1
Fifth stage
Medicine
Lec-
د.خالد نافع
15/11/2016
Polycythaemia rubra vera
Polycythaemia vera :
Definition of polycythemia
Raised packed cell volume (PCV / HCT)
Male > 0.52 (52%)
Female > 0.48 (48%)
Classification
Absolute ;if male with HCT ≥0.60,female≥0.56
Primary proliferative polycythaemia (polycythaemia vera)
Secondary polycythaemia
Idiopathic erythrocytosis
Apparent
Plasma volume or red cell mass changes
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
May occur in young adults and rare in childhood
symptoms of hyperviscosity, such as lassitude, loss of concentration,
headaches, dizziness, blackouts, pruritus and epistaxis
Majority patients present due to vascular complications
Thrombosis (including portal and splenic vein)
DVT
Hypertension
poor vision
Skin complications ( aquagenic pruritus, erythromelalgia)
Haemorrhage (GIT) due to platelet defect
Hepatosplenomegaly
Erythromelalgia
Increased skin temp
Burning sensation
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
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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% for male and
42% for female.
Suppression of marrow proliferation with hydroxycarbamide or interferon alfa may
reduce the risk of vascular occlusion, control spleen size and reduce transformation
to myelofibrosis
Secondary polycythaemia :
Polycythaemia due to known causes
Compensatory increased in EPO
High altitude
Pulmonary diseases
Heart dzs eg- cyanotic heart disease
Abnormal hemoglobin- High affinity Hb
Heavy cigarette smoker
Inappropriate EPO production
Renal disease-carcinoma, hydronephrosis
Tumors-fibromyoma and liver carcinoma
Investigation :
1. Arterial blood gas
2. Hb electrophoresis
3. Oxygen dissociation curve
4. EPO level
5. Ultrasound abdomen
6. Chest X ray
7. Total red cell volume(51Cr)
8. Total plasma volume(125 I-albumin)
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Myelofibrosis :
Chronic idiopathic myelofibrosis
Progressive fibrosis of the marrow & increase connective tissue element
Agnogenic myeloid metaplasia
Extramedullary erythropoiesis
Spleen
Liver
Abnormal megakaryocytes
Platelet derived growth factor (PDGF)
Platelet factor 4 (PF-4)
Myelofibrosis-Cont. :
Insidious onset in older people
Splenomegaly- massive
Hypermetabolic symptoms
Loss of weight, fever and night sweats
Bone pain
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.
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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
Sustained thrombocytosis
Increase megakaryocytes
Thrombotic or/and haemorrhage episodes
Positive criteria
Platelet count >600 x 10
9
/L
Bone marrow biopsy; large and increased megakaryocytes.
The presence of a JAK-2 mutation supports the diagnosis but is not universal.
Criteria of exclusion
No evidence of Polycythaemia vera
No evidence of CML
No evidence of myelofibrosis (CIMF)
No evidence of myelodysplastic syndrome
No evidence of reactive thrombocytosis
Bleeding
Trauma
Post operation
Chronic iron deficiency
Malignancy
Chronic infection
Connective tissue disorders
Post splenectomy
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Essential thrombocythaemia(ET) :
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.