A 25-year-old male student presents to his family physician’s clinic for a routine physical. He feels well and has no past medical history.
- What is your differential for thrombocytosis?
- What would be your next steps in management?
Click for answer:
Diagnosis: essential thrombocytosis (ET), JAK2+
Q1: What is your differential for thrombocytosis?
See Box
Q2: What would be your next steps in management?
Rule out aVWD, consider aspirin in all patients
The differential diagnosis for thrombocytosis is broad (see Box) and includes both primary hematologic disorders as well as secondary causes.
Thrombocytosis Differential
• Primary: ET, CML, PV, myelofibrosis
• Secondary: iron deficiency, infection, inflammation (e.g. sickle cell disease), malignancy, splenectomy
If a patient has no evidence of secondary causes, further work-up should be carried out to rule out a primary hematologic disorder. This includes molecular testing to assess for the presence of a JAK2 (50% of ET), CALR (25% of ET), or MPL (5% of ET) mutation. These patients should be referred to a hematologist for further evaluation.
It is important to note that ET is associated with an increased risk of both thrombosis and bleeding. The increased risk of bleeding is secondary to platelet dysfunction as well as acquired Von Willebrand Disease (aVWD). This is particularly important to consider when the platelet count is >1,000 x 109/L. A bleeding history should therefore be carried out in all patients with ET.
CBC Pearls
- Rule out aVWD in patients with a platelet count >1,000
- ET is associated with a significant risk of thrombosis
- ASA should be considered in all patients
ET, like other myeloproliferative neoplasms, is associated with a risk of progression to acute myeloid leukemia. All patients with ET should be treated with aspirin to reduce the risk of thrombosis, and those who are high-risk (age >60 + JAK2 OR those with a thrombosis history) should be evaluated for cytoreduction (e.g. hydroxyurea).