Thromboinflammation is associated with high thrombotic risk in patients with newly diagnosed myeloproliferative neoplasms

Thrombotic risk assessment is crucial in newly diagnosed essential thrombocythemia (ET) and polycythemia vera (PV) patients to guide cytoreductive therapy. We assessed whether thromboinflammation biomarkers would be good candidates to improve thrombosis risk stratification. We prospectively enrolled 394 newly diagnosed, cytoreductive therapy–naïve, ET and PV patients. We measured seven plasma biomarkers of neutrophil, monocyte, platelet, and endothelial activation, including NET markers, and evaluated their association with thrombosis risk scores at diagnosis. Multivariable analysis in the whole MPN cohort showed elevated calprotectin and tissue factor levels in high-risk versus low-risk patients using the conventional two-tiered score. This was also observed in ET patients only, but not in PV patients. Patients with a JAK2V617F allele burden >20% showed higher levels of three markers, including calprotectin, supporting its role in immunothrombosis. In PV patients, calprotectin correlated with the Venous Thrombosis Score (VETS), and five markers were elevated in those with prior venous thrombosis. Lastly, aspirin use was associated with lower H3Cit levels in patients with normal platelet counts, confirming its beneficial effect on NET formation. This is the largest study to date linking thromboinflammation markers to thrombotic risk in MPN patients and identifying potential biomarkers for future thrombosis risk scores.