Impact of COVID-19 associated coagulopathy in disease severity

Background : Severe COVID-19 infection is associated with a significant coagulopathy, characterized predominantly by D-dimers elevation and correlated with poor prognosis. Thromboembolic events (TE) have been identified in many patients, mostly in severe cases. Aims : The aim of this study was to characterize COVID-19 associatedcoagulopathy and to study correlations with disease-severity (DS) and outcomes (thrombosis and mortality). Methods : Seventy-nine COVID-19 patients (45M/34F;mean 70 ± 15 years-old) admitted between March and May 2020, were divided in 4 subgroups according to DS: mild ( n = 17, 21.5%), pneumonia without hypoxemia ( n = 9, 11.4%), pneumonia with hypoxemia ( n = 34, 43.0%) and multi-organic dysfunction disease ( n = 19, 24.1%). Several samples from each patient were collected and characterized according to DS, in a total of 292 samples. D-dimers, fibrinogen, PT, aPTT and blood counts were analyzed at admission and during hospitalization. Co-morbidities, TE and mortality were recorded in patients. Results : There were no significant differences in gender, age and co-morbidities between DS subgroups. D-dimers and fibrinogen at admission were significantly associated with DS ( P < 0.05 and P < 0.01, respectively). During hospitalization, there was a positive and strong correlation of DS with D-dimers, fibrinogen and platelets, and a negative correlation with hemoglobin ( P < 0.001). Venous TE (VTE) was observed in 6 patients (7.6%) and arterial TE in 3 (3.8%), which represents 17.0% (9/53) of patients in the severe stages, compared with TE incidence of 0%(0/26) in the lower stages ( P < 0.05). TE occurred in 78% of patients, despite anticoagulation prophylaxis. Overall mortality was 24.1% ( n = 19), significantly associated with DS ( P < 0.01) and with admission values of D-dimers and fibrinogen (both P < 0.05). See Table1 for results. Conclusions : These findings validate fibrinogen as another prognostic marker of COVID-19 severity and confirm the importance of coagulation changes, namely elevation of D-dimers and fibrinogen, for disease progression monitoring and prognosis prediction. In addition, TE appear to be a consequence of DS and independent of anticoagulation prophylaxis.