How do I differentiate between aplastic anaemia and other causes of bone marrow failure in primary care?

Guideline-aligned answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MRCGP.

Posted: 22 August 2025Updated: 22 August 2025 Guideline-Aligned (High Confidence) Clinically Reviewed
Dr Kola Tytler MBBS CertHE MBA MRCGPClinical Lead • iatroX

In a primary care setting, differentiating aplastic anaemia (AA) from other causes of bone marrow failure primarily relies on clinical suspicion and initial blood tests, as definitive diagnosis requires specialist referral and bone marrow examination . Key clinical features include pancytopenia symptoms such as fatigue, infections, and bleeding tendencies without organomegaly or lymphadenopathy, which are more typical of malignancies like leukaemia . Initial blood tests should show pancytopenia with low reticulocyte count, indicating marrow hypoplasia rather than peripheral destruction or sequestration . Peripheral blood smear typically reveals normocytic, normochromic anaemia without abnormal cells, helping to exclude myelodysplastic syndromes or leukaemia . Other causes of bone marrow failure such as myelophthisis, infiltrative diseases, or nutritional deficiencies often present with additional clinical or laboratory clues, including organomegaly, abnormal cell morphology, or macrocytosis . Referral for urgent haematology assessment is essential for bone marrow biopsy to confirm hypocellularity without fibrosis or malignant infiltration, which is diagnostic of AA . Thus, in primary care, the differentiation hinges on recognising unexplained pancytopenia with hypocellular marrow features suggested by blood tests and clinical context, followed by prompt specialist referral .

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