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PA17.1 | Aplastic Anaemia & Bone Marrow Examination — Part 2

Clinical Features

Onset is insidious over weeks to months, with features driven by the three-lineage failure:

Lineage	Effect	Symptoms
Erythrocytes ↓	Anaemia	Fatigue, pallor, dyspnoea on exertion
Neutrophils ↓	Immunosuppression	Recurrent bacterial/fungal infections
Platelets ↓	Thrombocytopenia	Petechiae, ecchymoses, mucosal bleeding

Physical examination:
- Pallor, petechiae, purpura
- Signs of infection
- No hepatomegaly, no splenomegaly, no lymphadenopathy — the hallmark negative finding

Camitta Severity Criteria (used to guide treatment):
- Severe aplastic anaemia (SAA): hypocellular marrow (<25%) PLUS two of three: neutrophils <0.5×10⁹/L, platelets <20×10⁹/L, reticulocytes <20×10⁹/L
- Very severe (vSAA): SAA criteria with neutrophils <0.2×10⁹/L
- Non-severe/moderate: cytopenias not meeting the above thresholds

SAA/vSAA = stem cell transplant if donor available; otherwise immunosuppression.

Peripheral Blood Findings

The peripheral smear in aplastic anaemia is characteristically depleted but morphologically normal:

Pancytopenia — low RBC count, leucocyte count, and platelet count
Normocytic-normochromic anaemia — MCV and MCHC are normal; contrast with macrocytosis in megaloblastic anaemia
Low or absent reticulocytes (reticulocytopenia) — confirms impaired erythropoiesis; a key finding distinguishing aplasia from haemolysis
Leucocytes: reduced in total; the differential shows relative lymphocytosis (lymphocytes are spared because they are mature, not stem-cell–derived)
Platelets: reduced in number; those present are normal in size
No blasts, no hypersegmented neutrophils, no teardrop cells

The absence of abnormal cells on the smear is as important as the cytopenias.

Three-panel comparison showing normal blood smear, aplastic anemia blood smear with reduced cell density, and laboratory value comparisons. — **Panel A:** Normal peripheral blood smear showing typical cell density and distribution of RBCs, WBCs, and platelets. **Panel B:** Aplastic anemia smear demonstrating pancytopenia with normocytic-normochromic RBCs, reduced platelets, and absence of blasts. **Panel C:** Laboratory parameters comparing normal values with aplastic anemia findings including hemoglobin, total leukocyte count, platelet count, and reticulocyte percentage.

SELF-CHECK

A 22-year-old male has Hb 6.2 g/dL, TLC 1,600/µL, platelets 18,000/µL. Peripheral smear shows normocytic-normochromic RBCs, reduced platelets, no blasts, no hypersegmented neutrophils, relative lymphocytosis. Reticulocyte count is 0.1%. What is the MOST likely diagnosis?

A. Megaloblastic anaemia

B. Aplastic anaemia

C. Acute lymphoblastic leukaemia

D. Hypersplenism

Reveal Answer

Answer: B. Aplastic anaemia

Aplastic anaemia presents with pancytopenia, normocytic-normochromic RBCs, reticulocytopenia, and NO blasts or hypersegmented neutrophils. Megaloblastic anaemia causes macrocytosis and hypersegmented neutrophils. ALL would show blasts on the smear. Hypersplenism rarely causes this degree of anaemia and typically shows splenomegaly on examination.

Differential Diagnosis

Pancytopenia is the common presentation; the bone marrow findings and clinical context separate the diagnoses:

Condition	Marrow appearance	Key distinguishing features
Aplastic anaemia	Hypocellular, fat-replaced, no abnormal cells	No organomegaly; normal cell morphology on smear
Hypocellular MDS	Hypocellular but dysplastic cells present	Dysplastic neutrophils, ring sideroblasts, cytogenetic abnormalities
Aleukemic leukaemia	Packed with blasts; crowded	Blasts present (may be few on smear but numerous in marrow)
Megaloblastic anaemia	Hypercellular; megaloblasts, giant metamyelocytes	Macrocytosis, hypersegmented neutrophils; B12/folate deficiency
Myelofibrosis	Fibrosis on silver stain; dry tap	Tear-drop poikilocytes, splenomegaly

Practical point: Hypocellular MDS and aplastic anaemia can be impossible to distinguish on marrow morphology alone; cytogenetics and flow cytometry are required in ambiguous cases.