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Q1: Definition and diagnosis (2 min)
- Define aplastic anaemia. (Pancytopenia with a hypocellular marrow under 25 percent, no abnormal infiltrate or dysplasia.)
- Why is the trephine biopsy essential and the aspirate alone unreliable? (Aspirate may be dilute/misleading; trephine assesses true cellularity.)
- How is it distinguished from hypoplastic MDS? (Dysplasia, clonal cytogenetics — monosomy 5/7, trisomy 8 — and raised CD34 blasts favour MDS.)
- What is the role of flow cytometry at diagnosis? (Detect a small PNH clone — FLAER/CD55-CD59 — in up to half of acquired cases.)
Q2: Severity grading (2 min)
- State the Camitta criteria for severe AA verbatim. (Cellularity under 25 percent plus at least two of neutrophils under 0.5, platelets under 20, reticulocytes under 20 x 10^9/L.)
- What defines very severe AA? (Neutrophils under 0.2.)
- Why does severity grading matter? (Drives the choice between HSCT and IST.)
Q3: Management (3 min)
- First-line definitive therapy in a 25-year-old with a matched sibling donor? (Allogeneic HSCT.)
- First-line therapy in a 55-year-old with no sibling donor? (Horse ATG plus ciclosporin; add eltrombopag in selected protocols.)
- Horse ATG dose and schedule? (40 mg/kg/day IV for 4 days, with premedication and test dose.)
- Ciclosporin dose, target level, duration? (5 mg/kg/day orally; trough 200 to 400 micrograms/L; at least 6 months after maximal response, then taper over 1 to 2 years.)
- Why is horse ATG preferred over rabbit ATG? (Scheinberg NEJM 2011 — horse ATG superior.)
- How do you manage neutropenic fever? (Cultures, empirical IV antibiotics within 1 hour.)
Q4: Pathophysiology (2 min)
- What is the dominant mechanism? (Autoimmune T-cell-mediated destruction of CD34+ stem cells.)
- Name the key cytokines. (Interferon-gamma and tumour necrosis factor-alpha.)
- How does this explain the response to IST? (Removing the T-cell clone lets surviving stem cells repopulate.)
- Role of telomere biology? (Short telomeres from TERT/TERC/DKC1 mutations identify a subset with worse outcome and higher clonal risk.)
Q5: Complications and prognosis (2 min)
- Early causes of death? (Infection and bleeding.)
- Late complications? (Clonal evolution to PNH, MDS, AML — especially monosomy 7; transfusional iron overload; post-HSCT GVHD, secondary malignancy.)
- Prognosis with HSCT vs IST? (HSCT matched sibling 80 to 90 percent long-term survival; IST 60 to 70 percent response, 70 to 85 percent 5-year survival, 10 to 15 percent clonal evolution at 10 years.)
- What lifelong surveillance is needed? (Blood counts and PNH flow cytometry every 6 to 12 months.)