Increased D-dimers at admission of COVID-19 infected patients entering hospital due to a severe disease is a risk factor for death. Understanding this acquired coagulopathy is a prerequisite before specific interventional studies. The study investigators aim to apply a normalized and automated thrombin generation test (TGT), developed for testing the thrombotic risk (triggered by 5 pM Tissue Factor, with a purified thrombomodulin (TM) challenge) and to study its association with survival.
Accumulating data describe, in COVID-19 severely infected patients necessitating hospitalized
medical support, the development of an acquired coagulopathy, from a sepsis-induced
coagulopathy to an overt-DIC, which is a strong risk factor for death. Understanding this
coagulopathy is a prerequisite before specific interventional studies. Conventional
coagulation tests, like prothrombin time PT and aPTT, only reflect 5% of the total thrombin
generation and are insensitive to the patients' natural anticoagulants. The investigators
thus wish to analyze the coagulopathy of SARS-CoV-2 using a global analytical test reflecting
the full complexity of thrombin generation then inhibition, the thrombin generation test
(TGT), in its version designed to analyze the thrombotic risk (initiation by an intermediate
concentration of human Tissue: 5 pM), in its fully automated and standardized technical
version. This test analyzes not only the generation of thrombin and its various informative
phases (initiation phase, propagation phase culminating at the peak of formation, inhibition
phase with natural anticoagulants) but also the capacity for an exogenous addition of
purified thrombomodulin (TM), which quantifies the anticoagulant activity of the patient's
protein C activated by thrombin, to inhibit this generation of thrombin.
The aim is to assay this TGT version in a centralized way, on the patients' plasma obtained
at hospital admission, just after checking the positive COVID-19 testing , together with the
traditional blood tests including platelet counts, PT, D-dimers (DDi) and soluble fibrin
monomers (FMs). The various quantitative biological parameters describing the results of the
TGT assay, together with relevant covariates, will be tested using multivariate analysis for
their capacity to be risk factors for clinically-relevant qualitative outcomes.
Other: Thrombin generation test assay
lag time, initial velocity, time-to-peak, thrombin peak, total thrombin generation time, extrinsic thrombin potential (ETP). Crude quantitative values and relative values (%, by reference to the one obtained with an invariant reference plasma). Both without the addition of purified thrombomodulin (TM-) and with the addition of purified thrombomodulin (TM+). The ability of TM to inhibit thrombin generation will be calculated as follows: [ETP (%)(TM+) / ETP (%)(TM-)].
Other: Fibrin generation markers assays
D-dimers (coagulation plus fibrinolysis), soluble fibrin monomers (coagulation only)
Inclusion Criteria:
- Patient with SARS-CoV-2 infection entering hospitalization with or without
resuscitation
- The patient (or their carer) must have given their free and informed consent and
signed the consent form
- The patient must be a member or beneficiary of a health insurance plan
Exclusion Criteria:
- Pregnant or breastfeeding patient
- It is impossible to give the subject informed information
- The patient is under safeguard of justice or state guardianship
- Thrombotic events during treatment: flare-up of venous thromboembolism, flare-up of
atherothrombosis.
- Long-term anticoagulant treatment (anti-vitamin K, direct oral anticoagulant).
- Chronic anti-aggregation treatment.
- Pre-existing constitutive or acquired known coagulation pathology: hemorrhagic
diseases (thrombocytopenia, thrombocytopathy, hemophilia, von Willebrand's disease,
hemorrhagiparous factor deficiency), and for thrombophilia (deficits in antithrombin,
protein C or S , Factor V Leiden or Prothrombin 20201A mutation).
CHU de Bordeaux
Bordeaux, France
CHU de Limoges
Limoges, France
CHU de Montpellier
Montpellier, France
CHU de Nimes
Nîmes, France
Jean-Christophe Gris, Principal Investigator
CHU Nimes