AssessmentsEssential thrombocythemia (NORD)
Essential thrombocythemia (NORD)
USMLE® Step 1 style questions USMLE
A 68-year-old male comes to his provider’s office for evaluation of fatigue, weakness, and 8 kg (17.6 lb) unintentional weight loss over the past 2 months. Moreover, the patient reports feeling bloated after eating small quantities of food during this same time period. His past medical history is notable for hypertension, and the patient is currently taking hydrochlorothiazide. Physical exam reveals oral mucosal pallor. Cardiac and pulmonary exams are non-contributory. Abdominal exam reveals hepatosplenomegaly. Laboratory testing results are as follows:
Laboratory value Result Hemoglobin 9.5 g/dL Hematocrit 28.5% Leukocytes 2,700/mm3 Platelets 100,000/mm3
Biopsy of the bone marrow biopsy shows increased fibrosis and reduced cell count. Polymerase chain reaction testing reveals a mutation in a gene encoding for a non-receptor tyrosine kinase. Which of the following diseases is also caused by an identical mutation?
Content Reviewers:Rishi Desai, MD, MPH
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 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.
Now, if the number of platelets is extremely high, over 1.5 million, then there’s an increased risk of bleeding.