Functional Asplenia in Sickle Cell Disease

Functional asplenia in sickle cell disease is loss of splenic filtering and immune function through repeated sickling, vaso occlusion and infarction. Most children with sickle cell anaemia are functionally asplenic by 5 years of age, and some from 6 months, which makes overwhelming bacterial infection the leading early cause of death.

Risk is highest under 5 years. Pathogens are mainly Streptococcus pneumoniae, then Haemophilus influenzae type b, Neisseria meningitidis and Salmonella species. Malaria is an additional major risk in endemic regions.

Sickle cell anaemia (HbSS and HbSβ0 thalassaemia) is affected earliest. Children with haemoglobin SC disease keep splenic function longer, though many become hyposplenic later.

Pathophysiology.

Repeated sickling in the spleen's slow circulation causes microvascular occlusion and infarction. The spleen first enlarges and can sequester blood, and later shrinks to a fibrotic remnant (autosplenectomy).

Loss of splenic macrophage clearance of encapsulated bacteria and loss of marginal zone B cells reduce antibody production against polysaccharide antigens.

• Fever may be the only sign of overwhelming sepsis. Deterioration to shock can occur within hours.
• Splenomegaly in infants and toddlers, with acute splenic sequestration presenting as rapid splenic enlargement, pallor and shock.
• Later: a small, impalpable spleen.

Red flags.

• Temperature of 38.5 degrees Celsius or higher (or 38.0 degrees with unwell appearance) in any child with sickle cell disease.
• Lethargy, pallor, tachycardia, poor perfusion or rapid fall in haemoglobin.
• Meningism, severe headache, or acute chest syndrome.

• Blood film: Howell-Jolly bodies, target cells and pitted red cells indicate hyposplenia. Radionuclide spleen scan or ultrasound can confirm absent function but is rarely needed.
• During febrile illness: full blood count with differential, reticulocytes, blood culture, urinalysis and culture, C-reactive protein, and chest X-ray if respiratory signs. Lumbar puncture if meningitis is suspected and the child is stable. Malaria test where endemic.

Differential diagnosis. Viral illness, malaria, osteomyelitis (including Salmonella), acute chest syndrome, aplastic crisis, splenic sequestration and vaso occlusive crisis.

Prevention.

• Phenoxymethylpenicillin prophylaxis from 2 to 3 months of age: 62.5 mg twice daily under 1 year, 125 mg twice daily from 1 to 5 years, and 250 mg twice daily over 5 years. Continue to at least 5 years, and often lifelong in regions with high rates of resistant organisms or limited access to care. Use alternatives such as erythromycin in penicillin allergy.
• Immunise with conjugate pneumococcal vaccine, then the 23-valent polysaccharide vaccine at 2 years with a booster at 5 years, Haemophilus influenzae type b, quadrivalent meningococcal (A, C, W, Y) and serogroup B vaccines, and annual influenza vaccine.
• Malaria chemoprophylaxis in endemic regions, and use of bed nets.
• Hydroxyurea started early (from 9 months) lowers sickling and may preserve splenic function.
• Teach parents to check temperature and to seek urgent review for any fever.

Fever.

• Urgent medical review, blood cultures, and a full blood count within 1 hour.
• Ceftriaxone 80 mg/kg IV (maximum 4 g) once daily after cultures without waiting for results. Admit if the child is unwell, temperature is 40 degrees Celsius or over, haemoglobin is falling, white cell count is under 5 or over 30 x 10^9/L, or there is no reliable follow up.
• Treat malaria, acute chest syndrome and osteomyelitis as indicated.

Acute splenic sequestration. Resuscitate with 0.9% sodium chloride 10 mL/kg and cross-matched red cell transfusion 5 to 10 mL/kg slowly, avoiding over transfusion because trapped cells release as the spleen reduces. Consider splenectomy after recurrent episodes.

Monitoring. Vaccine status, adherence to penicillin, infection record, spleen size and haemoglobin.

Referral and escalation. Care should be shared with a haematology service, with an emergency plan for the child and family.