A 32-year-old man presented with a two-month history of increasing tiredness and shortness of breath. His exercise tolerance reduced over the two-month period from regularly running eight kilometres to only being able to walk. Over the last week he had recurrent nose bleeds and spontaneous bruising. At the time of his presentation he had had no raised temperatures. Two months prior to his presentation he had a diarrhoeal illness after travelling to India and received treatment with metronidazole for presumed giardiasis. There was no other relevant previous or family history. His three sisters and brother were all alive and well. He was on no drugs. On examination he had some bruising, a petechial rash and two small fundal haemorrhages. There was no lymphadenopathy or hepatosplenomegaly. At presentation his white cell count was 1.3 × 109/l, neutrophils 0.6 × 109/l, haemoglobin 5.1 g/dl and platelets 6 × 109/l. A blood film was consistent with pancytopenia and had no diagnostic features.
What are the most likely causes of his pancytopenia?
What investigations would you perform?
What treatment would you give over the next 24 hours?
The differential diagnosis includes bone marrow replacement by leukaemia (acute myeloid leukaemia or acute lymphoblastic leukaemia – the lack of blasts in the blood film is unusual but is observed in rare cases, for example in acute promyelocytic leukaemia) or aplastic anaemia (usually idiopathic or secondary to drugs, hepatitis, etc.).1 Aplastic anaemia is most likely in view of the prior history of illness treated with antibiotics (although metronidazole is not a very well-recognized cause of aplastic anaemia, this side-effect has been reported), the lack of abnormalities on the blood film and the profound anaemia with relatively few signs (suggesting a slow onset). Other unlikely causes would be pernicious anaemia (unlikely due to the patient’s age and gender), myelodysplastic syndrome (more common in the elderly and a morphologically abnormal blood film would be expected) and metastatic carcinoma (expectation of a leuco-erythroblastic blood film).
The diagnosis of aplastic anaemia was established with a bone marrow aspirate and trephine biopsy (Figure 8.1). There was no increase in blasts in the marrow and cytogenetic analysis revealed a normal male karyotype (46, XY). Flow cytometry revealed the normal expression of glycosyl phosphatidyl inositol-linked antigens, excluding a diagnosis of paroxysmal nocturnal haemoglobinuria (PNH).2 He has severe aplastic anaemia according to the Camitta criteria.3 His initial management included the transfusion of platelets to maintain a level over 50 × 109/l in view of his fundal haemorrhages (a finding that indicates a potential risk of intracranial haemorrhage and necessitates intensive correction of the haemostatic defect – in this case thrombocytopenia). He was transfused with six units of packed red blood cells. The patient and all his siblings were tissue typed – the brother was human leukocyte antigen (HLA)-identical with the ...