Polycythemia

Introduction
Polycythemia- is an increase number of red blood
cells in the blood. In polycythemia the levels of
hemoglobin (Hb), Hematocrit (Hct)-is the ratio of the
volume of red cells to the volume of whole blood or
the red blood cell (RBC) count maybe elevated when
measured in the complete blood count (CBC) as
compared to normal. Hemoglobin levels > 16.5 g/dL
in women and >18.5 g/dL in men suggest
polycythemia. In terms of hematocrit, a value > 48 in
women and 52 in men is indicative of polycythemia.
Meaning: ''Polycythemia is characterized by an
increase in absolute quantity of red cells or total RBC
volume''.
In
contrast,
relative
polycythemia
(pseudoerythrocytosis) is secondary to fluid loss or
decreased
fluid
intake
resulting
in
hemoconcentration.

Normal Hematopoiesis
Production of red blood cells (erythropoiesis)
occurs in the bone marrow. Myeloid stem cells
give rise to erythrocytes, platelets,
granulocytes, eosinophils,basophils, and
monocytes. The production of each lineage is a
function of cell proliferation, differentiation and
apoptosis.
These various stages of differentiation rely on
multiple interrelated processes
Protein growth factors, known as cytokines,
stimulate proliferation of the multilineage cells.
One of the important enzymes regulating this
process is called erythropoietin (Epo). The
majority of Epo is produced and released by the
kidneys, and a smaller portionis released by the
liver.

Types
Primary polycythemias
- Polyvythemia can result from internal
problems with the production of RBC.
- It is due to factors intrinsic to red cell
precursors , including primary familial
and congenital polycythemia (PFCP),
idiopathic erythrocytosis and
polycythemia vera(PV).
Secondary polycythemia
- If polycythemia is caused due to
another underlying medical problem, it is
referred to as secondary polycythemia.

- These are caused by factors extrinsic

to red cell precursors and include a
physiologic appropriate erythropoietin
(epo) production in response to tissue
hypoxia.
Most cases of polycythemia are secondary
and are caused by another medical
condition. Primary polycythemias are
relatively rare; for example, polycythemia
vera occurs in approximately 1 to 2 adults
per 100,000 in the US. 1% to 5% of
newborns can have polycythemia
(neonatal polycythemia).

Relative Polycythemia
- relative polycythemia describes
conditions in which red cell volume is
high due to increased blood
concentration of red cells as a result of
dehydration.
Stress Polycythemia

Etiology
Polycythemia Primary Causes:
- Inherent or acquired problems with red
blood cell production lead to polycythemia.
- Two main conditions that belong to this
category are polycythemia vera (PV or
polycythemia rubra vera[PRV]) and primary
familial and congenital polycythemia (PFCP).
- Polycythemia vera is related to a genetic
mutation in the JAK2 gene, which is thought to
increase the sensitivity of bone marrow cells
to Epo, resulting in increased red blood
cellproduction. Levels of other types of blood
cells(wbc and platelets) and also often
increased in this condition.

- Primary familial and congenital polycythemia (PFCP) is

a condition related to a mutation in the EPOR gene and
causes increased production of RBC in response to Epo.
Polycythemia Secondary Cause:
- over production of RBC results from increased
sensitivity or responsiveness to Epo( often with lower
than normal levels of Epo), in secondary polycythemia ,
more red cells are produced because of high levels of
circulating Epo.
- the main reasons for higher than normal Epo are
chronic hypoxia (poor blood oxygen levels over the long
term), poor oxygen delivery due to abnormal RBC
structure, and tumors releasing inappropriately high
amounts of Epo.
- Some common conditions that can result in elevated
erythropoietin due to chronic hypoxia or poor oxygen
supply includes: COPD, emphysema, chronic bronchitis.

> pulmonary hypertension

> congestive heart failure
> obstructive sleep apnea
> kidney cancer (renal cell carcinoma)
> uterine cancer
> chronic carbon monoxide exposure can also
lead to polycythemia.Hemoglobin naturally
has a higher affinity for carbon monoxide
than for oxygen. Therefore, when carbon
monoxide molecules attach to hemoglobin,
polycythemia (increased red cell and
hemoglobin production)may occcur in order
to compensate for the poor oxygen delivery
by the existing hemoglobin molecules. A
similar scenario can also occur with CO2 in
long term cigarette.

