Pulmonary Vasculopathy and Thrombosis in Patients With COVID-19

Pulmonary Vasculopathy and Thrombosis in Patients With COVID-19

By: Dana Kay, DO; Sandeep Sahay, MD, FCCP; and Jean M. Elwing, MD, FCCP
Pulmonary Vascular Disease Network
Published: May 7, 2021

COVID-19 affects several organ systems through the activation of inflammatory and coagulation cascades.¹ In this COVID in Focus article, we will review the research in one of these areas: The pulmonary vascular changes and the incidence of thrombosis observed in patients with COVID-19.

Early in 2020, Ackermann et al published a short series exploring the morphologic and molecular features of pulmonary autopsy specimens from seven patients infected by SARS-CoV-2, and they compared them with lung specimens from those who died from respiratory failure associated with influenza A (H1N1) and uninfected controls. In their analysis, they noted that infected pulmonary specimens shared features of diffuse alveolar damage with infiltrating perivascular lymphocytes when compared with the uninfected controls; however, those infected with COVID-19 had distinct angiocentric features, including endothelial injury with disrupted endothelial cell membranes, widespread vascular thrombosis with microangiopathy, and occlusion of alveolar capillaries, as well as evidence of intussusceptive angiogenesis.²

Pulmonary angiopathy was further explored by Patel and colleagues in a retrospective observational analysis of 39 patients infected with SARS-CoV-2 with severe hypoxic respiratory failure. They evaluated the physiologic, hematologic, and morphologic abnormalities seen in these patients. They highlighted diffuse pulmonary angiopathy, hypercoagulability, and increased physiologic dead space in patients with severe COVID-19 pneumonia. Perfusion defects were noted on dual-energy CT scans in all patients, as well as dilated peripheral pulmonary vessels in 63% of patients. In this study, all patients with COVID-19 were noted to be hypercoagulable, as evident by higher α-angle and maximum amplitude (MA) and absent fibrinolysis (LY30 of 0%) on thromboelastography.³

Hypercoagulopathy was also evaluated by Helms et al through a prospective study of 150 hospitalized patients at two institutions with acute respiratory distress syndrome (ARDS) due to COVID-19 and compared with a historical prospective cohort of patients without COVID-19 and with ARDS. Their primary endpoint of thrombotic events noted a higher incidence of pulmonary embolism in patients with COVID-19 and ARDS when match-compared with patients without COVID-19 and with ARDS (11.7% vs 2.1%). Additionally, patients with COVID-19 and ARDS were found to have a higher incidence of continuous renal replacement circuit and ECMO centrifugal pump thrombosis despite the use of prophylactic or full anticoagulation. The authors speculated that the etiology of the hypercoagulable state involved endothelial inflammation, as identified by high levels of von Willebrand factor and factor VIII.⁴

The incidence of venous and arterial thromboembolism in critically ill patients with COVID-19 was investigated by Klok et al, who found that of 184 patients admitted to three Dutch hospitals, the cumulative incidence of thrombotic complications was 31% despite receiving chemical thromboprophylaxis. Both arterial and venous thromboembolism were reported; 27% were noted to be venous, with pulmonary emboli being the most common (n = 25), and 3.7% were noted to be arterial. The higher incidence of thrombotic events highlighted by this study supported the importance of the use of thromboprophylaxis in this population and prompted additional study on optimal dosing and duration of anticoagulant use in this high-risk group.⁵

Overall, it appears that from a pulmonary vascular perspective, patients with COVID-19 have been noted to have evidence of vasculopathy, hypercoagulability, and increased incidences of thrombotic events. These studies are limited by small enrollment numbers and, in some, by retrospective analysis, but they nevertheless suggest paths for further investigation of the acute and chronic effects of COVID-19 on the pulmonary vascular system.

References

1. Chen G, Wu D, Guo W, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620-2629.
2. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-128.
3. Patel BV, Arachchillage DJ, Ridge CA, et al. Pulmonary angiopathy in severe COVID-19: physiologic, imaging, and hematologic observations. Am J Respir Crit Care Med. 2020;202(5):690-699.
4. Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089-1098.
5. Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thrombosis Research. 2020;191:145-147.

Dana Kay, DO

• CHEST, Pulmonary Vascular Disease Network Steering Committee Fellow-in-Training
• Pulmonary Hypertension Fellow, Mayo Clinic, Rochester, MN
• Special interest and dedicated training in the field of pulmonary vascular disease

Sandeep Sahay, MD, MSc, FCCP

• CHEST, Pulmonary Vascular Disease Network Steering Committee Member
• Co-Director, Pulmonary Hypertension/Chronic Thromboembolic Pulmonary Hypertension Programs, Houston Methodist Hospital, Houston, TX
• Dedicated to patients with pulmonary hypertension and a goal of working toward advancing science focused on better treatment options and quality of life for these patients

Jean M. Elwing, MD, FCCP

• CHEST, Pulmonary Vascular Disease Network Steering Committee Chair
• Director, Pulmonary Hypertension Program Center of Comprehensive Care, and Professor of Medicine, Division of Pulmonary, Critical Care, and Sleep, University of Cincinnati
• Primary focus is clinical care, research, and education to improve the lives of patients affected by pulmonary vascular disease

Read more COVID in Focus: Perspectives on the Literature:

Operationalizing Crisis Standards of Care: The Potential Hazards of Relying on SOFA Scores for Resource Allocation

Post-COVID-19 Recovery Care: The Need for the Interprofessional Approach

Aerosolization Risks of Noninvasive Ventilation in the Era of COVID-19

Asthma and COVID-19