Aplastic Anaemia

Overview

Pancytopenia (anaemia + leucopenia + thrombocytopenia) from bone marrow aplasia. Defect = too few pluripotent stem cells. One of several hypoproliferative marrow failure states (also: myelophthisic anaemia, pure red cell aplasia, myelodysplastic syndrome).

Causes

50% idiopathic.

Primary: Fanconi’s anaemia (AR, congenital, +skeletal/renal anomalies ± intellectual disability) · immune-mediated acquired (responds to immunosuppression).

Secondary (more common):

Drugs — dose-related (methotrexate, daunorubicin, busulfan, nitrosourea, anthracyclines — recovers on stopping) or idiosyncratic (unpredictable — chloramphenicol = most serious/common; also sulfa drugs, oxyphenbutazone, phenylbutazone, chlorpromazine, gold salts)
Toxic chemicals — benzene, insecticides, arsenicals
Infections — viral hepatitis, EBV, HIV, other viral illness
Misc — SLE, therapeutic X-rays

Clinical features

Anaemia (weakness, fatigue) · haemorrhage (skin, nose, gums, vagina, bowel, rarely CNS/retina — from thrombocytopenia) · mouth/throat infections (neutropenia) · NO lymphadenopathy/hepatosplenomegaly — key negative finding, points away from infiltrative/malignant causes.

Lab findings

Anaemia: normocytic normochromic (occ. macrocytic), reticulocytes low/zero. Leucopenia: granulocytes <1500/µl, relative lymphocytosis, normal neutrophil morphology but high ALP score. Thrombocytopenia: always present.

Marrow: aspirate may give “dry tap” — trephine biopsy essential. Hypocellular/aplastic, fatty replacement, patchy cellularity, severe ↓myeloid+megakaryocyte+erythroid, mostly lymphocytes/plasma cells left. CD34+ stem cells markedly ↓/absent.

Must exclude other pancytopenia causes: MDS, hypersplenism, megaloblastic anaemia (all have normal/↑marrow cellularity, unlike aplastic anaemia), PNH, marrow infiltration (leukaemia/lymphoma/myeloma/mets/storage disease/osteopetrosis/myelofibrosis).

Treatment

Mild = may recover spontaneously. Severe = difficult, younger patients respond better.

General: remove cause + supportive care (transfusion, infection Rx)
Specific: androgens (marrow stimulant), immunosuppression (ATG/ALG ~40-50% success), high-dose steroids, cyclosporine
Splenectomy has NO role (unlike hereditary spherocytosis/ITP)

Clinical relevance

Pancytopenia WITHOUT organomegaly = key clue for aplastic anaemia vs marrow infiltration (leukaemia/lymphoma/mets — which DO show organomegaly). Chloramphenicol = classic prescribing-relevant idiosyncratic cause, restricted for this reason. “Dry tap” on aspirate is itself diagnostic info in the right context, not just technical failure — always follow with trephine biopsy.

Overview

Aplastic anaemia is defined by pancytopenia — simultaneous anaemia, leucopenia, and thrombocytopenia — resulting from aplasia of the bone marrow. The underlying defect in all cases is a sufficient reduction in haematopoietic pluripotent stem cells, leaving too few cells available for division and differentiation. It is one of several hypoproliferative bone marrow failure states (alongside myelophthisic anaemia, pure red cell aplasia, and myelodysplastic syndrome), in which the clinical problem is not anaemia alone but failure across all three cell lines.

Aetiology and Classification

More than half of cases are idiopathic. Where a cause is identified, aplastic anaemia is classified as primary or secondary.

A. Primary aplastic anaemia

Fanconi’s anaemia — autosomal recessive, congenital; often associated with other congenital anomalies (skeletal and renal abnormalities, sometimes intellectual disability).
Immune-mediated (acquired) — immunologic suppression of haematopoietic stem cells, supported by the clinical response to immunosuppressive therapy and by in-vitro marrow culture findings.

