Thrombo-embolic venous diseases are represented by deep venous thrombosis and/or pulmonary embolism. In some patients with repeated thrombosis or occurrence of thrombosis in unusual sites, the etiological workup remains negative, which represents a problem for the management of the anticoagulant treatments. Recently, two factors have been identified as important in the physiopathology of hemostasis and coagulation: the presence of clonal hematopoiesis of indetermined potential (CHIP) and the formation of neutrophil extracellular traps (NETs). In this study, these two factors will be studied in patients with repeated venous thrombosis or thrombosis occurring in unusual site.
Splanchnic venous territory thrombosis or
Cerebral venous thrombosis or
Venous thrombosis of the upper limb or
Pulmonary embolism (1st episode if male, 2nd episode if female) unprovoked or
Surgery within the last 3 months preceding the qualifying thrombotic episode
Lower limb fracture with immobilization > 3 days in the last 3 months preceding the qualifying thrombotic episode
Presence of estro-progestational contraception
Pregnancy
Single group
Additional blood sampling
Biological/VaccineThe procedure will consist of an additional blood sample for ETDA tube collection (NGS analysis) and citrate tube collection (NETose analysis)
Presence of clonal hematopoiesis
The existence of clonal hematopoiesis will be defined as the demonstration of at least one mutation in the blood cells of an apparently healthy subject (without obvious hematological pathology). DNA will be extracted from circulating leukocytes to search for mutations in a panel of 59 genes
Presence of one or more increased NETosis markers and/or a decreased NETosis-inhibiting marker (DNAse level) compared to a control population.
Analysis of the following markers: MPO-DNA complex, Histone 3-DNA complex, citrullinated histone 3, DNAse
Correlation (correlation coefficient values) between the presence of a CHIP and the formation of NETs
Correlation analysis will be performed between each NETosis marker and CHIP evaluation (presence or absence, number of mutations, variant allele frequency for each mutation)
Allele frequency
Variant allele frequency of each detected mutation will be determined using NGS analysis
Number of clonal mutations
The number of clonal mutations for each patient will be determined using NGS analysis
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