Evaluation of New Biomarkers of Thrombosis in Myeloproliferative Neoplasms

Evaluation of New Biomarkers of Thrombosis in Myeloproliferative Neoplasms

Thrombosis is the main cause of morbidity and mortality in patients with myeloproliferative neoplasms (MPN). However, the pathogenesis of thrombosis in MPN is still largely elusive. Neutrophils can release their decondensed chromatin as a network of extracellular fibers named NET for "neutrophils extracellular trap". NETs are known to be procoagulant. Our main objective is to quantify NETs biomarkers expression in MPN patients and define if they could be used as prognostic factors in the outcome of thrombosis in these patients.

Myeloproliferative neoplasms (MPN) are acquired clonal hematopoietic stem cell disorders, characterized by an increase in one or more myeloid lineages. The Philadelphia chromosome negative (Ph-) MPN include polycythemia vera (PV) with an excess of red blood cells, essential thrombocythemia (ET) with an increase in platelets and primary myelofibrosis (PMF). Arterial and venous thromboses are the main causes of morbidity and mortality in MPN with reported incidences ranging from 12-39% in PV and 11-25% in ET. The pathogenesis of thrombosis in MPN patients is complex and still largely elusive. The overproduction of neutrophils could be an important risk factor in the thrombus formation. Indeed neutrophils are known to promote thrombosis when they release their decondensed chromatin as a network of extracellular fibers named NET for "neutrophils extracellular trap". Increased NETosis has been reported in a mouse model of MPN. The main objective of this study is to investigate whether NET biomarkers are associated with increased thrombotic risk in patients with ET. Indeed, an international thrombotic prognostic score has been published in ET, ie the IPSET Thrombosis score (history of thrombosis, age, presence of JAK2V617F, cardiovascular risk factors).

Plasma from MPN patients will be collected, at the time of diagnosis, and measure markers of neutrophil activation, including NET biomarkers. The IPSET Thrombosis score will be evaluated in patients with ET and the correlation between the IPSET Thrombosis score and these biomarkers will be measured.

No follow-up is required for this study.

Inclusion Criteria:

• Adults (age ≥18 years),
• Patients diagnosed with Polycythemia vera (PV) or essential thrombocythemia (ET) according to WHO 2008 criteria,
• Affiliated to the national social security system,
• Signed informed consent form will be required for each included subject after having read the information note,
• Patient agreeing to be included in the FIMBANK register and having signed the corresponding consent

Exclusion Criteria:

• Adults (age >18 years), male or female,
• Patients treated with heparin or undergoing cytoreductive treatment,
• Pregnant or lactating woman,
• Person under guardianship, tutorship or other legal protection scheme or incapable of giving consent