Pulmonary Vascular Thrombosis in COVID-19: Clinical and Morphological Parallels

Abstract

Aim. We aimed to study the histological and thrombotic changes in lung vessels in patients who died with COVID-19, to access the correlation between anticoagulation therapy (ACT) and thrombotic events (TE), treatment results, clinical and laboratory patients' characteristics.Material and Methods. We retrospectively analyzed treatment results of patients hospitalized with COVID-19 and lung vessel samples of the deceased patients. Dynamic changes and highest levels of D-dimer and fibrinogen were studied in its correlation with the disease severity according to SOFA score, computer tomographic (CT) results, lung, renal and hepatic dysfunction. The association between different doses of ACT and treatment results, laboratory indicators and thrombotic events was accessed. The histological lung vessels examination was performed using Martius Scarlet Blue (MSB)staining.Results. 313 patients were included in the study (61 patients died). The median age of hospitalized patients was 60 years (IQR 51-66 years). The frequency of the intravitallyconfirmed TE was 4,8%. The strong statistical association was revealed between D-dimer level and 3-4 points SOFA score, patients' mortality, oxygen support requirement, CT3-CT4 pneumonia, glomerular filtration rate and TE. There was no mortality in patients with D-dimer normal references, but in cases with three times elevation reached 13%, 48,5% - in cases with 3-6 times elevation and 64,6% - in cases with more than 6 times elevation. The strong statistical association was registered between fibrinogen and SOFA score, CT 3-4 pneumonia, patients' mortality. D-dimer and fibrinogen levels demonstrated weak correlation. There was no statistical correlation between prophylactic, intermediate and therapeutic ACT and D-dimer and fibrinogen levels, CT results, patients' mortality. MSBstaining was used in 36 deceased patients tissue samples. 1394 lung vessels were analyzed. Lung vessels thrombi persisted in samples of all 36 patients (100%). Vessels with the diameter 3,5-30 mm were thrombosed in 7%, with the diameter 0,034-0,84 mm - in 48%, with the diameter 0,85-3,4 mm - in 45%. The frequency of thrombi persisted 06 hours, 6-12 hours, 12-18hours, 18-24 hours and more than 24 hours was12%, 14%, 62%, 5% and 7% respectively.Conclusion. Thrombi of different ages from fresh to organized were observed in one third of lung vessels in all deceased patients. Lung vessels thrombosis plays an important role in pathogenesis and thanatogenesis of COVID-19. The D-dimer level correlates with lung, renal dysfunction, patients' mortality and doesn't show any correlation with ACT and can be accepted as a criterion of lung vessel thrombotic progression.