A 38-year-old woman presents with progressive fatigue, recurrent infections, and spontaneous bruising for 3 weeks. Full blood count reveals hemoglobin 8.2 g/dL, WBC 2.1 × 10⁹/L, and platelets 45 × 10⁹/L. Reticulocyte count is 0.8%. Which investigation is most appropriate to establish the diagnosis of aplastic anemia?

## Diagnostic Approach to Pancytopenia with Suspected Aplastic Anemia ### Clinical Context The patient presents with pancytopenia (anemia, leukopenia, thrombocytopenia) with a low reticulocyte count, suggesting bone marrow failure rather than peripheral destruction or hemolysis. ### Why Bone Marrow Examination is the Gold Standard **Key Point:** Bone marrow aspiration and trephine biopsy is the definitive investigation for aplastic anemia diagnosis. It demonstrates: - Hypocellular marrow (cellularity <25%) - Absence of dysplasia - Absence of fibrosis - Absence of infiltration ### Diagnostic Criteria for Aplastic Anemia | Finding | Significance | |---------|-------------| | Hypocellular marrow (<25% cellularity) | Diagnostic hallmark | | Low reticulocyte count | Indicates inadequate bone marrow response | | Absence of dysplasia | Excludes MDS | | Absence of fibrosis | Excludes primary myelofibrosis | | Normal cytogenetics | Excludes clonal disorders | ### Workup Algorithm for Pancytopenia ```mermaid flowchart TD A[Pancytopenia confirmed]:::outcome --> B{Reticulocyte count?}:::decision B -->|Low/Normal| C[Bone marrow failure suspected]:::outcome B -->|High| D[Hemolysis/Peripheral destruction]:::outcome C --> E[Bone marrow aspiration & trephine]:::action E --> F{Cellularity?}:::decision F -->|Hypocellular| G[Aplastic anemia]:::outcome F -->|Normocellular + dysplasia| H[Myelodysplastic syndrome]:::outcome F -->|Fibrosis| I[Primary myelofibrosis]:::outcome ``` **High-Yield:** The combination of pancytopenia + low reticulocyte count + hypocellular marrow = aplastic anemia until proven otherwise. **Clinical Pearl:** Trephine biopsy is essential because it assesses cellularity and architecture; aspiration alone may miss focal hypocellularity or fibrosis. ### Next Steps After Diagnosis Once aplastic anemia is confirmed, cytogenetic analysis and flow cytometry are performed to: - Exclude clonal evolution (PNH, MDS) - Assess for cytogenetic abnormalities (poor prognostic marker) - Guide treatment (immunosuppression vs. transplant)