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Essential Thrombocytosis

A N G E L I K A

0 3 0 . 0 9 . 0 2 0

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Definition3,4

EssentialThrombocytosis

An acquiredMyeloproliferative

disorder (MPD)

Sustained

elevation of theplatelet number

Has tendency tothrombosis and

hemorrhage

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Disease name and synonyms3

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Epidemiology3,5,6,7

Epidemiology

> 50%

> 20%

rare

thrombotic

complications

approximately

6000 each year

( US )

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Etiology2,3,7,9,10,11,13

JAK2 (Janus kinase 2)MPLMyelo ProliferativeLeukemia virus oncogene

THPO - ThrombopoietinTET 2 - Tet Methylcytosine

Dioxygenase 2

EssentialThrombocytosis

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The genes which participant in

Essential Thrombocytosis13

JAK 2 - Janus kinase 2

provides instructions for making a protein thatpromotes the growth and division (proliferation)

of cells.JAK2 protein

is part of a signaling pathway called the JAK/STATpathway, 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.

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The genes which participant in

Essential Thrombocytosis13

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 proteinbuilding block (amino acid) valine with the amino

acid phenylalanine at position 617 in the protein.

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The JAK2 gene related to Essential

Thrombocythemia13

JAK 2 gene JAK 2 ProteinMutation of V617F

JAK2

overproduction ofabnormal blood cells

calledmegakaryocytes

an increased numberof platelets

( Excess platelets )

abnormal bloodclotting (thrombosis)

Sign andsympthom of ET

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The genes which participant in

Essential Thrombocytosis13

MPL - myeloproliferative leukemia virus oncogene

provides instructions for making thethrombopoietin 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 calledthrombopoietin attaches (binds) to it

stimulates a signaling pathway called the JAK/STAT pathway,which transmits chemical signals from outside the cell to thecell's nucleus and is important for controlling the production of

blood cells(actived Receptor)

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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 canmanifest as jaundice, cholelithiasis, or

isolated reticulocytosis.

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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 cellenzymes, 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.

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Conclusion 12,13,14

Hemoglobin consists of an iron-containing heme ring and four globinchains: 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, thalassa12) are a

group of inherited autosomal recessive hematologic disorders13that

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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