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Essential Thrombocytosis

A N G E L I K A
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Definition
3,4

Essential
Thrombocytosis
An acquired
Myeloproliferative
disorder (MPD)
Sustained
elevation of the
platelet number
Has tendency to
thrombosis and
hemorrhage
Disease name and synonyms
3

Epidemiology
3,5,6,7

Epidemiology
> 50%
> 20%
rare

thrombotic
complications

approximately
6000 each year
( US )
Etiology
2,3,7,9,10,11,13

JAK2 (Janus kinase 2)
MPL Myelo Proliferative
Leukemia virus oncogene
THPO - Thrombopoietin
TET 2 - Tet Methylcytosine
Dioxygenase 2
Essential
Thrombocytosis
The genes which participant in
Essential Thrombocytosis
13

JAK 2 - Janus kinase 2
provides instructions for making a protein that
promotes the growth and division (proliferation)
of cells.
JAK2 protein
is part of a signaling pathway called the JAK/STAT
pathway, which transmits chemical signals from
outside the cell to the cell's nucleus.
is especially important for controlling the production
of blood cells from hematopoietic stem cells.
The genes which participant in
Essential Thrombocytosis
13

JAK 2 gene
called somatic mutations, are not inherited
are associated with ET, a disorder characterized
by an increased number of platelets, the blood
cells involved in normal blood clotting
The most common mutation (written as
Val617Phe or V617F) replaces the protein
building block (amino acid) valine with the amino
acid phenylalanine at position 617 in the protein.
The JAK2 gene related to Essential
Thrombocythemia
13


JAK 2 gene JAK 2 Protein
Mutation of V617F
JAK2
overproduction of
abnormal blood cells
called
megakaryocytes
an increased number
of platelets
( Excess platelets )
abnormal blood
clotting (thrombosis)
Sign and
sympthom of ET
The genes which participant in
Essential Thrombocytosis
13

MPL - myeloproliferative leukemia virus oncogene
provides instructions for making the
thrombopoietin receptor protein, which promotes
the growth and division (proliferation) of cells.
is especially important for the proliferation of certain
blood cells called megakaryocytes (Receptor)
is turned on (activated) when a protein called
thrombopoietin attaches (binds) to it
stimulates a signaling pathway called the JAK/STAT pathway,
which transmits chemical signals from outside the cell to the
cell's nucleus and is important for controlling the production of
blood cells (actived Receptor)

Conclusion
12,13,14

Hemolysis is the destruction or removal of
red blood cells from the circulation before
their normal life span of 120 days. While
hemolysis can be a lifelong asymptomatic
condition, it most often presents as anemia
when erythrocytosis cannot match the pace
of red cell destruction. Hemolysis also can
manifest as jaundice, cholelithiasis, or
isolated reticulocytosis.


Conclusion
12,13,14

Hemolysis presents as acute or chronic anemia, reticulocytosis, or jaundice. The
diagnosis is established by reticulocytosis, increased unconjugated bilirubin and
lactate dehydrogenase, decreased haptoglobin, and peripheral blood smear
findings. Premature destruction of erythrocytes occurs intravascular or
extravascular. The etiologies of hemolysis often are categorized as acquired or
hereditary. Common acquired causes of hemolytic anemia are autoimmunity,
microangiopathy, and infection. Immune-mediated hemolysis, caused by
antierythrocyte antibodies, can be secondary to malignancies, autoimmune
disorders, drugs, and transfusion reactions. Microangiopathic hemolytic anemia
occurs when the red cell membrane is damaged in circulation, leading to
intravascular hemolysis and the appearance of schistocytes. Infectious agents
such as malaria and babesiosis invade red blood cells. Disorders of red blood cell
enzymes, membranes, and hemoglobin cause hereditary hemolytic anemias.
Glucose-6-phosphate dehydrogenase deficiency leads to hemolysis in the
presence of oxidative stress. Hereditary spherocytosis is characterized by
spherocytes, a family history, and a negative direct antiglobulin test. Sickle cell
anemia and thalassemia are hemoglobinopathies characterized by chronic
hemolysis.
Conclusion
12,13,14

Hemoglobin consists of an iron-containing heme ring and four globin
chains: two alpha and two nonalpha. The composition of the four globin
chains determines the hemoglobin type. Fetal hemoglobin (HbF) has two
alpha and two gamma chains (alpha2 gamma2). Adult hemoglobin A
(HbA) has two alpha and two beta chains (alpha2 beta2), whereas
hemoglobin A2 (HbA2) has two alpha and two delta chains (alpha2
delta2). At birth, HbF accounts for approximately 80 percent of
hemoglobin and HbA accounts for 20 percent.
The transition from gamma globin synthesis (HbF) to beta globin
synthesis (HbA) begins before birth. By approximately six months of age,
healthy infants will have transitioned to mostly HbA, a small amount of
HbA2, and negligible HbF.
The thalassemias (named from the Greek word for sea, thalassa
12
) are a
group of inherited autosomal recessive hematologic disorders
13
that
cause hemolytic anemia because of the decreased or absent synthesis of
a globin chain. Imbalances of globin chains cause hemolysis and impair
erythropoiesis.
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