Page 222 - Essential Haematology

208 / Chapter 15 Myeloproliferative neoplasms

JAK 2 i nhibitors Apparent p olycythaemia

Drugs which inhibit JAK2 activity are in clinical Apparent polycythaemia, also known as pseudopoly-
trials and are showing great promise, in both JAK2 cythaemia, is the result of plasma volume contrac-
wild type and mutated cases. It is anticipated that tion. By definition, the red cell mass is normal. Th e

they may become first - line agents. cause is uncertain but it is far more common than
PV. It occurs particularly in young or middle - aged
Course and p rognosis men and may be associated with cardiovascular
problems, e.g. hypertension (Gaisb ö ck ’ s syndrome),
Typically, the prognosis is good with a median sur-
vival of 10 – 16 years. Thrombosis and haemorrhage myocardial ischaemia or cerebral transient ischae-

are the major clinical problems. Increased viscosity, mic attacks. Diuretic therapy, heavy smoking,
vascular stasis and high platelet levels may all con- obesity and alcohol consumption are frequent asso-
tribute to thrombosis, whereas defective platelet ciations. Venesection to maintain a haematocrit
function may promote haemorrhage. around 0.45 – 0.47 is recommended in those with a

Transition from PV to myelofibrosis occurs in recent history of thrombosis, or with additional risk
approximately 30% of patients and approximately factors for this.
32
5% of patients progress to acute leukaemia. P and
busulfan are generally avoided, particularly in Differential d iagnosis of
younger subjects as they may increase this risk. p olycythaemia

Th e identification of the JAK2 mutation has ration-

Congenital c auses
alized the approach to diagnosis of polycythaemia.
Congenital causes are relatively rare and include A three - stage approach to diagnosis has been
cases caused by mutations in the genes that regulate suggested:
oxygen sensing ( VHL , PHD2 or HIF2A ) (see
1 Stage 1 History and examination

Chapter 2 ) as well as mutation of the erythropoietin
Full blood count/fi lm
receptor and haemoglobin mutations that lead to
JAK2 mutation

high oxygen affinity variants with subsequent tissue

Serum ferritin
hypoxia. These patients often have a family history

Renal and liver function tests
of polycythaemia and present at a young age.
If JAK2 is negative and there is no clear secondary
Secondary p olycythaemia cause, proceed to stage 2.
2 Stage 2 Red cell mass

The causes of secondary polycythaemia are listed in Arterial oxygen saturation
Table 15.3 . Abdominal ultrasound
Acquired causes are due to an increase in the Serum erythropoietin level
erythropoietin level. Hypoxia caused by chronic Bone marrow aspirate and trephine
obstructive airways disease is one of the most fre- Cytogenetic analysis
quent, and measurement of arterial oxygen satura- BFU E culture
tion is a valuable test. Renal and tumour causes of Specialized tests may then be required.
inappropriate erythropoietin secretion are rare. 3 Stage 3 Arterial oxygen dissociation
There is very little evidence on which to guide Sleep study

a treatment plan. Some would advise venesection if Lung function studies
the haematocrit is above 0.54 with the aim of reduc- Gene mutations EPOR, VHL, PHD2
ing to a target around 0.5. A lower target for vene-
section may be used if there is hypertension, Essential t hrombocythaemia
diabetes, dyspnoea, angina or a previous thrombotic
episode. Low dose aspirin may be of benefi t for In this condition there is a sustained increase in
many patients. platelet count, because of megakaryocyte prolifera-