## Diagnosis: Aplastic Anemia **Key Point:** Aplastic anemia is the most common cause of pancytopenia with a hypocellular bone marrow in the absence of dysplasia or fibrosis. ### Clinical Features Supporting Aplastic Anemia - Pancytopenia (anemia, leukopenia, thrombocytopenia) - Hypocellular bone marrow (cellularity <25%) - Absence of dysplastic changes or myelofibrosis - Insidious onset over weeks to months - Bleeding manifestations (petechiae) and infection risk ### Differential Diagnosis of Pancytopenia with Hypocellular Marrow | Diagnosis | Marrow Cellularity | Dysplasia | Fibrosis | Key Feature | |-----------|-------------------|-----------|----------|-------------| | **Aplastic anemia** | <25% | Absent | Absent | Pure hypocellularity | | Myelodysplastic syndrome | Variable | Present | May be present | Dysplastic changes | | SLE | Variable | Absent | Absent | Serological markers (ANA, anti-dsDNA) | | TB with marrow involvement | Variable | Absent | Present | Granulomas, acid-fast bacilli | **High-Yield:** Aplastic anemia accounts for approximately 50–70% of pancytopenia cases in developed countries and is the most common acquired cause of pancytopenia globally. ### Pathophysiology Aplastic anemia results from: 1. Destruction of hematopoietic stem cells (immune-mediated in ~70% of cases) 2. Reduced production of all three cell lines 3. Preserved bone marrow architecture (no fibrosis, dysplasia, or infiltration) **Clinical Pearl:** The presence of a hypocellular marrow without dysplasia or fibrosis is the hallmark that distinguishes aplastic anemia from other causes of pancytopenia. **Mnemonic: CAUSAL** — Common causes of aplastic anemia: - **C**hemotherapy / Chloramphenicol - **A**ntibiotics (chloramphenicol, NSAIDs) - **U**nknown (idiopathic, ~50% of cases) - **S**eronegative hepatitis - **A**utoimmune (immune-mediated destruction) - **L**eukemia / Lymphoma (infiltration) [cite:Harrison 21e Ch 109]
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