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Perth Haematology :: Dr Steven Ward

Polycythaemia Rubra Vera (PRV)

 

 

Polycythaemia = too much red blood (increased red blood cell mass)

 

This may be:

bulletPrimary : PRV - due to increased marrow red cell production
bulletSecondary: ie an appropriate or stimulated
bulletincreased red cell mass due to hypoxia (lack of oxygen) - in lung or heart disease
bulletdue to liver, brain or kidney disorders
bulletRelative: due to reduced plasma volume and normal red cell mass
bulletApparent: high Haematocrit but normal red cell mass

 

 Polycythaemia leads to:

bullet

Increased Hb, Red Cell Count (RCC) and Haematocrit (Hct) [Hct is also known as Packed Cell Volume (PCV)]

bullet

Increased blood viscosity

bullet

Features of the causative disorder (lung or heart usually)

bullet

Primary PRV also causes a rise in the white cells and platelets, enlarged spleen and high blood uric acid levels (and potentially gout)

bullet

Untreated polycythaemia can lead to thrombosis - stroke or myocardial infarction; hypertension; bleeding.

 

Diagnosis:

The best way to diagnose polycythaemia is by a Red Cell Mass (RCM) study. This involves the drawing of a measured amount of patient blood, labelling that blood with a known amount of a mild radioactive tracer which bins the red cells, and a second tracer to bind a plasma component (usually albumin). The patient blood with tracers is then reinjected to the patient and allowed to mix and circulate with the rest of the blood. After a time a second blood sample is taken and the radioactivity in this sample is measured. The red cell mass, blood volume and plasma volume can then be calculated.

 

Normal values:

                                MALE    FEMALE

Red Cell Mass        25-35      22-30        mL/kg body wt

Plasma Volume      28-38      31-38        mL/kg

Blood Volume         52-70      54-64        mL/kg

 

Mean Predicated RCM = 0.47 x 0.91 x BV for males       Values > 25% above this = polycythaemia

                                            0.43 x 0.91 x BV for females    Values > 35% above this = polycythaemia

 

    OR      Males: (1486 x SA)-825 mL

                Females: (1.06 x Age) + (822 x SA) mL                SA = Surface Area

 

Additional Tests to find the Cause of Absolute polycythaemia

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Arterial Blood Gases - to measure oxygen and CO2 levels in the blood.

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Chest x-ray - to look for lung / heart disease

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Ultrasound of abdomen - to look for liver or kidney causes

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Hb electrophoresis - to look for a high-affinity Hb variant (inherited disorder of Hb with high-affinity for oxygen, so doesn't give oxygen up to tissues easily)

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Bone marrow studies - to exclude other primary MPD

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Marrow cytogenetics and molecular markers - BCR-ABL and JAK2

 

Diagnostic Criteria for PRV [BCSH]

    Major:    A1: Increased RCM  >25% above predicted mean or HCt  M > 0.6  F >0.56

                    A2: No cuase for 2y erythrocytosis

                    A3: Palpable splenomegaly

                    A4: Clonality marker

    Minor:    B1: Thrombocytosis (>400)

                    B2: Neutrophilia (>10; or >12.5 in smokers)

                    B3: Splenomegaly on USS

                    B4: Reduced serum EPO level

 

    A1 + A2 + (A3 or A4) = PRV

    A1 + A2 + any  2 B = PRV

 

Revised WHO Diagnostic Criteria for PRV

Diagnosis requires both major criteria and 1 minor criterion or 1st major plus 2 minor criteria.

 

Major Criteria:

1.      Hb > 185 g/L in men, 165 g/L in women, or other evidence of raised red cell volume [Hb or Hct > 99th percentile; Hb >170 M, 150 F  with documented and sustained increase of >20g/L from individualís baseline; RCM > 25% above mean normal predicated value]

2.      JAK2617V>F or other functionally similar mutations eg JAK2 exon 12 mutation

 

Minor Criteria:

1.      BM biopsy showing hypercellularity for age with panmyelosis with prominent erythroid, granulocytic and megakaryocytic proliferation

2.      Serum EPO below the reference range

3.      Endogenous erythroid colony formation in vitro

 

 

Treatment

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The aim is to reduce the Hct to <0.45 to prevent hyperviscosity (and subsequent hypertension, artherosclerosis, heart disease) and prevent thrombosis and bleeding.

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Aspirin 75mg/day has been shown to be effective at reducing thrombosis

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Venesection (blood letting): safest therapy - maintain Hct <0.45

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Hydroxyurea : reduces HCt, thrombois and bleeding. Recent studies show no increase in leukaemia or fibrosis risk above that for the disease itself.

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Other drugs: interferon, 32P (radioactive phosphorus) are occasionally used

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Itch can be  problem: often relieved by treatment of the PRV itself; other possible treatments are: cimetidine, PUVA, interferon, SSRIs.

 

Risk of Acute Leukaemia: 1.5%

Risk of Myrlofibrosis: 5-15%