Progressive bone marrow failure, resulting in pancytopenia. In some cases, there are identifiable factors such as drugs, chemicals, radiation and certain infections, but in a proportion of cases, no obvious cause is found.
The anaemia appears to be mediated by aberrant cytokine expression by T-cells, inhibiting haematopoiesis. Improvement with immunosuppressive treatments (usually ciclosporin and anti-thymocyte globulin) support an autoimmune cause, possibly following a trigger. Haematopoietic stem cell transplantation is second-line treatment.
International Agranulocytosis and Aplastic Anaemia Study Group (1987):
- At least 2 lineages affected in peripheral blood:
- Haemoglobin <10g
- Neutrophils <1.5
- Platelets <50
- Bone marrow:
- Cellularity <30% (not applicable to older individuals)
- Absence of dysplasia or bone marrow fibrosis.
Other diagnoses to consider/exclude:
- Hypoplastic myelodysplastic syndrome
- Infections (typically viral)
- Bone marrow fibrosis (e.g. secondary to malignancy)
- Inherited marrow failure syndromes, e.g. Fanconi's anaemia, Blackfan-diamond anaemia, etc.
- Paroxysmal nocturnal haemoglobinuria (may overlap with aplastic anaemia - about half of patients with AA have a PNH clone)
- Non-severe AA
- Decreased bone marrow cellularity and peripheral blood cytopenia, not fulfilling criteria for SAA
- Severe AA
- Bone marrow cellularity <25%. 2 or more of following: neutrophil count <0.5 × 109/l, platelet count <20 × 109/l, reticulocyte count <20 × 109/l.
- Very severe AA
- Criteria of severe AA and neutrophil count <0.2 × 109/l
- ↑ Dunn DE, Tanawattanacharoen P, Boccuni P, Nagakura S, Green SW, Kirby MR, Kumar MS, Rosenfeld S, Young NS. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Annals of internal medicine. 1999 Sep 21; 131(6):401-8.
- ↑ Camitta BM, Thomas ED, Nathan DG, Santos G, Gordon-Smith EC, Gale RP, Rappeport JM, Storb R. Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality. Blood. 1976 Jul; 48(1):63-70.
- ↑ Bacigalupo A, Hows J, Gluckman E, Nissen C, Marsh J, Van Lint MT, Congiu M, De Planque MM, Ernst P, McCann S. Bone marrow transplantation (BMT) versus immunosuppression for the treatment of severe aplastic anaemia (SAA): a report of the EBMT SAA working party. British journal of haematology. 1988 Oct; 70(2):177-82.