What are the diagnostic criteria for essential thrombocytosis?

Diagnostic Criteria for Essential Thrombocythemia

The diagnosis of essential thrombocythemia (ET) requires meeting all four WHO criteria: sustained platelet count ≥450×10^9/L, bone marrow showing megakaryocytic proliferation with mature megakaryocytes, exclusion of other myeloid neoplasms, and demonstration of a clonal marker or exclusion of reactive thrombocytosis. 1, 2

WHO Diagnostic Criteria for Essential Thrombocythemia

1. Sustained platelet count ≥450×10^9/L

   • This threshold was reduced from the previous 600×10^9/L in recent WHO revisions 1, 2
   • The platelet elevation must be persistent during the diagnostic workup period

2. Bone marrow biopsy showing characteristic features

   • Proliferation mainly of megakaryocytic lineage
   • Increased numbers of enlarged, mature megakaryocytes with deeply lobulated nuclei
   • No significant increase or left-shift of neutrophil granulopoiesis or erythropoiesis
   • Megakaryocytes typically dispersed throughout biopsy sections or in loose clusters
   • Normal or only slightly hypercellular marrow for patient's age 1

3. Not meeting WHO criteria for other myeloid neoplasms

   • Polycythemia vera (PV)
   • Primary myelofibrosis (PMF)
   • BCR-ABL1–positive chronic myeloid leukemia (CML)
   • Myelodysplastic syndromes (MDS)
   • Other myeloid neoplasms 1

4. Demonstration of clonal marker or exclusion of reactive thrombocytosis

   • JAK2 V617F mutation (found in approximately 50-60% of ET patients) 3
   • CALR mutation (found in approximately 20-25% of ET patients) 4, 5
   • MPL mutation (found in approximately 4% of ET patients) 4, 5
   • In the absence of these mutations, exclusion of reactive causes of thrombocytosis is required 1, 2

Differential Diagnosis

Reactive Thrombocytosis

Must exclude common causes:

• Iron deficiency
• Splenectomy
• Recent surgery
• Infection/inflammation
• Connective tissue diseases
• Malignancy 1, 2

Other Myeloproliferative Neoplasms

• Polycythemia vera: Exclude by confirming normal hemoglobin/hematocrit or absence of increased red cell mass
• Primary myelofibrosis: Exclude by confirming absence of significant reticulin fibrosis, leukoerythroblastosis, and characteristic PMF megakaryocyte morphology
• Chronic myeloid leukemia: Exclude by confirming absence of BCR-ABL1 fusion gene
• Myelodysplastic syndromes: Exclude by confirming absence of dyserythropoiesis and dysgranulopoiesis 1

Diagnostic Approach

1. Complete blood count with peripheral smear

   • Confirm sustained platelet count ≥450×10^9/L
   • Evaluate for other cytopenias or abnormalities

2. Molecular testing

   • JAK2 V617F mutation (first-line test)
   • If JAK2 negative, test for CALR and MPL mutations
   • Approximately 90% of ET patients have one of these driver mutations 2, 4

3. Bone marrow biopsy and aspiration

   • Mandatory for diagnosis
   • Assess megakaryocyte morphology and distribution
   • Evaluate for reticulin fibrosis
   • Exclude other myeloid neoplasms

4. Cytogenetic analysis

   • Not required but may be helpful
   • Abnormal karyotype seen in <10% of patients 4

5. Exclusion of secondary causes

   • Iron studies to exclude iron deficiency
   • Inflammatory markers (ESR, CRP)
   • Evaluation for underlying malignancy if clinically indicated

Important Considerations

• Bone marrow morphology is critical for distinguishing ET from prefibrotic PMF, which can present with similar platelet counts but has different prognostic implications 1

• The presence of a JAK2, CALR, or MPL mutation strongly supports the diagnosis of ET when clinical and morphological features are consistent 2

• Pediatric ET is extremely rare with an annual incidence of approximately 1 per 10,000 in children under 14 years 6

• The diagnosis of ET in the absence of JAK2, CALR, or MPL mutations (triple-negative ET) should be made with caution and requires thorough exclusion of reactive thrombocytosis 2, 4