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 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.

That’s counterintuitive, but it’s because platelets use up free Von Willebrand factor, and low concentrations of circulating Von Willebrand factor means that it may not be enough available at the site of an injury, and that can lead to bleeding.

Now, some individuals with essential thrombocythemia can have symptoms like fatigue, headache, dizziness, nausea, tinnitus or ringing in the ears, and numbness in the hands and feet.

But more commonly, essential thrombocythemia is usually found unintentionally when elevated platelet levels are found on a routine complete blood count.

If essential thrombocythemia is suspected, a bone marrow biopsy can be done to confirm the diagnosis, Typically, lots of unusually large megakaryocytes can be seen on a bone biopsy.

Treatment of essential thrombocythemia depends on risk of blood clots. For young and healthy patients who are at low risk of blood clots or bleeding, sometimes we give aspirin and monitor the platelet counts.

When the risk of blood clots is high, therapy usually involves lowering the platelet count by using medications like hydroxyurea, interferon-alpha, and anagrelide.

In individuals with extremely high platelet counts, plateletpheresis can be used. That’s where platelets are collected and removed from the blood before the blood is returned to an individual.

All right, as a quick recap essential thrombocythemia is a slowly progressive disease where the bone marrow produces too many platelets.

Most often, it’s identified unintentionally on a routine blood test. Medication like hydroxyurea interferon-alpha, and anagrelide can be used to lower platelet counts and decrease the risk of clotting.