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Stem
A 19-year-old male college student presents to the emergency department with a 4-week history of progressive fatigue, recurrent epistaxis and gum bleeding, and a 3-day history of fever with a sore throat. He takes no regular medication and has had no recent foreign travel. On examination he is pale, afebrile (38.2 degrees C), with widespread petechiae over the lower limbs and buccal mucosa. There is no lymphadenopathy, no hepatosplenomegaly. Blood count: haemoglobin 58 g/L, neutrophils 0.2 x 10^9/L, platelets 9 x 10^9/L, reticulocytes 8 x 10^9/L, MCV 98 fL. Peripheral film shows no abnormal cells or blasts. Bone marrow trephine: cellularity 12 percent, with no abnormal infiltrate or dysplasia.
Questions
a) What is the diagnosis and what is its severity grade? Give the criteria you used. (3 marks)
Diagnosis: severe (very severe) acquired aplastic anaemia — pancytopenia with a hypocellular marrow and no abnormal cells. Severity grade: very severe AA, because the patient meets the Camitta severe criteria (cellularity under 25 percent plus at least two of neutrophils under 0.5, platelets under 20, reticulocytes under 20) AND the neutrophil count is under 0.2 x 10^9/L.
b) Outline the first-line investigations to confirm the diagnosis and exclude mimics. (3 marks)
Full blood count and film; reticulocyte count; bone marrow aspirate and trephine biopsy (hypocellularity, no blasts/dysplasia/infiltrate); cytogenetics (normal in idiopathic AA; clonal abnormalities suggest MDS); flow cytometry for a PNH clone (FLAER, CD55/CD59); vitamin B12 and folate; copper level; viral serology (hepatitis A/B/C, EBV, CMV, HIV, parvovirus B19 PCR); autoimmune screen; HLA typing of the patient and siblings; telomere length / germline testing if an inherited syndrome is suspected.
c) Outline the definitive management, including how the choice depends on his clinical features. (3 marks)
He is under 40 years old: if he has an HLA-matched sibling donor, the first-line definitive treatment is allogeneic haematopoietic stem cell transplant (curative; long-term survival about 80 to 90 percent in young patients). If no matched sibling donor, treat with immunosuppressive therapy: horse anti-thymocyte globulin 40 mg/kg/day IV for 4 days plus ciclosporin 5 mg/kg/day orally (target trough 200 to 400 micrograms/L), with eltrombopag added in selected protocols. Neutropenic fever is an emergency: blood cultures and empirical IV antibiotics (piperacillin-tazobactam) within 1 hour; transfuse leucodepleted, CMV-safe red cells and platelets; PJP, antifungal and antiviral prophylaxis.
d) What are the major long-term complications and what surveillance is needed? (1 mark)
Complications: infection and bleeding (early causes of death), transfusional iron overload (treat with deferasirox), alloimmunisation/platelet refractoriness, serum sickness from ATG, ciclosporin nephrotoxicity, and clonal evolution into PNH, MDS or AML (especially monosomy 7) over years — warranting lifelong haematology follow-up with blood counts and PNH flow cytometry every 6 to 12 months.