Sickle Cell Anaemia

Caused by homozygous inheritance of the haemoglobin S (HbS) gene. Distorted, inflexible red cells adhere to vascular endothelium and plug small arterioles/capillaries, causing infarction; vaso-occlusion also injures the endothelium, causing inflammation and thrombosis. Sickled cells are fragile, so the mechanical trauma of circulation causes haemolysis. Chronic compensatory marrow hyperactivity deforms the bones.

Clinical features

Anaemia, mild jaundice, pallor. Hepatosplenomegaly is common in children — repeated infarction/fibrosis (autosplenectomy) means the spleen is commonly atrophied by adulthood. Cardiomegaly and systolic ejection murmurs are common. Cholelithiasis, and chronic punched-out ankle ulcers, are common.

Acute exacerbations (crises)

Occur intermittently, often for no known reason — precipitated by fever, viral infection, or local trauma.

• Vaso-occlusive (pain) crisis — the most common type, from ischaemia/tissue hypoxia/infarction, typically of bone but also spleen, lungs, or kidneys. Severe pain in long bones, hands/feet, back, and joints; hip pain may reflect avascular necrosis of the femoral head.
• Aplastic crisis — marrow erythropoiesis slows during acute parvovirus infection, causing acute erythroblastopenia.
• Acute chest syndrome — pulmonary microvascular occlusion; a common cause of death (up to 10% mortality), most common in childhood; repeated episodes predispose to chronic pulmonary hypertension. Sudden fever, chest pain, pulmonary infiltrates; may follow bacterial pneumonia; hypoxaemia can develop rapidly.
• Sequestration crisis — in children, acute splenic sequestration of sickled cells can exacerbate anaemia; hepatic sequestration with rapid liver enlargement can also occur.
• Priapism — a serious complication that can cause erectile dysfunction, most common in young men.

Complications

Chronic splenic damage causes autoinfarction and increased susceptibility to infection (particularly pneumococcal and Salmonella). Recurrent ischaemia/infarction can cause chronic multi-organ dysfunction — ischaemic stroke, seizures, avascular necrosis of the hips, renal concentrating defects, chronic kidney disease, heart failure, pulmonary hypertension/fibrosis, and retinopathy.

Diagnosis

• DNA testing (prenatal and newborn screening).
• Peripheral smear: normocytic, nucleated RBCs, reticulocytosis, sickled (crescent-shaped) cells.
• Haemoglobin electrophoresis: HbS.

Evaluating exacerbations:

• Aplastic crisis: reticulocyte count < 1% (especially with Hb below the patient’s usual level) is suggestive.
• Painful crisis: WBC often rises with a left shift, particularly with bacterial infection.
• Acute chest syndrome: the leading cause of death in sickle cell disease — consider pulmonary embolism too if chest pain/dyspnoea. Hypoxaemia with pulmonary infiltrates on CXR suggests acute chest syndrome/pneumonia; hypoxaemia without infiltrates suggests PE.

Management

IV antibiotics for infection; analgesia and IV hydration for vaso-occlusive pain crisis; transfusion; immunisation, folate supplementation, and hydroxyurea for ongoing health maintenance. Haematopoietic stem cell transplant has historically been the only curative option — since December 2023, gene therapies Casgevy (exagamglogene autotemcel, CRISPR-based) and Lyfgenia (lovotibeglogene autotemcel) offer a curative alternative for eligible patients ≥12 years, though at extremely high cost (~US$2.2–3.1 million) and not yet in routine Australian use.

Prognosis

Life expectancy in homozygous patients has steadily risen to > 50 years. Common causes of death: acute chest syndrome, intercurrent infection, pulmonary emboli, infarction of a vital organ, chronic kidney disease.