Clinical trial NCT04177576: Evaluation of New Biomarkers of Thrombosis in Myeloproliferative Neoplasms
Official title: Evaluation of New Biomarkers of Thrombosis in Myeloproliferative Neoplasms
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myeloproliferative Neoplasm
Keywords: Polycythemia Vera (PV)
Essential Thrombocythemia (ET)
Neutrophil Extracellular Trap (NET)
Thrombosis
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2019-11-26
Enrollment: 397
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with myeloproliferative neoplasms (MPN), diagnosed with Polycythemia vera (PV) or essential thrombocythemia (ET)

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.

Eligibility criteria: 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

Primary outcomes:
measure: Correlation between NET biomarkers and the risk of thrombosis
timeFrame: 1 day
Secondary outcomes:
measure: Correlation between MPO-DNA levels (measured by absorbance at 405 nm) and a history of thrombosis
timeFrame: 1 day
measure: Correlation between MPO-DNA levels (measured by absorbance at 405 nm) and the subtype of MPN disease (ET or PV)
timeFrame: 1 day
measure: Correlation between MPO-DNA levels (measured by absorbance at 405 nm) and the presence of JAK2V617F mutation
timeFrame: 1 day
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Annecy
country: France
facility: CH Annecy Genevois
city: Avignon
country: France
facility: CH Avignon
city: Bordeaux
country: France
facility: CHU Bordeaux, Hématologie Biologique
city: Bordeaux
country: France
facility: CHU Bordeaux, Hématologie Clinique et Thérapie Cellulaire
city: Bordeaux
country: France
facility: CHU Bordeaux, Médecine Interne
city: Bordeaux
country: France
facility: Institut Bergonié
city: Brest
country: France
facility: CHRU Brest
city: Créteil
country: France
facility: CHU Henri Mondor - APHP
city: Dax
country: France
facility: CH Dax
city: Dijon
country: France
facility: CHU Dijon
city: Limoges
country: France
facility: CHU Limoges
city: Lyon
country: France
facility: Centre Léon Bérard
city: Mont-de-Marsan
country: France
facility: CH Mont de Marsan
city: Nancy
country: France
facility: CHU Nancy
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou - APHP
city: Paris
country: France
facility: Hôpital Saint-Louis - APHP
city: Perpignan
country: France
facility: CH Perpignan
city: Poitiers
country: France
facility: CHU Poitiers
city: Rochefort
country: France
facility: CH Rochefort
city: Roubaix
country: France
facility: CH Roubaix
city: Toulouse
country: France
facility: IUCT-Oncopôle
city: Valenciennes
country: France
facility: CH Valenciennes
city: Villejuif
country: France
facility: Hôpital Paul Brousse
Study officials:
affiliation: University Hospital, Bordeaux
name: Chloé JAMES
role: PRINCIPAL_INVESTIGATOR
References: