Essential Thrombocythemia

Topic 04 · Myeloproliferative Neoplasms

Ashwin Kishtagari, MBBS, MSCI

Division of Hematology/Oncology, Vanderbilt University Medical Center

2026-08-18

Overview

What is essential thrombocythemia?

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by sustained overproduction of platelets.

  • Clonal disorder of the hematopoietic stem cell
  • Persistent thrombocytosis (platelets typically > 450 × 10⁹/L)
  • Increased risk of both thrombosis and hemorrhage

Where ET sits among the MPNs

The classic BCR-ABL1–negative myeloproliferative neoplasms:

  • Essential thrombocythemia (ET) — platelet-predominant
  • Polycythemia vera (PV) — red-cell-predominant
  • Primary myelofibrosis (PMF) — marrow fibrosis

Pathophysiology

Driver mutations

Three mutually exclusive driver mutations account for most cases:

Mutation Approx. frequency
JAK2 V617F ~50–60%
CALR ~20–25%
MPL ~3–5%
Triple-negative ~10–15%

All converge on dysregulated JAK-STAT signaling.

The JAK-STAT pathway

  • Mutations cause constitutive activation of JAK-STAT
  • Drives megakaryocyte proliferation independent of thrombopoietin
  • Result: sustained thrombocytosis

Clinical Presentation

How patients present

  • Often asymptomatic — found incidentally on routine CBC
  • Vasomotor symptoms: headache, dizziness, erythromelalgia
  • Thrombotic events (arterial > venous)
  • Bleeding (especially with very high platelet counts)

Major complications

Thrombosis

  • Stroke, TIA
  • Myocardial infarction
  • Deep vein thrombosis
  • Unusual sites (splanchnic)

Hemorrhage

  • Mucocutaneous bleeding
  • Acquired von Willebrand syndrome
  • Risk rises at extreme thrombocytosis

Diagnosis

Diagnostic approach

  1. Confirm sustained thrombocytosis on repeat CBC
  2. Exclude reactive (secondary) causes — iron deficiency, infection, inflammation, malignancy
  3. Test for driver mutations (JAK2, CALR, MPL)
  4. Bone marrow biopsy — large, mature megakaryocytes with hyperlobulated nuclei
  5. Exclude other MPNs and myelodysplastic syndromes

Reactive vs. clonal thrombocytosis

Always distinguish ET from a reactive process before committing to the diagnosis:

  • Reactive: identifiable trigger, normal driver mutation testing
  • Clonal (ET): driver mutation present and/or characteristic marrow morphology

Risk Stratification & Management

Risk stratification

Risk is driven primarily by thrombosis risk, guided by:

  • Age (older = higher risk)
  • Prior thrombotic history
  • JAK2 mutation status
  • Cardiovascular risk factors

Management principles

  • Low-dose aspirin for most patients (manage vasomotor symptoms / thrombosis risk)
  • Cytoreduction (e.g. hydroxyurea) for higher-risk patients
  • Manage cardiovascular risk factors
  • Caution with aspirin at extreme platelet counts (bleeding risk)

Warning

Treatment decisions should follow current clinical guidelines and specialist input. This deck is for educational structure, not clinical guidance.

Summary

  • ET is a chronic MPN defined by clonal thrombocytosis
  • Driven by JAK2, CALR, or MPL mutations via JAK-STAT
  • Key risks are thrombosis and hemorrhage
  • Diagnosis requires excluding reactive causes
  • Management is risk-adapted