B. Secondary aplastic anaemia (more common than primary)

Drugs — either dose-related (predictable, marrow recovers on withdrawal: antimetabolites like methotrexate, mitotic inhibitors like daunorubicin, alkylating agents like busulfan, nitrosourea, anthracyclines) or idiosyncratic (unpredictable individual reaction — the most serious and most common example is chloramphenicol; also sulfa drugs, oxyphenbutazone, phenylbutazone, chlorpromazine, gold salts).
Toxic chemicals — benzene derivatives, insecticides, arsenicals.
Infections — viral hepatitis, Epstein-Barr virus, HIV/AIDS, other viral illnesses.
Miscellaneous — SLE, therapeutic X-irradiation.

Clinical Features

Onset at any age, usually insidious.

Anaemia — progressive weakness, fatigue.
Haemorrhage — from thrombocytopenia: skin, nose, gums, vagina, bowel, occasionally CNS/retina.
Infections — of mouth and throat are common, from neutropenia.
Lymph nodes, liver, and spleen are typically NOT enlarged — a genuinely useful negative finding, since organomegaly points away from aplastic anaemia toward an infiltrative or malignant cause of pancytopenia instead.

Laboratory Findings

Anaemia — normocytic normochromic (occasionally macrocytic); reticulocyte count reduced or zero.
Leucopenia — absolute granulocyte count particularly low (<1500/µL) with relative lymphocytosis; neutrophils are morphologically normal but show a high alkaline phosphatase score.
Thrombocytopenia — always present.
Bone marrow: aspirate may give a “dry tap”; trephine biopsy is essential for diagnosis, showing a hypocellular/aplastic marrow with fatty replacement, patchy residual cellularity, and severe depression of myeloid, megakaryocytic, and erythroid elements, so that the remaining marrow is composed chiefly of lymphocytes and plasma cells. CD34+ haematopoietic stem cells are markedly reduced or absent.

Diagnosis requires excluding the other causes of pancytopenia: myelodysplastic syndrome, hypersplenism, megaloblastic anaemia (all with normal/increased marrow cellularity, unlike aplastic anaemia), paroxysmal nocturnal haemoglobinuria, and marrow infiltration (leukaemia, lymphoma, myeloma, metastatic malignancy, storage disease, osteopetrosis, myelofibrosis).

Treatment Principles

Mild aplasia may recover spontaneously; severe aplastic anaemia is a challenging management problem, with younger patients generally responding better.

General management: identify and eliminate the cause; supportive care with blood/platelet transfusion and treatment/prevention of infection.
Specific treatment: marrow-stimulating agents (oral androgens); immunosuppressive therapy (anti-thymocyte globulin, anti-lymphocyte serum — roughly 40–50% success), high-dose glucocorticoids, or cyclosporine. Splenectomy has no role in aplastic anaemia — an important negative fact, since splenectomy is central to managing several other haematologic conditions (hereditary spherocytosis, ITP) but does nothing for a marrow that has simply stopped producing cells.

Clinical Relevance

The combination of pancytopenia without organomegaly is the single most useful bedside clue pointing toward aplastic anaemia over its main differential — marrow infiltration by leukaemia, lymphoma, or metastatic disease — where hepatosplenomegaly and lymphadenopathy are typically present.
Chloramphenicol as the classic idiosyncratic cause of fatal aplastic anaemia is a directly prescribing-relevant fact, and is why the drug’s systemic use has become restricted despite its broad antibacterial efficacy.
The trephine biopsy requirement (rather than aspirate alone) reflects the fact that a “dry tap” is itself diagnostically informative — a failed aspirate in the right clinical context is a clue to marrow aplasia, not just a technical failure to be repeated.

No Rendered Diagram for This Topic

Aplastic anaemia is a classification-and-features topic (causes, clinical picture, lab findings) rather than a multi-step pathogenic mechanism — the underlying defect (insufficient pluripotent stem cells) is a single-step concept, not a cascade or pathway the sources describe in stages. There is nothing here that a flowchart would clarify beyond the classification tables and comparison points already in notes.md.

Hand-draw suggestion (optional, not a rendered requirement): a simple two-column table — primary causes vs secondary causes, with the dose-related/idiosyncratic drug split noted under secondary — is the most useful revision aid for this topic.