Clonal Hematopoiesis and NETs Formation in Venous Thrombosis (CLODETTE)

University Hospital of Bordeaux

Status

Enrolling

Conditions

Clonal Hematopoiesis of Indeterminate Potential

Neutrophil Extracellular Trap Formation

Thromboembolic Disease

Venous Thromboses

Treatments

Biological: Additional blood sampling

Study type

Interventional

Funder types

Other

Identifiers

NCT05711173

CHUBX 2022/32

Details and patient eligibility

About

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.

Full description

It has recently been shown that some patients clonal have mutations at a low level in hematopoietic cells (this phenomenon is named clonal hematopoiesis of indetermined potential (CHIP)) and that the presence of a clonal hematopoiesis is associated with an increased cardiovascular risk. However, few data exist about the implication of CHIP in venous thrombosis. Neutrophils extracellular traps are involved in the activation of hemostasis and coagulation. Murine models have highlighted the crucial role of NETs in the physiopathology of venous thrombosis. In patients, studies have demonstrated that NETs markers were present in arteries lesions as coronary plaques. However, few studies have analyzed the NETosis in the setting of venous thrombosis.

The study hypothesis is that patients with venous thrombosis may have an increased prevalence of CHIP and/or an increased NETosis formation, which may represent a predisposition for the occurrence of venous thrombosis. We also speculate that patients with CHIP may have an increased NETosis, due to the presence of activating clonal mutations in neutrophils.

Patients included will be : younger than 50-years-old with repeated thrombosis or thrombosis of unusual sites (cerebral venous thrombosis, splanchnic thrombosis) with a negative etiological workup and notably the absence of constitutional or acquired venous thrombosis risk factors. In this population, we will analyze the prevalence of CHIP and the NETosis via the study of 4 different NETosis plasmatic markers.

Enrollment

150 estimated patients

Sex

All

Ages

6 to 50 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients (male or female) less than 50 y.o with :
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
1 episode of deep vein thrombosis + 1 episode of arterial thrombosis

Exclusion criteria

Presence of a major or minor transient venous thrombosis risk factor:
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
Immobilization for acute medical reasons within the last 3 months preceding the qualifying thrombotic episode
Air or car travel > 6 hours
Presence of a major or minor persistent risk factor for venous thrombosis:
Presence of active cancer (solid cancer or hematologic malignancy)
Chronic inflammatory digestive or joint diseases
Ongoing treatment with heparin (low molecular weight heparin (LMWH) or unfractionated heparin (UFH))
Presence of an abnormality on the thrombophilia test among the following abnormalities
Protein C deficiency
Protein S deficiency
Anti-thrombin deficiency
Heterozygous or homozygous factor II mutation
Heterozygous or homozygous factor V mutation
Presence of anti-phospholipid syndrome
Presence of myeloproliferative neoplasia
Presence of paroxysmal nocturnal hemoglobinuria