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. 2 | OVERVIEW OF COVID-19 ASSOCIATED HYPERCOAGULOPATHY Coronavirus disease 2019 induces a prothrombotic state, and a high frequency of reported major thrombotic events raises concern for unique

Cardiac Injury Biomarkers and the Risk of Death in Patients with COVID-19: A Systematic Review and Meta-Analysis

“…Coagulopathy among COVID-19 patients is typically characterized by an elevated D-dimer concentration, prolonged prothrombin time, and a modest reduction in platelet count [ 49 ]. Multiple thrombogenic mechanisms have been proposed, such as stimulation of the complement cascade, RAS dysregulation, and thrombosis triggered by the cytokine storm [ 50 ]. Ackermann et al [ 48 ] have shown a significantly higher prevalence of alveolar capillary microthrombi and pulmonary intussusceptive angiogenesis in autopsy specimens of COVID-19 patients compared to those with influenza.…”

Clinical Characteristics, Diagnosis, and Treatment of Major Coronavirus Outbreaks

“…COVID-19 is a prothrombotic state leading to both microvascular and macrovascular thromboembolic events in pulmonary and extrapulmonary organs (136). Venous thromboembolism, particularly pulmonary embolism, is the most common coagulopathic manifestation in COVID patients (137).…”

“…Venous thromboembolism, particularly pulmonary embolism, is the most common coagulopathic manifestation in COVID patients (137). Several proposed mechanisms for thrombosis in COVID-19 patients include angiotensin-converting enzyme-2 receptor-mediated endothelial damage leading to cytokine storm, intussusceptive angiogenesis, and macrophage activation syndrome leading to activation of the coagulation cascade (136)(137)(138)(139). The incidence of thrombotic events in COVID patients is 7.7-49% in various retrospective and prospective studies (140)(141)(142)(143)(144).…”

COVID-19 and thrombosis: From bench to bedside

“…Thromboembolic complications have been reported in COVID-19 patients by different groups (just to mention few, [1] , [2] , [3] , [4] ). Importantly, various organs are affected by COVID-19 induced coagulopathy, including the vasculature of lungs [1] , legs [3] , spleen [2] , heart [5] and brain [6] .…”

“…These complications are usually associated with multiorgan failure and high mortality in severe cases of the diseases [7] . The current clinical data indicate that both pulmonary embolism (PE) and deep vein thrombosis (DVT) are the most frequently noted thrombotic events in COVID-19 [4] . Intriguingly, the risk of venous thromboembolism (VTE) remains to be high in hospitalized patients despite anticoagulation prophylaxis [8] , [9] , [10] , [12] .…”