harrison topic

2.  Increase in Hb above normal.
 Can be real or
apparent due to decrease in
plasma volume [ spurious or relative
polycythemia or Gaisböck's syndrome ]

3.  Erythrocytosis:
documentation of increased red cell
mass
 Polycythemia:
any increase in red cells

4.  Abnormally high Hb >17g/dl in males and
>15 g/dl in females
 Haematocrit >50 percent in males and
>45 percent in females.

5.  To differentiate from spurious or relative
eruthrocytosis,
 Measure red cell mass
 If < 36ml/kg in men or < 32ml/kg in
females, it is spurious or relative
polycythemia.

6.  POLYCYTHEMIA can be
 Primary : polycythemia vera
associated with low
erythropoetin levels
 Secondary : associated with high
erythropoetin levels

7.  A normal erythropoietin level, however,
does not exclude a secondary cause for
erythrocytosis or PV.

8.  Tissue hypoxia:
 lung or heart disease
 AV or intracardiac shunt
 high altitude
 CO poisoning
 high affinity haemoglobinopathy

9.  Abnormal overproduction of erythropoetin
 renal cysts
 renal artery stenosis
 tumors with ectopic EPO production

10.  Familial form of polycythemia
 Rare
 Associated with normal erythropoetin
levels but hyperresponsive EPO receptors
due to mutations.
 VHL mutations ( chuvash polycythemia )

11.  Differentiate whether due to tissue
hypoxia or autonomous EPO production
 Measure arterial O2 saturation
 If low saturation (< 92 percent)
living at high altitude
if not,
evaluate for heart or lung disease

12.  Smokers :
elevated EPO levels due to displacement
of O2 by CO.
Smoker’s polycythemia [ high HbCO
levels]
 Incresed O2 affinity haemoglobinopathy.

13.  EPO producing neoplasms:
Hepatoma
uterine leiomyoma
renal cancer or cysts
cerebellar haemangiomas
adrenal tumors
phaeochromocytoma
meningioma

14.  Drugs causing polycythemia:
Androgens
recombinant erythropoietin

15.  h/o smoking
 Living at high altitude
 h/o congenital heart disese, sleep apnea,
chronic lung disease

16.  Related to hyperviscosity and
thrombosis
 Digital ischaemia
 Budd chiari syndrome with hepatic vein
thrombosis
 Abdominal vessel thromboses

17.  Neurological symptoms:
vertigo
tinnitus
headache
visual disturbances
 Hypertension

18.  Aquagenic pruritus and symptoms related
to hepatosplenomegaly in patients with
polycythemia vera
 Easy bruising
 Epistaxis
 Bleeding from GIT
 Peptic ulcer disese

19.  Symptoms of hypoxemia
cyanosis on exertion
headache
impaired mental acuity
fatigue

20.  Ruddy complexion
 Splenomegaly ( favours polycythemia vera )
 Cyanosis or evidence of right to left shunt
suggests congenital heart disease
 Pulmonary artery hypertension d/t increased
blood viscosity
 Raised pulmonary vascular resistance d/t
hypoxemia
 Cor pulmonale

22.  PV is a clonal disorder involving a
multipotent hematopoietic progenitor cell
in which phenotypically normal red cells,
granulocytes, and platelets accumulate in
the absence of a recognizable physiologic
stimulus.

23.  The etiology of PV is unknown.
 Nonrandom chromosome abnormalities
such as 20q and trisomy 8 and 9 have
been documented in up to 30% of
untreated PV patients

24.  mutation in the autoinhibitory,
pseudokinase domain of the tyrosine
kinase JAK2—that replaces valine with
phenylalanine (V617F), causing
constitutive activation of the kinase—
appears to have a central role in the
pathogenesis of PV.

25.  JAK2 gene is located on the short arm of
chromosome 9, and loss of heterozygosity on
chromosome 9p, due to mitotic
recombination is the most common
cytogenetic abnormality in PV.
 loss of heterozygosity in this region leads to
homozygosity for the mutant JAK2 V617F.
 More than 90% of PV patients express this
mutation

26.  splenomegaly may be the initial
presenting sign in PV,
 the incidental discovery of a high
hemoglobin or hematocrit.
 aquagenic pruritus,
 no symptoms distinguish PV from other
causes of erythrocytosis.

27.  Erythema, burning, and pain in the
extremities, a symptom complex known as
erythromelalgia, is another complication of
the thrombocytosis of PV due to increased
platelet stickiness

28.  Given the large turnover of hematopoietic
cells, hyperuricemia with secondary gout,
uric acid stones, and symptoms due to
hypermetabolism can also complicate the
disorder.

29.  When PV presents with erythrocytosis in
combination with leukocytosis,
thrombocytosis, or both, the diagnosis is
apparent.
 However, when patients present with an
elevated hemoglobin or hematocrit alone, or
with thrombocytosis alone, the diagnostic
evaluation is more complex

30.  Assay for JAK2 V617F has superseded
other tests for establishing the diagnosis of
PV.

31.  Only three situations cause microcytic
erythrocytosis: -thalassemia trait, hypoxic
erythrocytosis, and PV.
 With -thalassemia trait the RDW is normal,
 whereas with hypoxic erythrocytosis and PV,
the RDW is usually elevated due to iron
deficiency

32.  Thrombosis due to erythrocytosis is the most
significant complication, and maintenance of
the hemoglobin level at 140 g/L (14 g/dL;
hematocrit <45%) in men and 120 g/L (12
g/dL; hematocrit <42%) in women is
mandatory to avoid thrombotic
complications.
 Phlebotomy serves initially to reduce
hyperviscosity by bringing the red cell mass
into the normal range.

33.  Periodic phlebotomies serve to maintain the
red cell mass within the normal range and to
induce a state of iron deficiency that
prevents an accelerated reexpansion of the
red cell mass.
 In most PV patients, once an iron-deficient
state is achieved, phlebotomy is usually only
required at 3-month intervals.

34.  Anticoagulants are only indicated when a
thrombosis has occurred
 Asymptomatic hyperuricemia (<10 mg%)
requires no therapy,
allopurinol should be administered to avoid
further elevation of the uric acid when
chemotherapy is employed to reduce
splenomegaly or leukocytosis or to treat
pruritus

35.  Generalized pruritus intractable to
antihistamines or antidepressants such as
doxepin
 interferon (IFN-)
 psoralens with ultraviolet light in the A
range (PUVA) therapy
 hydroxyurea

36.  Asymptomatic thrombocytosis requires no
therapy unless the platelet count is
sufficiently high to cause an acquired form
of von Willebrand's disease
 Symptomatic splenomegaly can be treated
with IFN-

37.  Pegylated IFN- produces complete remissions
in PV patients.
 Anagrelide, a phosphodiesterase inhibitor,
can reduce the platelet count and, if
tolerated, is preferable to hydroxyurea
because it lacks marrow toxicity and is
protective against venous thrombosis.

38.  Alkylating agents and radioactive sodium
phosphate (32P) are leukemogenic in PV, and
their use should be avoided.
 hydroxyurea is the preferred cytotoxic
agent, but it does not prevent either
thrombosis or myelofibrosis in this disorder,
is itself leukemogenic, and should only be
used for a short time

39.  In some patients., massive splenomegaly
unresponsive to reduction by therapy and
associated with intractable weight loss will
require splenectomy.
 Allogeneic bone marrow transplantation
may be curative in young patients.

40.  Most patients with PV can live long lives
without functional impairment when their
red cell mass is effectively managed with
phlebotomy alone.
 Chemotherapy is never indicated to control
the red cell mass unless venous access is
inadequate.

41. THANK YOU