SN4 SHORT NOTE 5M ★ High-yield

Describe aplastic anaemia with its causes, features and investigations.

Pathology · 2nd Professional — Para-Clinical

Definition

Aplastic anaemia is pancytopenia resulting from failure of the haemopoietic stem cells, with a hypocellular marrow replaced by fat and no abnormal infiltrate.

Three features define it — pancytopenia, a hypocellular marrow, and the absence of infiltration, fibrosis or dysplasia
Incidence is two to three times higher in Asia than in the West

Causes

Category	Causes
Idiopathic — about 65%	Immune-mediated destruction of stem cells by cytotoxic T cells
Drugs	Chloramphenicol (idiosyncratic and dose-independent), phenylbutazone, gold, carbamazepine, phenytoin, sulphonamides, antithyroid drugs; cytotoxic chemotherapy (dose-dependent and predictable)
Chemicals	Benzene and other organic solvents; insecticides
Radiation	Whole-body irradiation; radiotherapy
Infection	Viral hepatitis (typically non-A, non-B, non-C), Epstein–Barr virus, HIV, parvovirus (pure red cell aplasia)
Inherited	Fanconi anaemia — autosomal recessive, with short stature, hyperpigmentation, thumb and radial anomalies, renal defects and chromosomal fragility; dyskeratosis congenita
Other	Paroxysmal nocturnal haemoglobinuria; pregnancy; thymoma

Clinical Features

The features follow directly from the three cell lines lost
Anaemia — insidious pallor, fatigue, breathlessness
Thrombocytopenia — petechiae, purpura, bleeding gums, epistaxis, menorrhagia; intracranial haemorrhage is a cause of death
Neutropenia — recurrent infection, mouth ulcers, sore throat; infection is the commonest cause of death
NO hepatosplenomegaly and NO lymphadenopathy — their presence argues strongly against the diagnosis and suggests leukaemia instead

CLINICAL PEARL

The absence of organomegaly is as diagnostic as the pancytopenia itself. Aplastic anaemia is a failure of production, so there is nothing to enlarge the spleen or nodes. Pancytopenia with hepatosplenomegaly points to leukaemia, lymphoma, hypersplenism, or in India to kala-azar — and the distinction is made at the bedside before the marrow is examined.

Investigations

Full blood count — pancytopenia with a low reticulocyte count, which is the key: the marrow is not responding
Peripheral smear — normocytic or macrocytic red cells; NO blasts and no abnormal cells
Bone marrow aspirate and trephine biopsy is essential — aspiration often gives a "dry tap", so the trephine is required to show the hypocellular marrow replaced by fat
Exclude the differentials — leukaemia, myelodysplasia, myeloma, megaloblastic anaemia, hypersplenism, kala-azar, HIV
Flow cytometry for PNH and chromosomal fragility testing in the young

Applied Aspects

Camitta criteria for severe disease — marrow cellularity under 25%, with any two of: neutrophils below 0.5, platelets below 20,000, reticulocytes below 20,000/mm3
Allogeneic stem cell transplantation is curative and is the treatment of choice in the young with a matched sibling donor
Immunosuppression with antithymocyte globulin and ciclosporin for older patients or those without a donor, reflecting the immune pathogenesis
Supportive care determines survival in the short term — irradiated and leucodepleted blood products, prompt treatment of neutropenic fever, and avoidance of aspirin and intramuscular injections
Avoid transfusion from family members if transplantation is a possibility, since it sensitises the recipient against the potential donor
Chloramphenicol is still used in India and remains a preventable cause; its use should always prompt consideration of this diagnosis

All questions in Haematology I: Anaemias & Red-cell Disorders

Every Pathology chapter →