Myeloproliferative Neoplasm
Conditions
Keywords
Polycythemia Vera (PV), Essential Thrombocythemia (ET), Neutrophil Extracellular Trap (NET), Thrombosis
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICAL2 additional tubes of blood
2 additional tubes of blood will be collected to prepare plasma aliquots used tomeasure markers of neutrophil activation
Sponsors
University Hospital, Bordeaux
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between NET biomarkers and the risk of thrombosis | 1 day | Correlation between NET biomarkers measurated in plasma samples and the risk of thrombosis evaluated by the prognostic score IPSET thrombosis |
Secondary
| Measure | Time frame |
|---|---|
| Correlation between MPO-DNA levels (measured by absorbance at 405 nm) and a history of thrombosis | 1 day |
| Correlation between MPO-DNA levels (measured by absorbance at 405 nm) and the subtype of MPN disease (ET or PV) | 1 day |
| Correlation between MPO-DNA levels (measured by absorbance at 405 nm) and the presence of JAK2V617F mutation | 1 day |
Countries
France
Outcome results
None listed