INVOLVEMENT OF THE CONTACT PATHWAY IN COVID-19 COAGULOPATHY

Background. A novel acquired coagulopathy characterized by a severe procoagulant imbalance is common in COVID-19 patients and is associated with the clinical severity of the disease. Aims. Our study aims at elucidating the underlying mechanisms of coagulation activation in COVID- 19 patients. Methods. The study is composed of two phases. In the first and second part, 62 and 112 symptomatic COVID-19 patients, respectively, were consecutively enrolled and stratified into 3 groups based on the intensity of care: low, requiring only high-flow oxygen by nasal cannula (21 and 23 patients); intermediate, requiring continuous positive airway pressure (20 and 47 patients); high, requiring mechanical ventilation (20 and 42 patients). During the first phase of the study blood samples were tested for markers currently used to diagnose disseminated intravascular coagulation (DIC) (PT, aPTT, fibrinogen, D-dimer, platelet count), the pro- (FII, FVIII) and anticoagulant factors (antithrombin, protein C, protein S) and those indicating endothelial perturbation (von Willebrand factor). During the second phase of the study blood samples were tested for markers of activation of the intrinsic pathway (FXI, FXII, FXIa, FXIIa) together with its physiologic inhibitor (C1-inhibitor), of the extrinsic pathway (FVII, FVIIa), global activation of the coagulation cascade (D-dimer, FDP, FM) and fibrinolysis (plasminogen, t-PA, 𝛼2-antiplasmin, PAI-1). Results. Results of the first phase of the study demonstrated that COVID-19 coagulopathy represents a new entity, not fulfilling the criteria for DIC, characterized by endothelial activation, while the second part of the study showed a prevalent activation of the contact pathway over the extrinsic pathway of the coagulation cascade. Conclusions. Our study showed an acquired coagulopathy associated with hyperacute inflammation, hypercoagulability, and endothelial perturbation proportional to the clinical severity 3 of the infection, characterized by a prevalent activation of the intrinsic pathway of the coagulation cascade, opening the possibility for targeted therapies.