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 tissue plasminogen activator (tPA) to citrated whole blood for a further run for EXTEM (ROTEM).

Because hydroxyethyl starches (HESs) affect fibrin polymerization, we have assessed its potential effect on in vitro tPA-induced fibrinolysis.

Fifteen successive COVID-19 patients from the local intensive care units were selected for tPA resistance occurrence. HES was added to whole blood samples with proportion similar to the pharmacologic recommendations. Samples were run for EXTEM on a ROTEM delta device after further addition of tPA. Paired controls were whole blood samples with the same volume of saline added. 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 generate electron microscope images.

Clot firmness at 5 minutes and the lysis index at 30 minutes were decreased in presence of HES compared with saline (Wilcoxon test, P < .01 for HES vs saline and HES vs untreated). However, no statistically significant difference was observed for all thrombin generation assay parameters studied (endogenous thrombin potential, peak thrombin, and time to peak). With HES, fibrin fibers of either COVID-19 patients or control subjects were thicker than those of saline-treated samples.

These results highlight that HES increased apparent in vitro tPA-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.