Chapter 1

Polycythemia vera

What is Polycythemia Vera?

Polycythemia vera (PV) is a medical bone marrow disorder in which there is an uncontrolled proliferation of the blood cells.

All the blood cells in the body are involved.

Polycythemia rubra vera (PRV) mainly produces too many red blood cells.

The number of white blood cells and platelets may be higher as well.

It is believed to be a benign form of neoplasm giving rise to a chronic disease from which the patient eventually dies.

What is the cause of Polycythemia vera?

Cause:

The exact cause is not known but it is often linked to a gene defect called JAK2V617F.

The reason behind this gene defect is not known.

Polycythemia vera (PV) is produced by somatic mutation in a single hematopoietic stem cell.

This mutation can be investigated only in female patients, as it makes use of polymorphisms on the X-chromosome and takes advantage of its inactivation.

The red cells are normally responsive to erythropoietin but they do not depend upon it to multiply.

There is a danger of transformation to acute myeloid leukemia.

PV is a myeloproliferative disorder with mainly erythrocyte hyperplasia, but also myeloid leukocytosis, thrombocytosis and splenomegaly

Polycythemia Primary Causes

In primary polycythemia, inherited or acquired problems with red blood cell production result in polycythemia.

There are two main disorders that place it in the primary polycythemia category:

1. Polycythemia vera (PV) or polycythemia rubra vera (PRV)

Polycythemia vera (PV) is linked to a genetic mutation in the JAK2 gene which is believed to raise the sensitivity of bone marrow cells to a hormone called erythropoietin (Epo), leading to higher red blood cell production.

The levels of other forms of blood cells (white blood cells and platelets) are also often higher in this disorder.

2. Primary familial and congenital polycythemia (PFCP).

Primary familial and congenital polycythemia (PFCP) is a disorder linked to a mutation in the EPOR gene and induces higher production of red blood cells in response to erythropoietin (Epo).

Polycythemia Secondary Causes

In contrast to primary polycythemia in which there is excess production of red blood cell occurring from higher sensitivity or responsiveness to Epo (with reduced levels of Epo), in secondary polycythemia, more red blood cells are formed because of highly raised levels of circulating Epo.

The main reasons for higher levels of Epo are:
1. Chronic hypoxia (low blood oxygen levels over the long-term),
2. Low oxygen delivery due to abnormal red blood cell appearance, and
3. Tumors releasing inappropriately higher amounts of Epo.

There are frequent disorders that can lead to higher erythropoietin level due to long term hypoxia or low oxygen supply:

a. Chronic obstructive lung disease (COLD, emphysema, chronic bronchitis),
b. Pulmonary hypertension,
c. Hypoventilation syndrome,
d. Congestive heart failure,
e. Obstructive sleep apnea,
f. Poor blood flow to the kidneys, and
g. Living in high altitudes.

The disorder in which the hemoglobin molecule in the red blood cells has an abnormal appearance is 2,3-BPG deficiency.

The hemoglobin in this disorder has a higher affinity to keep the oxygen and decreased ability to release it to the tissues.

Consequently, the higher amount of red blood cells are being produced in response to what the tissues in the body observe as a low oxygen level.

The effect is a higher levels of circulating red blood cells.

TABLE OF CONTENT
Introduction
Chapter 1 Polycythemia Vera
Chapter 2 Causes
Chapter 3 Symptoms
Chapter 4 Diagnosis
Chapter 5 Treatment
Chapter 6 Prognosis
Chapter 7 Polycythemia Rubra Vera
Chapter 8 Myeloproliferative disease
Epilogue