Thrombosis in COVID-19

Abstract

Thrombotic complications are frequent in COVID-19 and contribute significantly to mortality and morbidity. We review several mechanisms of hypercoagulability in sepsis that may be upregulated in COVID-19. These include immune-mediated thrombotic mechanisms, complement activation, macrophage activation syndrome, antiphospholipid antibody syndrome, hyperferritinemia, and renin-angiotensin system dysregulation. We highlight biomarkers within each pathway with potential prognostic value in COVID-19. Lastly, recent observational studies have evaluated a role for the expanded use of therapeutic anticoagulation in COVID-19. We review strengths and weaknesses of these studies, and we also discuss the hypothetical benefit and anticipated challenges of fibrinolytic therapy in COVID-19.

FIGURE 1:

Pulmonary emboli in the main pulmonary arteries of patients with COVID-19 (A and B). Characteristic “lines of Zahn” demonstrating alternating fibrin and erythrocyte deposition in pulmonary emboli from two patients (C and D). Reprinted from Grimes et al. with permission from the journal of Cardiovascular Pathology.

FIGURE 2:

Microscopic lung findings from patients with COVID-19. A) Diffuse alveolar damage, characteristic of acute respiratory distress syndrome, with insert showing immunohistochemistry (IHC) for fibrinogen; B) Syncitial cells, with insert showing IHC staining for thyroid transcription factor-1 that confirms pneumocyte II origin; C) Capillary congestion without diffuse alveolar damage; D) Microthrombi in alveolar capillaries, with IHC for fibrin. Reprinted from Menter et al. with permission from the journal of Histopathology.

FIGURE 3:. Components of COVID-19 Coagulopathy

Several components of the innate immune system, platelet activation, coagulation system, complement system, renin-angiotensin system, and coagulation cascade have been observed in COVID-19 or SARS. Acronyms: MASP-1, mannose binding lectin-associated serine protease; NF-Kappa-B, nuclear factor kappa B; PAI-1, plasminogen activator inhibitor 1; RAS, renin-angiotensin system; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2

CENTRAL FIGURE:. Thrombotic Pathways Implicated in COVID-19

SARS-CoV-2 infection may lead to thrombus formation via cytokine storm, macrophage activation syndrome, complement activation, platelet activation, and renin-angiotensin system dysregulation. Several of these pathways are inter-related and auto-amplifying. Acronyms: ACE2, angiotensin-converting enzyme 2; Ang II, angiotensin II, β-TG, beta thromboglobulin; IL, interleukin; MAS, macrophage activation syndrome; MASP-1, mannose binding lectin-associated serine protease; NK-cell, natural killer cell; NF-κB, nuclear factor kappa B; PAI-1, plasminogen activator inhibitor 1; PF4, platelet factor 4; ROS, reactive oxygen species; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF-α, tumor necrosis factor alpha