Neonatal polycythemia is often caused by transfer of

maternal blood from the placenta or blood
transfusions. Prolonged poor oxygendelivery to the
fetus (intrauterine hypoxia) due to insufficiency of
the placenta can also lead neonatal polycythemia.
Relative Polycythemia
- in theses situations(vomiting, diarrhea,excessive
sweating) the number of RBC is normal,but because
of the fluid loss affecting the blood(plasma), red
blood cell counts may seem elevated.
Stress Polycythemia
- this is a condition that may be seen in
hardworking, anxious, middle-aged men due to low
plasma volume, although the RBC volume may be
normal.
- other names for this condition are
pseudopolycythemia, stress erythrocytosis, or
Gaisbock's disease.

Polycythemia Risk Factors

chronic hypoxia
long term cigarette smoking
familial and predisposition;
living in high altitudes;
long term exposure to carbon monoxide
(tunnel workers, car garage attendants,
residents of highly polluted cities)and
ashkenazi jewish ancestry(may have
increased frequency of polycythemia vera
due to genetic susceptibility).

Signs & Symptoms

easy bruising
easy bleeding
blood clot formation(potentially leading to
[pulmonary embolism]);
bone and joint pain in hip or rib
headache
itching
after a shower or bath (post bath
pruritus);
fatigue
dizziness and
abdominal pain

DIAGNOSIS

The health care provider will perform a

physical exam. Tests that may be done
include:
Bone marrow biopsy
Complete blood countwithdifferential
Comprehensive metabolic panel
Erythropoietin level
Genetic test for the JAK2V617F mutation
Oxygen saturation of the blood
Red blood cell mass
Vitamin B12 level

TREATMENTS
Treatment The objective of treatment is to
reduce the high blood viscosity (thickness of
the blood) due to the increased red blood
cell mass and to prevent hemorrhage and
thrombosis. No single treatment is available
for PV. The major goal of treatment is to
prevent thrombotic events.
Aspirin therapy
(81 to 100 mg po once/day) reduces the
incidence of thrombotic complications. Thus,
patients undergoing phlebotomy alone or
phlebotomy and myelosuppression should be
given aspirinunless contraindicated. Higher
doses ofaspirinare associated with an
unacceptably increased risk of bleeding.

PHLEBOTOMY
Is a simple procedure without many risks, except for the
eventual development of iron deficiency.
The mainstay of treatment for PV is phlebotomy, which is
aimed at reducing hyperviscosity by decreasing the venous
hematocrit level.
Common thresholds for phlebotomy are Hct>45% in men
and>42% in women.
Initially, 300 to 500 mL of blood are removed every other day

Because phlebotomy is the most efficient method of

lowering the hemoglobin and hematocrit levels to
the reference range, all new patients are initially
phlebotomized to decrease the risk of complications.
The presence of elevated platelet counts that may
be exacerbated by the phlebotomy is an indication
to use myelosuppressive agents to avoid thrombotic
or hemorrhagic complications.

Myelosuppressive Therapy
The use of myelosuppressive agents such
as
radioactive
phosphorus
(32P),
chlorambucil
(Leukeran),
busulfan
(Myleran), pipobroman (Vercyte), and
hydroxyurea (Hydrea) in conjunction with
phlebotomy has been studied.
Hydroxyurea has been the mainstay
therapy for PV after the PVSG results
indicated it is an effective agent for
myelosuppression; however, concerns
have been raised regarding long-term
risks for leukemic transformation. In the
PVSG trial, HU therapy reduced the risk of
thrombosis compared with phlebotomy
alone.

Comparison of
Polycythemia Vera and
Polycythemia
Vera
Secondary
Secondary
Polycythemia
Polycythemia
Pathophysiology

Neoplastic
hematopoietic stem
cell disorder

Due to tissue hypoxia

causing an
appropriate increase
in Epo production, or
to renal or hepatic
disease causing an
inappropriate increase
in Epo production

CBC

Hct and often WBC

and platelets are
increased

Only Hct is increased

Epo level

Decreased or low
normal

Normal or increased

Treatment

Phlebotomy and/or
hydroxyurea to keep
Hct below 45%; most

Treatment is usually
not required.

Polycythemia is done!
Thank u mwaah