Prognostic Value of NETosis Markers for Thrombosis During Myeloproliferative Neoplasms (AVATARE)

Prospective Study for the Evaluation of the Prognostic Value of NETosis Markers to Predict Thrombosis in Myeloproliferative Neoplasms With JAK2V617F Mutation (AVATARE)

Myeloproliferative neoplasms are hematologic diseases characterized by an increased proliferation of peripheral blood cells. The main risk of MPN is the occurrence of thrombosis. Thrombosis risk is mainly evaluated using two criteria: age and prior thrombosis. A better prediction of thrombosis risk is needed to improve prevention and treatment of MPN-associated thrombosis. The objective of the study is to evaluate the predictive value of neutrophil extracellular traps markers in thrombosis during MPN.

JAK2V617F positive myeloproliferative neoplasms (MPNs) are clonal disorders of hematopoietic stem cells characterized by an increased risk of thrombosis, the main cause of morbidity and mortality in these patients. Classical risk factors for thrombosis include a prior thrombotic event and age over 60. However, these criteria are often insufficient, as some patients who receive treatment continue to experience thrombosis, while others may be overtreated based solely on age. Recent studies have highlighted the role of neutrophil extracellular traps (NETs) in thrombosis, suggesting that NETosis, the process of NET formation, contributes to the activation of hemostasis and coagulation. Increased levels of NETs have been observed in patients with MPNs, particularly those with a history of thrombosis. Aspirin has shown a potential to reduce NET formation and the occurrence of thrombosis by inhibiting platelet-triggered NETosis. This study aims to prospectively evaluate the prognostic value of NETosis markers to predict thrombosis and optimize thrombotic prevention strategies in JAK2V617F-positive MPN patients.

The AVATARE ancillary study is linked to the AVAJAK clinical trial, which compares the efficacy of aspirin versus direct oral anticoagulants (DOACs) in preventing thrombotic events. Patients included in the AVATARE study will undergo venous blood sampling at baseline (T0) and 12 months (T1) for NETosis markers, such as calprotectin and citrullinated histone H3 (H3Cit). Participants will be followed up for 24 months. Clinical data, including the occurrence of venous and arterial thrombotic events, will be collected during the study period. Blood samples will be taken at inclusion (T0) and at 12 months (T1). The progression of NETosis markers will be monitored, and their correlation with thrombotic outcomes will be assessed to understand the potential role of these markers in predicting future thrombotic events.

Inclusion Criteria:

• Diagnosis of Polycythemia Vera (PV), Essential Thrombocythemia (ET), or pre-myelofibrosis (pre-MF)
• JAK2V617F mutation with an allelic burden greater than 1%
• High risk of thrombosis (age over 60 years or prior thrombotic event)
• Diagnosis of MPN within the last 12 months
• Enrollment in the AVAJAK clinical trial and the FIMBANK biobank
• Affiliation with social security
• Signed informed consent

Exclusion Criteria:

• Severe hepatic or renal insufficiency (Creatinine clearance <30ml/min)
• Patients under legal protection (guardianship or curatorship)
• Patients under heparin treatment at inclusion