Thrombin generation (TG) reveals underlying hypercoagulable process in COVID-19 patients despite low molecular weight heparin (LMWH) therapy

Background : Infection with SARS-CoV-2 is responsible for systemic inflammation and consequent coagulation activation. Therapeutic or prophylactic LMWH choices might influence the procoagulant state. Aims : To determine the coagulation and inflammation parameters and to investigate the hypercoagulable process of COVID-19 patients receiving LMWH, employing TG assay. Methods : All hemostasis measurements were performed on the Sta Compact (Stago). C -Reactive Protein (CRP) by immunoturbidimetric assay . TG was determined by CAT (Thrombinoscope BV) triggered with 5 pM TF. The parameters evaluated were: lag time (LT), peak time (ttP), endogenous thrombin potential (ETP) and thrombin peak (peak height). Patients with moderate COVID-19 admitted to the General ward (GW) or in the intensive care unit (ICU), were included. A group of patients at GW were receiving enoxaparin 40 mg sc once daily (group B) and the patients at ICU received 0.5 mg/kg sc BID (group C). No Covid-19 patients at GW were used as control group (group D). Results : At the GW, there weren't difference in fjbrinogen and CRP values between group A and group B, but both were higher than group D. Group A showed lower D-dimer values compared with group B ( P 0.01) and C ( P 0.037).Group C had increased fibrinogen levels compared with Covid-19 patients admitted to the GW ( Group A, B) .No significant differences were found in TG (Peak, ETP and ttP) between Group A and B but Group C had a lower ETP and longer LT than those in the GW, despite that, Group C, had similar thrombin generation than control group (ETP C vs D P 0.89, Peak CvsD P 0.57). Conclusions : Our results show that TG is a useful test to demostrate the hypercoagulable state in patients with COVID-19. In adittion TG assay revels that standard LMWH doses could be inefficient in critical patients.