Background: Thrombosis is a life-threatening major event in severe coronavirus disease 2019 (COVID-19) affecting the lung as evidenced by autopsy reports of pulmonary intravascular microthrombi. The new coronavirus (CoV) does not appear to have intrinsic procoagulant effects itself. The coagulation changes in COVID-19 are likely a result of the inflammatory response. Significant inflammation is present in COVID-19, based on elevated interleukin-6 (IL-6). This inflammation associated with COVID-19 results in coagulopathy, based on elevated D-dimer (DD). An endotheliopathy appears to contribute to microvascular thrombosis in COVID-19. Aim of this study is to confirm the coagulation abnormalities in 100 severe COVID-19 patients having lung involvement and their association with the severity and prognosis. Methods: Inflammation, endothelial and coagulation indicators were performed and compared between severe and mild disease. Findings: IL-6 and TNF-a, and TF and VWF, exceeded in severe COVID-19 as well as D-dimer, TAT, and Fibrinogen. As PF4 hasa rapid removal from plasma, we also measured b-TG levels which exceeded the plasma levels of PF4 in severe COVID-19 patients as well as increased platelet adhesion was observed. Shortened CT and CFT, high MCF and low LY at 30 minutes were present in 100% of severe COVID-19 patients compared with mild COVID-19 patients. It is reported that TFPI is a natural anticoagulant that lowes inflammation and coagulation. Therefore, we measuredTFPI levels which exceeded without shutdown of the inflammation and coagulation. Interpretation: The thrombotic pathogenesis in severe COVID-19 harbors in profound inflammation and severe coagulation as documented by blunted TFPI levels.Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: Each study participant gave written informed consent for study enrollment in accordance with the Declaration of Helsinki. This study has been approved by an internal committee at the "Haematology/Haemostasis Unit "- University of Catania.