of 10 g/dl.
• After the transfusion provide IV hydration (Appendix 1).

Acute chest syndrome

– Admit to hospital.
– Measure SpO2 and administer oxygen as in stroke.
– PO hydration as for a VOC; if the patient is unable to drink sufficiently, IV hydration (Appendix 1) while monitoring for fluid overload; in the event of fluid overload, administer one dose of furosemide IV (see Dehydration, Chapter 1).
– Antibiotics:
ceftriaxone slow IV2 injection (3 minutes) or IV infusion (30 minutes) for 7 to 10 days
Children < 20 kg: 50 mg/kg once daily (max. 2 g daily)
Children ≥ 20 kg and adults: 1 to 2 g once daily
azithromycin PO for 5 days
Children: 10 mg/kg once daily (max. 500 mg daily)
Adults: 500 mg on D1 then 250 mg once daily from D2 to D5

– Transfuse if symptoms are unresponsive to antibiotics and Hb < 9 g/dl.
– If wheezing is present treat with:
salbutamol aerosol (100 micrograms/puff)
Children and adults: 2 to 4 puffs with a spacer every 10 to 30 minutes as needed
– Encourage deep breathing (incentive spirometry hourly).
– Treat pain (see Pain, Chapter 1).


– PO hydration as for a VOC; IV hydration if necessary (Appendix 1) and treat dehydration if present (see Dehydration, Chapter 1).
– Encourage urination, apply warm compresses, treat pain.
– Erection > 4 hours: consider transfusion and refer to surgery.

Prevention of complications

Certain complications can be avoided with appropriate health education of patients/families, routine preventive care and regular follow-up.

Education of patients (including children) and families

Basic knowledge

  • Disease
  • Treatment
  • Monitoring
Chronic, necessarily transmitted by both parents, non-contagious.
Routine (see below) and symptomatic (pain).
Size of the spleen, temperature, baseline Hb.

Major precipitating factors of a painful crisis and how to prevent them

  • Cold
  • Excessive heat
  • Tight clothing
  • Dehydration
  • Excessive effort
  • Infections
Wear warm clothing, avoid bathing in cold water.
For example, avoid going out at mid-day.
Wear wide comfortable clothing without elastics.
Drink plenty of fluids.
Moderate physical activity is beneficial.
Follow routine treatments (including vaccination).

Principal complications requiring the patient to seek urgent medical advice

  • Pain unresponsive to analgesia after 24 hours or severe from the start.
  • Any fever (do not treat at home).
  • Respiratory problems (cough, difficulty breathing, chest pain).
  • Diarrhoea/vomiting and inability to drink.
  • Dehydration (dark, infrequent urine).
  • Anaemia (pale or yellow conjunctivae, pale palms, enlarged spleen).

Routine preventive care

– Prevention of pneumococcal infections
phenoxymethylpenicillin (penicillin V) PO until age 15 years (at least until 5 years):
Children < 1 year: 62.5 mg 2 times daily
Children 1 to < 5 years: 125 mg 2 times daily
Children 5 to 15 years: 250 mg 2 times daily

– Immunization
Ensure that the child’s immunisations are up to date; if not, administer catch up vaccines:

< 5 years

• DTP, hepatitis B, polio, measles, H. influenzae type B vaccines
• Pneumococcal conjugate vaccine (PCV13 or, if not available, PCV10)
• Meningococcal conjugate vaccine in endemic areas
• At 2 years: pneumococcal 23-valent polysaccharide vaccine, at least 8 weeks after the last PCV13 or 10

> 5 years

• DTP or Td, hepatitis B, polio, measles, H. influenzae type B vaccines
Pneumococcal conjugate vaccine PCV13 (or PCV10)
• Meningococcal conjugate vaccine in endemic areas

– To support red blood cell production
folic acid PO6 (life-long treatment)
Children < 1 year: 2.5 mg once daily
Children ≥ 1 year and adults: 5 mg once daily

– Malaria chemoprophylaxis (if malaria prevalence ≥ 5%)
mefloquine PO
Children 6 months to 5 years and > 5 kg: 5 mg base/kg once weekly
Do not use to treat malaria.

– Provide nutritional support at hospital discharge.

Routine follow-up of patients

– Between crises, for information:
Children < 5 years: every 1 to 3 months;
Children ≥ 5 years and adults: every 3 to 6 months.
– After a crisis: as often as necessary, according to the clinical course.

Ref Notes

Critically ill appearing child: weak grunting or crying, drowsy and difficult to arouse, does not smile, disconjugate or anxious gaze, pallor or cyanosis, general hypotonia.

2 For administration by IV route, ceftriaxone powder should to be reconstituted in water for injection only. For administration by IV infusion, dilute each dose of ceftriaxone in 5 ml/kg of 0.9% sodium chloride or 5% glucose in children less than 20 kg and in a bag of 100 ml of 0.9% sodium chloride or 5% glucose in children 20 kg and over and in adults. [ a b c ]
3 Cloxacillin powder for injection should be reconstituted in 4 ml of water for injection. Then dilute each dose of cloxacillin in 5 ml/kg of 0.9% sodium chloride or 5% glucose in children less than 20 kg and in a bag of 100 ml of 0.9% sodium chloride or 5% glucose in children 20 kg and over and in adults.

Always inquire how many transfusions a patient has previously received (risk of iron overload).


Do not transfuse whole blood if possible (risk of fluid overload).

6 Iron is contraindicated in patients who have received multiple transfusions. Avoid combined preparations of iron and folic acid.