A 38-year-old woman presents with fatigue, recurrent infections, and spontaneous bruising for 3 weeks. CBC shows hemoglobin 7.2 g/dL, WBC 2100/μL, and platelets 45,000/μL. Bone marrow biopsy reveals hypocellular marrow with 5% blasts. In the diagnostic workup of pancytopenia, all of the following are appropriate initial investigations EXCEPT:

## Initial Diagnostic Approach to Pancytopenia ### Appropriate First-Line Investigations **Key Point:** The workup of pancytopenia aims to distinguish between bone marrow failure (aplasia, infiltration, dysplasia) and peripheral destruction/sequestration. | Investigation | Purpose | Rationale | |---|---|---| | Reticulocyte count & PBS | Assess marrow response | Low reticulocyte count suggests marrow failure; morphology guides diagnosis | | Vitamin B12 & folate | Identify megaloblastic causes | Deficiency causes macrocytic pancytopenia with hypercellular marrow | | LDH & uric acid | Screen for hemolysis/tumor lysis | Elevated LDH suggests hemolysis; high uric acid indicates high cell turnover | | Bone marrow biopsy | Direct assessment | Gold standard to differentiate aplasia, dysplasia, infiltration, fibrosis | ### Why HLA-B5801 Genotyping Is NOT Part of Initial Pancytopenia Workup **High-Yield:** HLA-B5801 testing is a **pharmacogenomic screening** performed *before initiating allopurinol therapy* in at-risk populations (especially Han Chinese, Thai, Korean ancestry), not as part of the diagnostic investigation of pancytopenia itself. **Clinical Pearl:** HLA-B5801 positivity is associated with severe cutaneous adverse reactions (SCAR) and allopurinol hypersensitivity syndrome — it is a *preventive measure* for drug selection, not a diagnostic test for the cause of pancytopenia. **Tip:** Do not confuse *therapeutic drug selection* (HLA-B5801 testing) with *diagnostic workup* (B12, folate, LDH, reticulocyte count). The question asks what belongs in the diagnostic algorithm, not in subsequent management. ### Correct Sequence of Pancytopenia Investigation 1. **Clinical history** — drugs, infections, autoimmune disease, family history 2. **CBC with differential** — severity, RBC indices (macro vs normocytic) 3. **Reticulocyte count** — marrow response (low = failure; high = peripheral loss) 4. **Peripheral blood smear** — dysplastic changes, blasts, schistocytes 5. **B12 & folate levels** — rule out megaloblastic anemia 6. **LDH, bilirubin, haptoglobin** — screen for hemolysis 7. **Bone marrow biopsy** — definitive diagnosis (aplasia, dysplasia, infiltration, fibrosis) 8. **Cytogenetics & flow cytometry** — if dysplasia or blasts present [cite:Harrison 21e Ch 110]