Essential thrombocythemia (NORD)

Essential thrombocythemia is a slowly progressive disease where the bone marrow produces too many platelets.

In rare cases, essential thrombocythemia can develop into myelofibrosis and acute leukemia.

Now, the vast majority of bone marrow is made of hematopoietic cells which are the early progenitor cells that can differentiate into other cell types.

In the case of platelets, progenitor cells differentiate into megakaryocytes, which are responsible for creating platelets.

In essential thrombocythemia there’s a genetic mutation that occurs in the Janus Kinase 2 gene, also called JAK2, or somewhere along this pathway of cell signalling.

Normally, the liver and kidneys produce a a tiny hormone called thrombopoietin which binds to hematopoietic cell receptors.

When it binds, those cells activate the JAK2 gene which makes them divide and mature into megakaryocytes and platelets.

Cells can also develop mutations in the thrombopoietin receptor, MPL, or in the chaperone protein, Calreticulin or CalR.

Now, when there’s a genetic mutation in CalR, the signalling pathway remains active all the time, and that means that platelets keep getting produced even in the absence of thrombopoietin.

Although there are lots of platelets that are made, many of them end up being misshapen - they’re large and irregularly shaped.

Now, all of these excess platelets end up causing an increased risk of blood clots in the deep veins of the legs, lungs, and even sites where clots don’t usually form, like the abdomen.

As a result, there’s an increased risk of stroke, heart attack, and miscarriage.

Now, if the number of platelets is extremely high, over 1.5 million, then there’s an increased risk of bleeding.