NETosis and Neutrophil Activity Quantification in Pediatric Patients with Essential Thrombocythemia

Area of Science:

• Hematology
• Immunology
• Oncology

Background:

• Elevated neutrophil extracellular traps (NETs) are linked to thrombotic risks, especially in patients with high platelet counts like those with essential thrombocythemia (ET).
• Understanding neutrophil activity and NETosis is crucial for assessing thrombotic potential in ET patients.

Purpose of the Study:

• To assess the tendency for NETosis and neutrophil activity in pediatric patients with essential thrombocythemia (ET) and secondary thrombocytosis.
• To investigate potential differences in NETosis levels based on driver mutations in ET patients.

Main Methods:

• Recruited forty-one pediatric patients with ET or secondary thrombocytosis.
• Determined NETosis tendency using immunofluorescence staining on leukocyte-rich blood smears.
• Assessed neutrophil activity and chemotaxis velocity ex vivo using parallel-plate flow chambers.

Main Results:

• Patients with ET and secondary thrombocytosis exhibited elevated levels of NETosis compared to healthy volunteers.
• No significant difference in NETosis levels was observed among ET patients with different driver mutations (CALR, JAK2, triple-negative).
• Neutrophil chemotaxis velocity was significantly increased in all patient groups, particularly in those with CALR mutations.

Conclusions:

• Essential thrombocythemia and secondary thrombocytosis are associated with a significant shift in neutrophil activity, including increased NETosis and chemotaxis.
• The immunomorphological techniques used offer a reproducible method for characterizing neutrophil status in these conditions.
• These findings underscore the role of neutrophils in the thrombotic risk associated with ET.