Thrombosis of pulmonary vasculature despite anticoagulation and thrombolysis: The findings from seven autopsies

Abstract

Background Venous thromboembolism (VTE) with the prevalence of pulmonary microcirculatory thrombosis is considered a common complication of novel coronavirus disease (COVID-19) that develops despite anticoagulation. Methods The clinical course of the disease and the autopsy findings of seven deceased patients with verified COVID-19 were analyzed. The chest computed tomography (CT) scan was routinely performed while CT pulmonary angiography and a duplex ultrasound scan (DUS) of the lower limbs were used in cases of suspected VTE. The VTE prophylaxis was administered to all patients with intermediate or therapeutic doses of low-molecular-weight heparin. The histological examination of the lung tissue and other organs was performed with particular attention paid to the pulmonary vasculature. Results Venous thromboembolism, including deep vein thrombosis in one patient and pulmonary artery thrombosis in two patients, was confirmed by imaging tests despite anticoagulation. Systemic thrombolysis was performed in two patients with putative and confirmed pulmonary embolism. An autopsy revealed the signs of acute respiratory distress syndrome in all seven patients. Abnormalities of lung vessels were found in all cases and were represented by dystrophy and necrosis in the endothelium and muscle fibers, and by infiltration by plasmatic cells, neutrophils, and lymphocytes. Multiple clots of variable maturity were observed. All those changes developed despite anticoagulation and were preserved after systemic thrombolysis. Conclusion Inflammatory and prothrombotic changes in the arterial wall in parallel with the lack of lung perfusion may cause diffuse arterial thrombosis in the lungs. This background may be responsible for the low response to systemic anticoagulation and thrombolysis in severe forms of COVID-19.

Findings and inferences from full autopsies, minimally invasive autopsies and biopsy studies in patients who died as a result of COVID19 — A systematic review

“…Others like dementia [ 23 ], Immunosuppressive medication [ 24 ], Liver steatosis, and cerebral small vessel disease [ 31 ]. Gastric carcinoma, hepatocellular carcinoma, basal cell carcinoma [ 34 ] Graft-versus-host disease following cancer [ 44 ] Bone marrow transplantation (BMT) [ 44 ], and HIV positive status [ 45 ] Lungs Gross changes observed Thrombosis and embolic phenomenon in small- and large- sized arteries [ 4 – 6 , 9 , 14 , 17 , 18 , 24 , 36 , 40 , 42 , 43 , 45 , 46 , 48 , 51 , 52 , 59 , 60 , 66 , 68 , 70 , 76 , 80 , 83 , 86 , 88 , 92 – 94 , 97 , 104 , 105 ] Pulmonary infarction, haemorrhagic infarcts [ 6 , 27 , 78 , 80 , 83 ]. Fibrosis [ 5 , 21 , 22 ].…”

“…Fibrosis [ 5 , 21 , 22 ]. ARDS [ 47 , 62 ] Microscopic/histopathological changes noted Diffuse aveolar damage – DAD [ 4 , 6 , 9 , 14 , 17 , 20 – 25 , 30 , 31 , 35 , 36 , 40 , 41 , 43 , 46 , 49 , 50 , 52 , 55 – 58 , 64 , 65 , 68 , 69 , 71 , 74 , 77 , 78 , 80 , 81 , 83 , 86 – 88 , 92 – 94 , 97 , 104 – 106 ] Exudative DAD seen within 8 days period. Advanced DAD seen after 17 days.…”

“…Thrombosis and embolic phenomenon in small- and large- sized arteries [ 4 – 6 , 9 , 14 , 17 , 18 , 24 , 36 , 40 , 42 , 43 , 45 , 46 , 48 , 51 , 52 , 59 , 60 , 66 , 68 , 70 , 76 , 80 , 83 , 86 , 88 , 92 – 94 , 97 , 104 , 105 ]…”

“…Diffuse aveolar damage – DAD [ 4 , 6 , 9 , 14 , 17 , 20 – 25 , 30 , 31 , 35 , 36 , 40 , 41 , 43 , 46 , 49 , 50 , 52 , 55 – 58 , 64 , 65 , 68 , 69 , 71 , 74 , 77 , 78 , 80 , 81 , 83 , 86 – 88 , 92 – 94 , 97 , 104 – 106 ]…”

Utility of Non-invasive Cardiac Imaging Assessment in Coronavirus Disease 2019

“…An elegant pathophysiological scheme for COVID-19-related cardiac injury has only recently been put forward (13) and outlines numerous co-existing factors: indirect myocardial injury via a cytokine storm; organ failure due to systemic inflammatory response syndrome (SIRS); oxygen supply and demand mismatch due to acute respiratory failure; cardiotoxicity from treatments; coronary thrombosis due to plaque rupture caused by shear stress; arrhythmia; and embolic complications due to SIRS. Post-mortem studies have demonstrated microthrombi within the pulmonary vasculature (14). In addition, direct myocardial injury may be caused by inflammation following direct viral entry via ACE-2 receptor binding and cellular entry.…”