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Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow's triad
Sakir Ahmed1, Olena Zimba2, Armen Yuri Gasparyan3
1Department of Clinical Immunology and Rheumatology, Kalinga Institute of Medical Sciences (KIMS), KIIT University, Bhubaneswar, India.
Insights
Coronavirus disease 2019 (COVID-19) is a prothrombotic condition, increasing risks for both venous and arterial thromboses. Understanding COVID-19
Area of Science:
- Cardiovascular Medicine
- Hematology
- Infectious Diseases
Background:
- Coronavirus disease 2019 (COVID-19) is associated with a high incidence of thrombotic events.
- Heparin administration has demonstrated mortality benefits in COVID-19 patients, suggesting a link between coagulation and disease severity.
Purpose of the Study:
- To explore the prothrombotic nature of COVID-19 by reviewing existing evidence.
- To understand the mechanisms contributing to thrombosis in COVID-19 using Virchow's triad principles.
Main Methods:
- Review of histopathology reports and clinical case series on COVID-19-associated thromboses.
- Analysis of coagulation markers and their correlation with thrombotic risk.
- Application of Virchow's triad (endothelial dysfunction, altered blood flow, platelet abnormalities) to COVID-19 pathogenesis.
Main Results:
- COVID-19 presents as a prothrombotic disease, acting as a significant risk factor for thrombosis.
- Endothelial dysfunction, renin-angiotensin-aldosterone system (RAAS) activation, and platelet hyperreactivity are key contributors to thrombogenesis.
- Risk stratification for COVID-19 thrombosis should incorporate age, comorbidities, D-dimer levels, CT scoring, and blood cell ratios.
Conclusions:
- COVID-19-related thromboses can be explained by Virchow's triad, involving endothelial dysfunction, hypercoagulability, and altered hemodynamics.
- Current heparin therapy may be insufficient for high-risk patients, necessitating exploration of novel treatments.
- Urgent need exists for risk stratification and investigation of advanced therapies including PAI-1 antagonists and tPA, alongside RAAS-targeting and antiplatelet agents.
Abstract:
The pathogenesis of Coronavirus disease 2019 (COVID-19) is gradually being comprehended. A high number of thrombotic episodes are reported, along with the mortality benefits of heparin. COVID-19 can be viewed as a prothrombotic disease. We overviewed the available evidence to explore this possibility. We identified various histopathology reports and clinical case series reporting thromboses in COVID-19. Also, multiple coagulation markers support this. COVID-19 can be regarded as a risk factor for thrombosis. Applying the principles of Virchow's triad, we described abnormalities in the vascular endothelium, altered blood flow, and platelet function abnormalities that lead to venous and arterial thromboses in COVID-19. Endothelial dysfunction, activation of the renin-angiotensin-aldosterone system (RAAS) with the release of procoagulant plasminogen activator inhibitor (PAI-1), and hyperimmune response with activated platelets seem to be significant contributors to thrombogenesis in COVID-19. Stratifying risk of COVID-19 thromboses should be based on age, presence of comorbidities, D-dimer, CT scoring, and various blood cell ratios. Isolated heparin therapy may not be sufficient to combat thrombosis in this disease. There is an urgent need to explore newer avenues like activated protein C, PAI-1 antagonists, and tissue plasminogen activators (tPA). These should be augmented with therapies targeting RAAS, antiplatelet drugs, repurposed antiinflammatory, and antirheumatic drugs. Key Points • Venous and arterial thromboses in COVID-19 can be viewed through the prism of Virchow's triad. • Endothelial dysfunction, platelet activation, hyperviscosity, and blood flow abnormalities due to hypoxia, immune reactions, and hypercoagulability lead to thrombogenesis in COVID-19. • There is an urgent need to stratify COVID-19 patients at risk for thrombosis using age, comorbidities, D-dimer, and CT scoring. • Patients with COVID-19 at high risk for thrombosis should be put on high dose heparin therapy.
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