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Fifth stage
Medicine
Lec-7
د.خالد نافع
21/2/2016
Polycythaemia vera
Definition of polycythemia:
Raised packed cell volume (PCV / HCT)
Male > 0.52 (52%)
Female > 0.48 (48%)
Classification of polycythemia in general:
Absolute ;if male with HCT ≥0.60,female≥0.56
o Primary proliferative polycythaemia (polycythaemia vera)
o Secondary polycythaemia
o Idiopathic erythrocytosis
Apparent
o Plasma volume or red cell mass changes
o The presence of hypertension, smoking, excess alcohol consumption and/or
diuretic use is consistent with low volume polycythaemia (Gaisbock’s syndrome)
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Clinical features:
Age > 40 year
o May occur in young adults and rare in childhood
o symptoms of hyperviscosity, such as lassitude, loss of concentration, headaches,
dizziness, blackouts, pruritus and epistaxis
Majority patients present due to vascular complications
o Thrombosis (including portal and splenic vein)
o DVT
o Hypertension
o poor vision
o Skin complications ( aquagenic pruritus, erythromelalgia)
o Haemorrhage (GIT) due to platelet defect
Hepatosplenomegaly
Erythromelalgia
o Increased skin temp
o Burning sensation
o Redness
Investigation:
Mutation in a kinase, JAK-2 V617F, is found in over 90% of cases .
If JAK-2 mutation is negative , measurement of red cell mass.
Laboratory features and morphology:
Hb, PCV (HCT), and Red cell mass increased
Increased neutrophils and platelets
Plasma urate high
Hypercellular bone marrow
Low serum erythropoietin
TREATMENT:
Aspirin reduces the risk of thrombosis.
Venesection gives prompt relief of hyperviscosity symptoms. Between 400 and
500 mL of blood (less if the patient is elderly) are removed and the venesection is
repeated every 5–7 days until the haematocrit is reduced to below 45%.
Suppression of marrow proliferation with hydroxycarbamide or interferon alfa may
reduce the risk of vascular occlusion, control spleen size and reduce transformation
to myelofibrosis
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Secondary polycythaemia
Polycythaemia due to known causes
Compensatory increased in EPO
o High altitude
o Pulmonary diseases
o Heart dzs eg- cyanotic heart disease
o Abnormal hemoglobin- High affinity Hb
o Heavy cigarette smoker
Inappropriate EPO production
o Renal disease-carcinoma, hydronephrosis
o Tumors-fibromyoma and liver carcinoma
Investigation:
Arterial blood gas
Hb electrophoresis
Oxygen dissociation curve
EPO level
Ultrasound abdomen
Chest X ray
Total red cell volume(51Cr)
Total plasma volume(125 I-albumin)
Myelofibrosis
Chronic idiopathic myelofibrosis
Progressive fibrosis of the marrow & increase connective tissue element
Agnogenic myeloid metaplasia
o Extramedullary erythropoiesis
Spleen
Liver
Abnormal megakaryocytes
o Platelet derived growth factor (PDGF)
o Platelet factor 4 (PF-4)
Insidious onset in older people
Splenomegaly- massive
Hypermetabolic symptoms
o Loss of weight, fever and night sweats
Bone pain
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Gout
Anaemia
High WBC at presentation
Later leucopenia and thrombocytopenia
Leucoerythroblastic blood film
Tear drops red cells
Bone marrow aspiration- Failed due to fibrosis
Trephine biopsy- fibrotic hypercellular marrow
The presence of a JAK-2 mutation supports the diagnosis.
Myelofibrosis-Treatment
Red cell transfusions for anaemia.
Folic acid should be given to prevent deficiency.
Cytotoxic therapy with hydroxycarbamide may help control spleen size, the white
cell count or systemic symptoms.
Splenectomy may be required for a grossly enlarged spleen or symptomatic
pancytopenia secondary to splenic pooling of cells and hypersplenism.
HSCT may be considered for younger patients.
Ruxolitinib, an inhibitor of JAK-2.
Essential thrombocythaemia(ET)
Primary thrombocytosis / idiopathic thrombocytosis
Clonal myeloproliferative disease of megakaryocytic lineage
o Sustained thrombocytosis
o Increase megakaryocytes
o Thrombotic or/and haemorrhage episodes
Positive criteria
o Platelet count >600 x 109/L
o Bone marrow biopsy; large and increased megas.
o The presence of a JAK-2 mutation supports the diagnosis but is not universal.
Criteria of exclusion
o No evidence of Polycythaemia vera
o No evidence of CML
o No evidence of myelofibrosis (CIMF)
o No evidence of myelodysplastic syndrome
o No evidence of reactive thrombocytosis
Bleeding
Trauma
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Post operation
Chronic iron def
Malignancy
Chronic infection
Connective tissue disorders
Post splenectomy
Clinical features
Haemorrhage
Microvascular occlusion
TIA, gangrene
Splenic or hepatic vein thrombosis
Hepatosplenomegaly
Treatment
Low dose aspirin to reduce the risk of occlusive vascular events.
Low risk patients (age < 40 years, platelet count < 1000 × 109/L and no bleeding or
thrombosis) may not require treatment to reduce the platelet count.
For those with a platelet count above 1000 × 109/L, with symptoms, or with other
risk factors for thrombosis such as diabetes or hypertension, treatment to control
platelet counts should be given.
Agents include oral hydroxycarbamide or anagrelide, an inhibitor of
megakaryocyte maturation.
Intravenous radioactive phosphorus (32P) may be useful in old age.