Haematology

at a Glance

Fourth EditionAtul B. Mehta and A. Victor Hoffbrand

Case Studies

Case 4: A 64-year-old man with an elevated haemoglobin concentration

A 64-year-old man is referred for investigation of an elevated haemoglobin concentration (Hb = 189 g/L). He had been well until 4 months previously when he had developed weakness of his right arm and leg. This was confirmed by CT scan to be due to a thrombosis of the left middle cerebral artery. He had given up smoking 2 years ago. He gave a history of intermittent chest pain thought to be angina.
On examination, he is overweight (89 kg). His blood pressure is normal (130/80 mmHg). His pulse is regular and examination of chest is normal. On examination of his abdomen, it was difficult to be certain whether or not he had enlarged and palpable spleen. The area of splenic dullness appeared to be increased.
Investigations show:
Hb 189 g/L
WBC 12.3 × 109/L
Neutrophils 9.7 × 109/L (raised)
MCV 72
Platelets 634 × 109/L
Urea and electrolytes – normal
Liver function tests – normal
ECG – normal
Cardiac rhythm – normal.

  • (a) What is the differential diagnosis of the elevated haemoglobin concentration?

    Correct answer: A raised haemoglobin concentration could be the result of true polycythaemia (i.e. a genuine increase on red cell mass) or spurious polycythaemia (i.e. a relative polycythaemia resulting from the concentrating effect of a reduction in plasma volume). The latter is seen in men more commonly than women, smokers rather than non-smokers, and is associated with hypertension and diuretic therapy; it is also called ‘stress’ polycythaemia. True polycythaemia may be primary or secondary; a list of causes is given in Box 26.1. Chapter 26
    This man has an elevated WBC and elevated platelet count; his MCV is reduced, consistent with iron deficiency; there is a suggestion of splenic enlargement; there are no indications of a cause for secondary polycythaemia. All of these indicate that he is likely to have true primary polycythaemia (polycythaemia rubra vera, PRV).

  • (b) What further tests would you do to establish the cause?

    Correct answer: A serum feritin is indicated to confirm the iron deficiency. His serum uric acid should be estimated as there is an association of PRV with gout. DNA analysis of the JAK2 gene should be undertaken to test for the presence of the Val617Phe mutation which is present in >95% of patients with PRV. The urine should be tested to exclude haematuria, which could indicate the presence of a hypernephroma which could cause secondary polycythaemia. A serum erythropoietin assay can help to distinguish true polycythaemia (when it would be normal or low) from secondary polycythaemia (when it would be raised). Abdominal ultrasound should be undertaken to exclude a hypernephroma or the presence of renal cysts and to assess spleen size.

  • (c) Could his recent stroke be related?

    Correct answer: A raised red cell mass can predispose to thrombosis by reducing blood flow. Polycythaemia vera is also associated with an increase in blood platelet count. It is possible that he may have had undiagnosed polycythaemia for a number of years.

  • (d) What treatment would you recommend?

    Correct answer: Venesection should be undertaken to reduce the haematocrit to less than 0.45. He should be commenced on allopurinol if his serum uric acid level is normal (allopurinol can precipitate gout if the uric acid is already raised). Oral hydroxycarbamide is a myelosuppressive agent which is commonly used in the myeloproliferative disorders and is usually well tolerated. Low dose aspirin is required as thromboprophylaxis, in view of the previous history of stroke and the elevated platelet count.

  • (e) What is the underlying mechanism for the increased haemoglobin level?

    Correct answer: The JAK2 mutation causes autonomous activation of signal transduction from a growth factor receptor (e.g. for erythropoietin) in the absence of the growth factor. This leads to uncontrolled cell proliferation. Individuals with PRV are usually heterozygous for this acquired mutation which is only present in bone marrow derived cells; homozygous states are associated with a more severe phenotype.

  • (f) What other complications can occur?

    Correct answer: Thrombosis, gout, peptic ulceration and pruritus can all occur in PRV. About 25% of patients progress to myelofibrosis, although this usually takes many years. About 5% of patients ultimately develop acute myeloid leukaemia (AML).

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