Page 224 - Essential Haematology

210 / Chapter 15 Myeloproliferative neoplasms

during pregnancy. A long - acting Pegylated prepara-

Table 15.5 Causes of a raised platelet count.
tion is preferred. JAK2 inhibitors are now being
introduced into clinical trials.
Reactive
Haemorrhage, trauma, postoperative
Chronic iron defi ciency Course
Malignancy
Chronic infections Often the disease is stationary for 10 – 20 years or

Connective tissue diseases (e.g. rheumatoid more. The disease may transform after a number of

arthritis) years to myelofibrosis but the risk of transformation
Post - splenectomy to acute leukaemia is relatively low ( < 5%).
Endogenous
Essential thrombocythaemia ( JAK2 mutation + Primary m yelofi brosis
or − )
The predominant feature of primary myelofi brosis

Some cases of polycythaemia vera, primary

myelofi brosis, BCR - ABL1 + chronic myeloid is a progressive generalized reactive fibrosis of the
leukaemia, myelodysplasia (5q - or refractory bone marrow in association with the development
anaemia with ring sideroblasts) of haemopoiesis in the spleen and liver (known as
myeloid metaplasia). Clinically this leads to anaemia
and massive splenomegaly. In some patients there is

osteosclerosis. Myelofibrosis is a clonal stem cell
The patients most at risk of thrombosis are those disease. Th e fibrosis of the bone marrow is second-

over 60 years old or with previous thrombotic epi- ary to hyperplasia of abnormal megakaryocytes. It
sodes. Additional risk factors include presence of is thought that fibroblasts are stimulated by platelet -

JAK2 mutation, smoking history and hypertension; derived growth factor and other cytokines secreted
the importance of the absolute platelet count is by megakaryocytes and platelets.
uncertain. Th e JAK2 mutation occurs in approximately
Standard cardiovascular risk factors such as cho- 50% of patients, whereas around 15% have a muta-
lesterol, smoking, diabetes, obesity and hyperten- tion of TET - 2 and some patients carry mutations
sion should be identified and treated. Low dose in the MPL gene (the receptor for thrombopoietin).

aspirin at 75 mg/day is generally recommended in Non - specific cytogenetic abnormalities may be

all cases. found in approximately half of patients. One - third
Patients at high risk include those over 60 years of patients with similar features have a previous
of age, with previous thrombosis or with platelet history of PV or ET and some patients present
9
count over 1500 × 10 /L and this group should with clinical and laboratory features of both
be treated with drugs to reduce the platelet count. disorders.
Low risk patients are those aged < 40 years and
here aspirin alone is suffi cient. Optimum control
Clinical f eatures
of the medium risk group (age 40 – 60 years) is
uncertain. 1 An insidious onset in older people is usual with

Hydroxyurea is the most widely used treatment symptoms of anaemia.
and is well tolerated although some patients develop 2 Symptoms resulting from massive splenomegaly
skin ulceration or pigmentation. Anagrelide is a (e.g. abdominal discomfort, pain or indigestion)
good second - line treatment but has more side - are frequent; splenomegaly is the main physical
effects, particularly on the cardiovascular system, finding (Fig. 15.4 b).

and a possible increased risk of myelofi brosis is also 3 Hypermetabolic symptoms such as loss of weight,

of concern. These two drugs can be combined at anorexia, fever and night sweats are common.
low doses to reduce side - eff ects. α - Interferon is also 4 Bleeding problems, bone pain or gout occur in a
effective and is often used in younger patients or minority of patients.