A 66-year-old woman with known mild hypertension treated with bendroflumethiazide experienced a transient ischaemic attack affecting her speech which resolved completely after about 3 hours. She had noticed occasional blurring of her vision over the past 3 months. She had not smoked for 35 years and drank eight units of alcohol weekly. Her General Practitioner commenced her on aspirin 75 mg daily. Renal and hepatic function were normal, but a blood count showed a raised haemoglobin and reduced serum erythropoietin (EPO) level (Table 23.1). The Janus kinase 2 (JAK2) gene was shown to be mutated.
What is the most likely diagnosis?
How should the blood count abnormalities be investigated?
How should her condition be managed?
Table 23.1Summary of patient's investigation results |Favorite Table|Download (.pdf) Table 23.1 Summary of patient's investigation results
|Parameter ||Value ||Units ||Reference range |
|Haemoglobin ||19.4 ||g/dl ||11.5–16.0 |
|White cell count ||7.32 ||109/l ||4.0–11.0 |
|Platelets ||765 ||109/l ||150–400 |
|Packed cell volume ||0.60 || ||0.37–0.47 |
|Red cell count ||7.76 ||1012/l ||3.80–5.80 |
|Mean cell volume ||74 ||fl ||78–100 |
|Mean corpuscular haemoglobin ||25.0 ||pg ||27.0–32.0 |
|Neutrophil count ||4.52 ||109/l ||2.00–7.50 |
|Lymphocyte count ||1.33 ||109/l ||1.00–4.50 |
|Monocyte count ||0.43 ||109/l ||0.20–0.80 |
|Eosinophil count ||0.50 ||109/l ||0.04–0.40 |
|Basophil count ||0.30 ||109/l ||<0.10 |
|Serum erythropoietin ||1.0 ||mIU/ml ||3.0–18.0 |
|AK2 ||Mutated || || |
The three classical chronic myeloproliferative disorders (excluding Philadelphia-positive chronic myeloid leukaemia) – polycythaemia vera (PV), idiopathic myelofibrosis (IMF) and essential thrombocythaemia (ET) – are clonal disorders with an initiating event in a pluripotent stem cell. A small proportion will transform to an acute myeloid leukaemia.
Polycythaemia vera presents most commonly with vascular events of all types, as an incidental finding on routine blood counts and occasionally as gout. A special case of vascular event is the Budd–Chiari syndrome. Historically, the diagnosis depended on a ‘points’ system of major and minor criteria.1 The major criteria were demonstration of a raised red cell volume (to distinguish true from apparent erythrocytosis), absence of a secondary cause, palpable splenomegaly and a clonality marker, e.g. cytogenetic abnormalities in the marrow. The minor criteria were neutrophilia, thrombocytosis, radiological splenomegaly, demonstration of EPO-independent erythroid colony growth and a low EPO level. Typical bone marrow morphology is shown in Figure 23.1. Polycythaemia vera has a median age of onset of 60 years with no gender distinction. The outlook for untreated PV is dismal, with a median survival of 18–24 months, the majority of deaths being due to vaso-occlusive events. The aim of treatment is to prevent vascular events and minimize transformations to acute leukaemia, a terminal event which has clearly been shown to be increased by alkylating agents and radioactive phosphorus treatment. Polycythaemia vera may also transform to myelofibrosis.
Marrow trephine biopsy showing ...