Patients with COVID-19 have special demographic characteristics including thromboembolic risk factors . The pharmacokinetics of enoxaparin administered subcutaneously in the intensive care unit patient are not described. Finally, given the lack of knowledge on the pharmacokinetic/pharmacodynamic properties of enoxaparin in intensive care unit patients infected with SARS-CoV-2, we propose to conduct a prospective multicenter cohort study to collect the biological data necessary for its study.
D-dimers greater than 1 μg/mL are a prognostic factor for 28-day mortality (odds ratio=18, 2-128). The use of preventive doses of enoxaparin (4,000 to 6,000 anti-Xa per day) or unfractionated heparin (10,000 to 15,000 IU per day) has been associated with a reduction in mortality of approximately one-third in patients with D-dimer levels greater than 3 μg/mL or those with sepsis-induced coagulopathy (SIC (sepsis-induced coagulopathy) score \> 4) For the intensive care unit patient, the preventive enoxaparin dosages were increased to 4,000 anti-Xa IU twice daily and to 6,000 anti-Xa IU twice daily if the patient weighs more than 120 kg. Curative treatment is even proposed in cases of marked inflammatory syndrome and/or hypercoagulability (e.g. fibrinogen \> 8 g/L or D-Dimer \> 3 μg/mL or 3000 ng/mL) even without symptomatic thrombosis. Given the lack of data on the use of these high "prophylactic" doses of enoxaparin, it is proposed that anti-Xa activity be monitored after the 3rd injection, and then regularly in the event of renal failure (because LMWHs are renally eliminated), to look for overdosage exposing a higher risk of bleeding. It is also proposed to regularly monitor (at least every 48 hours) the hemostasis of patients in search of multivisceral failure, or of coagulopathy of consumption which will require a re-evaluation of the heparin therapy dosage, these events being associated with an increased risk of haemorrhage.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Patients with a high thrombotic risk: In patients with a BMI included between \< 30 kg/m² and \> 30 kg/m² without added thrombotic risk factor: * Enoxaparin 40 milligrams, (4,000 IU) twice daily subcutaneously (SC) for the entire duration of the intensive care hospitalization * if weight \> 120 kg, enoxaparin 60 milligrams (6000 IU) twice daily subcutaneously for the entire duration of the intensive care hospitalization Patients with a very high thrombotic risk: In patients with a BMI \> 30 kg/m2 with added thrombotic risk factor (active cancer, recent personal history of thromboembolic event), or if iterative or unusual catheter thromboses, or if marked inflammatory syndrome and/or hypercoagulability (e.g. fibrinogen \> 8 g/L or D-Dimer \> 3 μg/ml or 3000 ng/ml) \* Enoxaparin sodium curative at a dose of 100 IU/kg/12h subcutaneously (SC) not to exceed a dose of 100 mg/12 hours
A 4-point compression ultrasound will be performed. In case of suspicion, an angiologist will perform to check the absence of legs thrombosis.
Groupement Hospitalier des portes de Province
Montélimar, France
Centre Hospitalier de Roanne
Roanne, France
CHU de Saint-Etienne
Saint-Etienne, France
Clinique Mutualiste
Saint-Etienne, France
Measure of anti-Xa activity
Measure of anti-Xa activity by chromogenic method.
Time frame: Up to 1 month
Analysis of hemorrhagic risk
Hemorrhagic risk is composite of : * Major haemorrhage as defined by the International Society on Thrombosis and Haemostasis (ISTH) definition * clinically significant haemorrhage
Time frame: Up to 1 month
Venous thromboembolic events
Venous thromboembolic events is composite of: * symptomatic or symptomatic proximal deep vein thrombosis * asymptomatic or symptomatic pulmonary embolism
Time frame: Up to 1 month
Analysis individual patient characteristics by the biomarker of Kidney function
Rate of creatinine.
Time frame: Up to 1 month
Analysis individual patient characteristics by the biomarker of inflammation
Biomarker of inflammation is composite of C-reactive protein (CRP) and inflammatory cytokines.
Time frame: Up to 1 month
Analysis individual patient characteristics by the biomarker of coagulation
Biomarker of coagulation is composite of fibrinogen and D-Dimers.
Time frame: Up to 1 month
Demographic characteristics
Analysis of weight, age, sex, height, presence of a high thrombotic risk factor (history of venous thrombotics, active cancer, invasive mechanical ventilation).
Time frame: Up to 1 month
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