Platelet activation and neutrophil extracellular trap (NET) formation in immune thrombocytopenia: is there an association?

Abstract

No biological predictors for the increased risk of thrombosis in patients with immune thrombocytopenia (ITP) have been identified. The aim of the study was to investigate platelet and neutrophil activation as well neutrophil extracellular trap (NET) formation in 63 ITP patients and 30 healthy volunteers. Platelet and neutrophil activation was assessed during steady state using flow cytometry analysis, and NETs were evaluated by quantitation of cell free DNA (cfDNA), and citrullinated histone-3-DNA (CitH3-DNA). Patient platelets and neutrophils showed increased CD62 and CD11b expression compared to controls (p = .038, and p = .022, respectively). In patients, platelet activation inversely correlated with platelet count and platelet size (p < .001), and positively correlated with neutrophil degranulation (p = .024). More NET formation, both CitH3-DNA (p = .025) and cfDNA(p < .001), were present in ITP patients compared to controls. CitH3-DNA inversely correlated with CD62 expression on platelets (p = .042), but higher levels of cfDNA were observed in individuals with classical cardiovascular risk factors for thrombosis, and in those with a previous history of thrombotic events. In this disease, the increased platelet activation and plasma NET levels seem to be separable processes that associate (either positively or inversely in the case of CitH3-DNA or platelet degranulation, respectively) to platelet mass.

Keywords:

• ITP
• NETs
• thrombosis

Acknowledgements

Research from the authors group is supported by grants from Instituto de Salud Carlos III/FEDER (PI17/01311, and PI7/0051), CIBERER (CB15/00055), and Fundación Séneca (19873/GERM/15). AMR-G and SA hold a pre-doctoral contract (PFIS 18/0045)and a Sara Borrell contract (CD18/00044), respectively, from Instituto de Salud Carlos III/FEDER.

Declaration of Interest

The authors declare no conflicts of interest

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Additional information

Funding

This work was supported by the Fundación Séneca [19873/GERM/15]; Instituto de Salud Carlos III [CB15/00055,PI17/01311,PI7/0051].