Researchers have identified blood-based markers of thromboinflammation that could improve how clinicians assess clotting risk in patients newly diagnosed with essential thrombocythaemia and polycythaemia vera, two chronic myeloproliferative neoplasms associated with life-threatening thrombosis.
Accurate thrombosis risk stratification at diagnosis is critical in these conditions, as it guides decisions on cytoreductive therapy and antithrombotic treatment. Current risk scores rely largely on age and prior thrombotic events and do not fully capture the biological processes driving clot formation. The new study suggests that inflammatory and immune-mediated pathways may offer additional insight.
Large Prospective Cohort Study
The prospective study enrolled 394 patients with newly diagnosed essential thrombocythaemia or polycythaemia vera who had not yet received cytoreductive therapy. Blood samples were collected at diagnosis, and seven plasma biomarkers reflecting neutrophil, monocyte, platelet, and endothelial activation were measured, including markers of neutrophil extracellular trap formation.
Researchers examined associations between these biomarkers and established thrombosis risk scores. Analyses were performed in the overall myeloproliferative neoplasm cohort and separately in essential thrombocythaemia and polycythaemia vera subgroups.
Distinct Patterns By Disease Type
In multivariable analyses of the full cohort, patients classified as high risk by the conventional two-tiered thrombosis score had significantly higher levels of calprotectin and tissue factor compared with low-risk patients. This association remained significant in patients with essential thrombocythaemia alone but was not observed in those with polycythaemia vera.
Patients with a JAK2V617F allele burden greater than 20% had higher levels of several biomarkers, including calprotectin, supporting a link between clonal disease burden, inflammation, and immunothrombosis. In polycythaemia vera, calprotectin levels correlated with the Venous Thrombosis Score, and five biomarkers were elevated in patients with a history of venous thrombosis, suggesting disease-specific thrombotic pathways.
Implications For Risk Stratification
The study also found that aspirin use was associated with lower levels of citrullinated histone H3 in patients with normal platelet counts, indicating a potential suppressive effect on neutrophil extracellular trap formation. This finding provides mechanistic support for the antithrombotic benefits of aspirin in selected patients.
Investigators describe this as the largest study to date linking thromboinflammation biomarkers with thrombosis risk in myeloproliferative neoplasms. They conclude that markers such as calprotectin may complement existing clinical scores and form the basis of more precise, biologically informed thrombosis risk models, potentially leading to more personalised treatment strategies for patients with essential thrombocythaemia and polycythaemia vera.
Reference
Guy A et al. Thromboinflammation is associated with high thrombotic risk in patients with newly diagnosed myeloproliferative neoplasms. Leukaemia. 2025; https://doi.org/10.1038/s41375-025-02836-8.
