In vitro effect of hydroxyethyl starch on COVID-19 patients associated hypofibrinolytic state

Despite systematic thromboprophylaxis, 30% of the COVID-19 patients in intensive care units develop thrombosis. This occurrence is associated with a hypofibrinolytic state measured by thromboelastometry when adding t-PA to citrated whole blood further run for Extem® (ROTEM®). Because hydroxyethyl starches (HES) affect fibrin polymerization, we have assessed its potential effect on in vitro t-PA induced fibrinolysis.Fifteen successive COVID-19 patients from the local intensive care units were selected for t-PA resistance occurrence. HES was added to whole blood samples with proportion similar to the pharmacological recommendations. Samples were run for Extem® on a ROTEM® delta device after further addition of t-PA. Paired controls were whole blood samples added with the same saline volume. To assess the impact of HES on coagulation, thrombin generation was measured in 10 COVID-19 patients in the presence of either HES or saline then the clots obtained were used to make electron microscope images.Clot firmness at 5 minutes and the lysis index at 30 minutes was decreased in presence of HES as compared to saline (Wilcoxon test, p<0.01 for HES vs saline, and HES vs untreated). However, no statistically significant difference was observed for all TGA parameters studied (ETP, peak thrombin and time to peak). With HES, fibrin fibers of either COVID-19 patients or control subjects, were thicker compared to saline treated samples.These results highlight that HES increased apparent in vitro t-PA induced fibrinolysis in case of severe COVID-19 disease. Use of this plasma volume expander may translate as a potential help against COVID-19 induced thrombosis occurrence.