The thrombin generation test is a global test for the study of coagulation that allows the fine study of the balance between procoagulant and anticoagulant factors. For many years, it has been performed in laboratories by semi-automated techniques, sometimes using in-house reagents, which led to a high variability and did not allow multicenter studies. Recently, an automated device for the evaluation of thrombin generation has been placed on the market (ST-Genesia), allowing a better standardization of the technique. In order to allow multicenter studies, which are essential for the routine positioning of the thrombin generation test, the inter-center variability must be evaluated, as a priority, in the pathologies for which the test is routinely positioned.

Thrombin generation (TG) assays are long-established research tools in hemostasis. They are used for both fundamental and clinical research, but a multiplicity of test methodologies limits the large adoption of TG due to the variability of results despite the attempts to standardize practices.

Several publications already exist to evaluate its analytical performances, and thereby demonstrate that the test automation also allows its democratization to reach acceptable performances It also enables the evaluation of the device in various indications such as, for example, the evaluation of the effect of direct oral anticoagulants or the evaluation of the risk of breast cancer recurrence.

The confirmation of these anterior results allows further clinical investigations in larger cohorts. However, the absence of interchangeability between the two systems indicates that the results will need to be more rugged through multicenter studies on ST Genesia.

A preliminary step in the development of multi-center protocols is to confirm that inter-center variability is acceptable on ST Genesia, and even more acceptable than it was on Calibrated Automated Thrombogram (CAT). Since the variability of the results can be attributed to analytical, pre-analytical and inter-individual biological variabilities, it has been agreed that the evaluation that we will conduct will focus only on the analytical variability and will therefore be carried out on the same samples, collected and prepared in the sponsoring center of the study, and distributed in the form of frozen aliquots to the different co-investigating centers.

The evaluation of this inter-center variability of this new device will allow, if satisfactory, to propose multicenter studies. These are essential in order to position the thrombin generation test in routine in these various promising clinical contexts.

Inclusion Criteria:

• Major patient, male or female
• Affiliated to a social security system
• In capacity to express informed consent to participate in research
• Control group: 5 men, 5 women without oral contraception, 5 women with oral contraception and apparently healthy with a respect to hemostasis (no history of thrombosis or significant bleeding on examination)
• Hemophilia groups: - 5 hemophiliacs A (treated or untreated), with predictable FVIII:C levels between < 1% and 40%.
• 5 hemophiliacs B (treated or not), with predictable FIX:C levels between < 1% and 40%.
• FV Leiden group: 5 patients known to be heterozygous or homozygous for the R506Q mutation of the F5 gene (the so-called "Factor V Leiden" mutation)
• Cirrhosis group: - 5 patients with Child-Pugh A
• 5 patients with Child-Pugh B
• 5 patients with Child-Pugh C
• Anticoagulation group: - 5 patients on anti-vitamin K therapy for at least 1 month, with INR between 2 and 4
• 5 patients on apixaban for at least 1 week
• 5 patients on rivaroxaban for at least 1 week
• 5 patients on dabigatran for at least 1 week
• 5 patients on low molecular weight heparin for at least 1 day

Exclusion Criteria:

• Refusal to participate
• Patient under protective measures (guardianship, curatorship) or under judicial protection
• Minor patients
• Moderate to end-stage renal failure
• Proven inflammatory state/infectious syndrome (body temperature > 38°C and/or clinical signs suggestive of infection) during or in the week prior to collection, at the discretion of the investigator
• Transfusion in the week prior to collection
• Pregnant or breastfeeding woman
• Contraception by estrogen-progestin, except for the control group concerned
• Anticoagulation of less than one week, except for the anticoagulation group
• Control group: - Presence of drug treatment known to interfere with hemostasis
• Presence of a pathology known to interfere with hemostasis such as renal or hepatic insufficiency
• Presence of a history of venous thromboembolic disease or diagnosed hemorrhagic disease
• Predicted inclusion hemoglobin level < 7g/L
• Hemophilic groups: - Presence of anti FVIII or anti FIX inhibitors
• Treatment with emicizumab
• Predicted inclusion hemoglobin level < 7g/L
• FV Leiden group: - Presence of anticoagulant therapy at the time of collection
• Predicted baseline hemoglobin < 7g/L
• Anticoagulation group: - Anticoagulant therapy not stabilized as determined by the practitioner
• Presence of a therapeutic relaunch in progress
• Hemoglobin at predicted inclusion < 9-10g/L
• Cirrhosis group: Predicted inclusion hemoglobin level < 7g/L

Patient taken care of at the Clermont-Ferrand University Hospital