Haematological disease in a child: Sickle cell disease (SCD) Flashcards
Define SCD?
Genetic condition with abnormal sickle-shaped red blood cells secondary to haemoglobin S (Hb S) production instead of haemoglobin A.
Explain the aetiology/risk factors for SCD?
Autosomal recessive inherited point mutation in the b-globin gene resulting in a substitution of valine for glutamic acid on position 6, producing the abnormal protein, haemoglobin S. Disease depends on the karyotype: homozygous Hb S (sickle cell anaemia), heterozygous HbS (sickle cell trait), heterozygous Hb S and Hb C, Hb S, b-thalassaemia (sickle cell disease).
With deoxygenation, Hb S has decreased solubility, increased viscosity and polymer formation at concentrations exceeding 30 g/dl. Reduced RBC survival (20/7; normal 120/7) secondary to sequestration and destruction.
Summarise the epidemiology of SCD.
Malaria-prevalent countries. 1/1000 (UK). Manifests >6/12 old (Hb-F in <6/12). Common (5–12%) in African, Caribbean and Middle Eastern areas.
What are presenting signs and symptoms predisposing a crisis?
Infection, temperature change, dehydration.
What are presenting signs and symptoms of a thrombocytic crisis?
Severe abdominal pain (mimics acute abdomen), acute chest syndrome (SOB, cough, pain, pyrexia), severe bony tenderness and swelling especially of the small bones in hands and feet (avascular necrosis may follow), priapism.
What are presenting signs and symptoms of an aplastic crisis?
Secondary to parvovirus B19 infection of RBC progenitors causing temporary cessation of erythropoiesis and RBC lifespan shorten to 10–20/7. Characterised by sudden lethargy and pallor secondary to sudden decreased Hb.
What are presenting signs and symptoms of splenic sequenstration crises?
Sickled RBC pools in spleen, leading to sudden rapid enlargement, repeated splenic infarction, impaired splenic function (immunodeficiency). Repeated events cause splenic fibrosis and hypoplasia (autosplenectomy).
What are appropriate investigations for SCD?
Bloods: Low Hb, high reticulocytes in haemolytic crisis, low reticulocytes in aplastic crisis, U&Es.
Blood film: Sickle cells, anisocytosis, features of hyposplenism (target cells, Howell-Jolly bodies).
Haemoglobin electrophoresis: Hb S, absence of Hb A (in Hb SS) and increased levels of Hb F.
What is the management of an acute crisis?
- O2
- IV fluids with fluid resuscitation
- Opiate analgesia
- Antibiotics
What is the management for infection prophylaxis?
- Penicillin V OD
- Pneumococcal
- Meningococcal
- Hib vaccination
What is the management for general SCD?
Folic acid: For increased cell turnover.
Hydroxurea: Inhibitor of deoxynucleotide synthesis; increases Hb F levels and reduces frequency and duration crisis.
RBC transfusion: Maintain Hb S level to <30%. Iron chelators are required for those who have frequent transfusions.
Exchange transfusion: In sequestration crisis and before surgery.
Advice: Nutrition, genetic counselling, prenatal diagnosis.
Bone marrow transplantation: Allogenic BMT can effect cure (dependent on suitable donor and risk:benefit ratio)/cord blood stem cell transplantation.
Surgery: Limited to disease complications treatment (AVN-joint replacements, skin graft for chronic leg ulcers, laparoscopic cholecystectomy).
What are some complications associated with SCD?
Increased risk of infections with encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae, meningococcus, Salmonella) secondary to autosplenectomy. Gallstones, renal papillary necrosis, leg ulcers, cardiomyopathy and cerebral infarction.
What is the prognosis of SCD?
Major mortality in children is usually the result of infection. Lifespan generally good dependent on complications.
