Inflammation and abnormalities in laboratory coagulation tests are inseparably tied. For example, coagulation abnormalities are nearly universal in septic patients. Coagulation disorders have also been reported in many patients with severe courses of Coronavirus disease 2019 (Covid-19). But it is difficult to assess these changes. Global coagulation tests have been shown to incorrectly assess in vivo coagulation in patients admitted to intensive care units. But other tests are available. Thrombin generation assay (TGA) is a laboratory test which allows the assessment of an individual's potential to generate thrombin. But also in conventional TGA the protein C system is hardly activated because of the absence of endothelial cells (containing natural thrombomodulin) in the plasma sample. Therefore the investigators add recombinant human thrombomodulin to a conventional TGA. Thereby the investigators hope to be able to depict in vivo coagulation more closely than global coagulation tests do.
Diagnostic Test: Thrombin Generation Assay (TGA)
TGA via a fluorimetric module. Coagulation cascade is activated upon addition of different concentrations of tissue factor and phospholipids. The fluorogenic substrate Z-Gly-Gly-Arg-AMC (ZGGR-AMC) is cleaved by formed thrombin over time. By plotting the changes in fluorescence as a function of time (cnt/min), it depicts the "Thrombin Generation Curve" (thrombin generated - plotted against time). The area under the thrombin curve is defined as the endogenous thrombin potential (ETP).
Diagnostic Test: Thrombomodulin Modified Thrombin Generation Assay (TGA-TM)
Recombinant Human Thrombomodulin (TM) is added to the conventional TGA. When recombinant TM is added, the protein C system is fully activated and therefore the ETP obtained reflects both the anti- and procoagulant factors.
- Admission to ICU
- Clinical signs of infection with SARS-CoV-2 or already diagnosed infection with
- Neutrophil-Lymphocyte Ratio (NLR) >3
- Intake of oral anticoagulants or any kind of parenteral therapeutic anticoagulation
prior to ICU admission
- Congenital coagulation disorder
- Treatment with Prothrombin complex concentrate (F. II, VII, IX, X) or activated
Prothrombin complex within past 48 hours
- Treatment with recombinant factor VIIa (e.g. eptacog alfa) within past 48 hours
- Treatment with recombinant protein C within past 48 hours
- Active bleeding
- Acute myocardial infarction
- HIV infection
- Chronic pancreatitis
- Liver cirrhosis
Medical University Vienna