Define Aplastic Anaemia. Describe its causes, clinical features, investigations and complications.

Definition

• Aplastic anaemia is pancytopenia (anaemia + leucopenia + thrombocytopenia) with a hypocellular ('empty') bone marrow, due to failure of the haematopoietic stem cells.
• There is no abnormal infiltration or organomegaly.

Causes

• Acquired — idiopathic (commonest), drugs/toxins (chloramphenicol, chemotherapy, benzene), radiation, viral (hepatitis, EBV), immune-mediated.
• Inherited — Fanconi anaemia (with short stature, café-au-lait spots, radial/thumb anomalies), dyskeratosis congenita.

Clinical Features

• Anaemia (pallor, fatigue), thrombocytopenia (bruising, bleeding) and neutropenia (infections).
• No hepatosplenomegaly or lymphadenopathy — an important point distinguishing it from leukaemia.

Investigations & Management

• Pancytopenia with a low reticulocyte count; bone-marrow biopsy shows a hypocellular marrow replaced by fat.
• Supportive care — red-cell and platelet transfusions, prompt treatment of infections.
• Immunosuppression (antithymocyte globulin + cyclosporine) and haematopoietic stem-cell transplantation (curative) for severe disease.

Assessing Severity

• Severity graded by the degree of neutropenia, thrombocytopenia and reticulocytopenia.
• Very low neutrophils/platelets/reticulocytes define severe aplastic anaemia — an indication for urgent definitive therapy.

Complications

• Life-threatening infection (neutropenia) and haemorrhage (thrombocytopenia).
• Iron overload from repeated transfusions; and, in inherited forms, a risk of evolving into leukaemia.

Prognosis

Severe aplastic anaemia is life-threatening without treatment; outcomes have improved greatly with early stem-cell transplantation (best in young patients with a matched sibling donor) or immunosuppressive therapy.

Differential Diagnosis

• Leukaemia (hypercellular marrow with blasts), marrow infiltration, and hypersplenism.
• Megaloblastic anaemia and overwhelming infection can also cause pancytopenia.

Absent reticulocytes with pancytopenia point to marrow failure.