Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow's triad

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.

Keywords: Antiphospholipid antibodies; Blood flow; COVID-19; Comorbidities; Cytokine storm; Endothelial dysfunction; Platelets; Pregnancy; Thrombosis; Virchow’s triad.

Fig. 1

Virchow’s triad in the thrombogenesis in COVID-19. Virchow’s triad consists of abnormal vessel wall (endotheliitis, endothelial dysfunction with loss of glycocalyx, endothelial disruption), abnormal flow (due to hyper-viscosity, immune activation, high fibrinogen, impaired microcirculation due to hypoxia and turbulent flow due to microthrombi), and hypercoagulable state (inhibition of plasminogen system due to unopposed canonical renin-angiotensin pathway, platelet dysfunction, complement activation (not shown), and hyperimmune response)