A 38-year-old woman presents with progressive fatigue, recurrent infections, and spontaneous bruising for 3 weeks. Full blood count shows hemoglobin 7.2 g/dL, WBC 2.1 × 10⁹/L, and platelets 45 × 10⁹/L. Reticulocyte count is 0.8%. Which is the investigation of choice to confirm the underlying diagnosis?

Explanation

## Diagnosis: Pancytopenia with Low Reticulocyte Count The clinical presentation of pancytopenia (anemia, leukopenia, thrombocytopenia) with a **low reticulocyte count** (0.8%, normal 0.5–2.5% but inadequate for the degree of anemia) indicates **bone marrow failure** rather than peripheral destruction. ## Investigation of Choice: Bone Marrow Examination **Key Point:** Bone marrow aspiration and trephine biopsy is the gold standard for evaluating pancytopenia with suspected marrow failure. It directly visualizes: - Cellularity (hypocellular vs. normocellular vs. hypercellular) - Dysplastic changes (MDS) - Infiltrative lesions (leukemia, lymphoma, granulomas, fibrosis) - Megaloblastic changes (B12/folate deficiency) - Storage disorders ## Diagnostic Algorithm ```mermaid flowchart TD A[Pancytopenia]:::outcome --> B{Reticulocyte count}:::decision B -->|High| C[Peripheral destruction]:::outcome C --> D[Peripheral smear, coagulation studies]:::action B -->|Low| E[Bone marrow failure]:::outcome E --> F[Bone marrow aspiration + trephine]:::action F --> G{Cellularity & morphology}:::decision G -->|Hypocellular| H[Aplastic anemia]:::outcome G -->|Dysplasia| I[MDS]:::outcome G -->|Infiltration| J[Leukemia/Lymphoma]:::outcome ``` **High-Yield:** The **reticulocyte count is the key discriminator**: - Low reticulocyte count → bone marrow failure → **bone marrow biopsy** - High reticulocyte count → peripheral destruction → smear, coagulation studies **Clinical Pearl:** Trephine biopsy is superior to aspiration alone because it preserves architecture and detects fibrosis (aplastic anemia, myelofibrosis) that aspiration may miss. [cite:Harrison 21e Ch 109]