Involvement of the contact pathway in COVID-19 coagulopathy

A novel acquired coagulopathy characterized by severe procoagulant imbalance is common and associated with the clinical severity in COVID-19 patients. To elucidate the underlying mechanisms of coagulation activation in COVID-19 patients. Symptomatic COVID-19 patients were consecutively enrolled and stratified into 3 groups based on the intensity of care. Markers of intrinsic (FXIa, FXIIa) and extrinsic (FVIIa) pathway activation and of fibrinolysis (plasminogen and relative activator and inhibitors), D-dimer, fibrin monomer (FM), fibrin degradation products (FDP), and C1 inhibitor were tested. A total of 111 patients were enrolled, 26 in the low, 42 in the intermediate, and 43 in the high intensity of care group. Median D-dimer, FDP, and FM plasma levels were higher in COVID-19 patients than normal ranges, with a gradient of increase across the three intensity care units; the fibrinolytic pathway parameters were in the normal range. The median plasma levels of FVIIa were lower in COVID-19 patients (27.5 mU/mL) than the reference range while the median plasma levels of FXIIa and FXIa were higher (11.2 and 11.3 mU/mL), with a gradient of increase across the three intensity care units for FXIIa. C1 inhibitor plasma levels were above the normal range in all the 3 COVID-19 patient groups. 32 patients (29%) developed a venous thrombosis. Our study suggested a prevalent activation of the contact pathway over the extrinsic pathway of the coagulation cascade in COVID-19 patients, which is proportional to the clinical severity of the infection, opening the possibility for targeted anticoagulant therapies.