Is a clonal disorder involving a

multipotent hematopoietic progenitor

cell in which phenotypically normal red
cells, granulocytes and platelets
accumulate in the absence of
recognizable physiologic stimulus
Most common of the chronic
myelopoliferative disorders
Occurs in 2 per 100,000 persons

Unknown
Chromosome abnormalities 20q and
trisomy 8 and 9 documented in 30% of
untreated PV patients
Mutation in the autoinhibitory,
pseudokinase domain of the tyrosine
kinase JAK2

Replaces valine with phenylalanine (V617F)

causing activation of kinase

Janus Kinase 2 (JAK2) has tyrosine kinase

activity and is involved in signal transduction
from EPOR (erythropoietin receptor) to nucleus
gene expression nucleus for gene expression

Single nucleotide JAK2 mutation (JAK2

V617F)

Valine to phenylalanine substition at codon 617

Mutation occurs in pseudokinase (normally

negative regulator of kinase activity)
domain of JAK2 gene resulting in
constitutively activated tyrosine kinase
Exclusive to disorders of myeloid lineage
and not observed in lymphoid neoplasms or
solid tumors

Median age of diagnosis is 60 but

seen in wide age range between
20 and 85
Slightly higher incidence in men
than women (2.8 vs. 1.3
cases/100,000 per year,
respectively)

PVSG (Polycythemia Vera Study

Group)
BCSH (British Committee for
Standards in Haematology)
WHO (World Health Organization)

Criteria PVSG (Polycythemia Vera Study

Group)
MAJOR

1. Raised red cell mass (RCM), male > 36 ml/kg, female > 32 ml/kg
2. Normal arterial oxygen saturation > 92%
3. Splenomegaly

MINOR

B1 Platelet count > 400 x 109/l

B2 White blood cell count (WBC) > 12 x 109/l
B3 Leucocyte alkaline phosphatase > 100
B4 Serum B12 > 900 pg/ml or unbound B12 binding capacity > 220
pg/ml

Diagnosis

3 major establishes PV
Major 1 and 2 + two of minor criteria establishes PV

MAJOR

1
2
3
4

MINOR

1 Platelet count > 400 x 109/l

2 Neutrophil count > 10 x 109/l
3 Splenomegaly on ultrasound scanning
4 Low serum EPO or characteristic burst forming units - erythroid
(BFU-E) growth

Diagnosis
Major 1 + 2 + 3 or 4 establishes PV
2 major (1+2) + two of minor establishes PV

Raised RCM or hematocrit (HCT) > 0.60 (males), > 0.56 (females)
No secondary erythrocytosis
Palpable spleen
Abnormal karyotype

MAJOR

1 Raised RCM or haemoglobin (Hb) > 18.5 (males), > 16.5 (females)
2 No secondary erythrocytosis
3 Splenomegaly
4 Abnormal karyotype (other than Ph chromosome or BCR/ABL fusion gene in
marrow cells)
5 Endogenous erythroid colony (EEC) formation

MINOR
1 Platelet count > 400 x 109/l
2 WBC > 12 x 109/l
3 Bone marrow biopsy (BMB) showing panmyelosis with erythroid and
megakaryocytic proliferation
4 Low serum erythropoietin (EPO)

Diagnosis

Major 1 + 2 and any other major category establishes PV

Major 1 + 2 + two of minor category establishes PV

First recognized by the incidental

discovery of a high hemoglobin or
hematocrit
Splenomegaly may be initial presenting
sign
Uncontrolled erytthrocytosis causes
hyperviscosity leading to:

Symptoms of vertigo, tinnitus, headache,

visual disturbances and TIAs

Systolic Hypertension
Venous or arterial thrombosis

Cerebral, cardiac and mesenteric are most

commonly involved
Digital ischemia
Acid peptic disease
GI bleeding
Intraabdominal venous thrombosis

erythromelalgia

Splenomegaly
Facial plethora (ruddy cyanosis)
Hepatomegaly
Injection of conjunctival small vessels
Excoriation of skin suggesting severe
pruritus
Stigmata of prior arterial or venous
thrombotic event
Gouty arthritis
Erythromelalgia

Pruritus

Especially following vigorous rubbing of

skin after warm bath or shower
Suggested that mast cell degranulation
and release of histamine play a role
Also release of adenosine diphosphate
from red cells or catecholamines from
adrenergic vasoconstrictor nerves when
skin is cooled may cause plt aggregation
and local production of pruritogenic
factors

Erythromelalgia

Burning pain in feet or hands

accompanied by erythema, pallor, or
cyanosis in presence of palpable pulses
Microvascular thrombotic complication in
PCV and ET

Thrombosis

Secondary to increases in blood viscosity

and platelet number
15% of PCV pts with a prior major
thrombotic complication (ie CVA, MI,
thrombophlebitis, DVT, PE)
De novo presentation of thrombosis in pts
with Budd-Chiari syndrome and portal,
splenic, or mesenteric vein thrombosis
Suspect PCV in pts with these diagnosis
under age of 45.

77 patient enrolled in the study

4 year study
Thrombotic complication occurred in
32.69% of the population

ACS (24%)
Mesenteric artery thrombosis (20%)
Portal Vein Thrombosis (4%)
Hepatic Vein thrombosis (4%)
Erythromelalgia (4%)
Thrombotic Complications Assessment in polycythemia
bahrain Medical Bulletin Vol 31 No. @ June 2009

Thrombosis (29%)
Hematologic malignancies (ie AML
or MDS, 23%)

Rate of hematologic transformation ~1.3

episodes per 100 patient years

Non-hematologic malignancies
(16%)
Hemorrhage (7%)
Myeloid metaplasia with
myelofibrosis (3%)

Goals of therapy
Prevent thrombosis

Maintain Hgb < 140 g/l, Hct <45%

in men
Hgb < 120 g/l, Hct <42%
in
women

Phlebotomy

The mainstay of treatment, which is aimed at

reducing hyperviscosity by decreasing the venous
hematocrit level to less than 45 percent (0.45) in
white men and 42 percent (0.42) in blacks and
women.
The PVSG reported the best median survival, 12.6
years, for this kind of treatment.

Berk PD, Wasserman LR, Fruchtman SM, Goldberg JD. Treatment of

polycythemia vera: a summary of clinical trials conducted by the
polycythemia vera study group. In: Wasserman LR, Berk PD, Berlin NI,
eds. Polycythemia vera and the myeloproliferative disorders.
Philadelphia: W.B. Saunders, 1995:16694.

Only indicated when a thrombosis has

occurred and can be difficult to monitor
owing to the artifactual imbalance
between the test tube anticoaulant and
plasma,

Hydroxyurea

Acts by non-alkalating mechanism to

inhibit the enzyme ribonucleotide
diphosphate reductase involved in DNA
synthesis
Reduced incidence of thrombosis
compared to phlebotomy
Effective in reducing blood counts
although transient cytopenia may occur
Some question of whether this drug has
potential for being leukemogenic,
although not proven

Interferon alpha

Wide range of biological actions including antiproliferative and cellular differentiating effects
Shown to provide relief from intractable
pruritus and reduce spleen size
Associated with significant side effects
including influenza-like syndrome, pyrexia,
myalgias, and athralgias
Not shown to be teratogenic or cross placenta
thus could be used in pregnancy

Imatinib (Gleevec)

Tyrosine kinase inhibitor which inhibits

tyrosine kinase activity of BCR-ABL
(remember CML)
In vitro it inhibits autonomous growth of
erythroid colonies in PCV
Could this have similar effect on tyrosine
kinase activity of JAK2?