Bleeding disorders associated with severity of respiratory failure in COVID-19 patients: a prospective observational study

Abstract

INTRODUCTION: Despite the progress in understanding the pathophysiology of coagulopathy in COVID-19, data about the association and phasing of pathological changes in various parts of the hemostatic system with the development of acute respiratory distress syndrome (ARDS) are insufficient. OBJECTIVE: To determine association between the severity of respiratory failure and pathological changes in the hemostatic system in COVID-19 patients. MATERIALS AND METHODS: A prospective observational study included 204 patients with a confirmed diagnosis of severe and extremely severe COVID-19. Two groups were identified according to disease outcome: fatal (n = 106) and survived (n = 98) groups. To assess dynamics of the clinical picture of the disease and to study the hemostatic profile, time points were determined: I point — the first day — admission to intensive care unit; II point — 3–5 days, III point — 7–10 days after ICU admission. The respiratory index was calculated to assess the severity of respiratory distress syndrome. Statistical data processing was carried out using the statistical software package MedCalc Version 20.110 (MedCalc Software Ltd, Belgium). RESULTS: A 2.15-fold decrease in the respiratory index was determined for fatal outcome in patients with severe and extremely severe COVID-19. The most important hemostatic parameters affecting the severity of respiratory failure are increased Willebrand factor concentration at I point of the study (21 % contribution and inverse correlation), increased plasminogen activator inhibitor type 1 (PAI-1) level on 3–5 days (35 % contribution and direct correlation), and activation of the coagulative component of hemostasis on 7–10 days (78 % contribution and direct correlation). CONCLUSIONS: The severity of respiratory failure in patients with a confirmed diagnosis of severe and extremely severe COVID-19 is gradually associated with endotheliopathy (1 day), inhibition of parietal fibrinolysis (3–5 days) and activation of the coagulative component of hemostasis by 7–10 days of ICU stay.