Synopsis
Recognise hypocellular marrow failure, exclude reversible and clonal mimics, stabilise infection and bleeding, and choose transplant or immunosuppression according to severity, age and donor status.
- Aplastic anaemia is pancytopenia caused by failure of haematopoietic stem and progenitor cells in a hypocellular marrow without malignant replacement or substantial fibrosis.
- Most acquired cases are immune mediated and idiopathic; implicated exposures include medicines, toxins, hepatitis and other infections, while inherited marrow-failure syndromes require active consideration.
- Patients present through consequences of low cell lines: fatigue and dyspnoea, infection or mouth ulceration, petechiae, bruising and mucosal bleeding.
- Splenomegaly, lymphadenopathy, marked dysplasia or constitutional bone pain is atypical and should broaden assessment to malignancy, infiltration, hypersplenism or another diagnosis.
- The blood count, reticulocytes and film identify pancytopenia with an inappropriately low reticulocyte response; marrow aspirate and trephine establish hypocellularity and exclude clonal disease.
- Severity classification uses marrow cellularity plus neutrophil, platelet and reticulocyte thresholds and must be calculated from validated local measurements by haematology.
- Flow cytometry for a PNH clone and cytogenetic or molecular studies help define overlap and exclude hypoplastic myelodysplasia, but a small PNH clone does not itself mean classical haemolytic PNH.
- Younger fit patients with severe disease and a matched sibling donor may proceed to allogeneic stem-cell transplantation; others commonly receive antithymocyte globulin plus ciclosporin-based immunosuppression.
- Eltrombopag may be combined with specialist immunosuppression or used in selected refractory disease under current NHS pathways, with liver and clonal monitoring.
- Supportive care includes infection treatment, carefully selected transfusion, bleeding prevention and avoidance of unnecessary marrow-toxic medicines while definitive therapy is arranged.
Key red flags
Hypotension, confusion, hypoxia or fever with profound neutropenia requires empirical antibiotics and resuscitation before diagnostic completion.
Investigation priorities
Confirm cytopenias and quantify marrow output.
Management branches
New pancytopenia includes severe neutropenia, thrombocytopenia or symptomatic anaemia.
- Admit unstable or severely cytopenic patients, culture suspected infection and deliver the local neutropenic-sepsis antibiotic regimen without waiting for marrow biopsy.
- Discuss platelet and red-cell support with haematology and transfusion medicine, using appropriately selected components and minimising avoidable donor exposure before transplant.
- Stop plausible marrow-toxic exposure after senior review, institute bleeding and infection precautions and avoid rectal procedures or intramuscular injections when unsafe.
Key medicines
Horse antithymocyte globulinA common adult severe-aplastic-anaemia regimen is 40 mg/kg intravenously once daily for 4 days, given in a specialist centre with corticosteroid reaction prophylaxis and ciclosporin when indicated.Infusion reactions, serum sickness, anaphylaxis, infection and worsening cytopenias require monitored administration; product selection and viral screening follow the centre protocol.
CiclosporinA specialist commonly starts about 5 mg/kg/day orally in 2 divided doses, then adjusts to the centre's trough target, renal function, blood pressure and interactions. Taper only after a sustained haematological response.Nephrotoxicity, hypertension, magnesium loss, neurotoxicity, infection and numerous CYP3A interactions require laboratory and clinical surveillance; abrupt early withdrawal promotes relapse.