Thrombotic complications and coagulopathy frequently occur in COVID-19 (PMID: 32552865). Recently, a high incidence of venous thromboembolism was established by consecutive autopsy, with frequent deep vein thrombosis reported in 7 out of 12 COVID-19 cases; pulmonary embolism was the direct cause of death in 4 patients (33%) (PMID: 32374815). COVID-19-associated coagulopathy is characterized by increased D-dimer and fibrinogen levels, although abnormalities in prothrombin time and platelet count are initially minimal. Moreover, hyper-inflammation also induces endothelial dysfunction leading to microvascular thrombosis with further organ damage (PMID: 32348783). There are multiple connections between coagulopathy and pathways that were found to be involved in SARS-CoV-2 infections.
1) The increased level of Angiotensin II after virus infection, which indicates the renin-angiotensin system imbalance, mediates activation of different components of the coagulation cascade that leads to micro-vascular thrombosis (PMID: 24495185). 2) In the fatal COVID-19 cases significantly higher D-dimer and fibrin degradation product levels, longer prothrombin time and activated partial thromboplastin time were revealed compared to survivors on admission (PMID: 32073213).
3) The cross-talk of the SARS-CoV-2 virus with the kallikrein-kinin system and the complement cascade plays a role in the development of micro-vascular thrombosis. 4) SARS-CoV-2 spike glycoprotein was shown to co-localize with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of two Covid-19 cases and the C4d-deposits found in COVID-19 patients may be correlated with septal capillary necrosis (PMID: 32299776).
5) Inflammatory biomarkers (IL1beta, IL-6, IL8, IL-10), coagulation factors (C-reactive protein, Factor VIII, VWF, protein C) and complementation components (C4d, C5b-9) were highly up-regulated in patients with severe and fatal disease (PMID: 32504360, PMID: 32286245).
This SARS-CoV-2 coagulation pathway network has been generated in collaboration with the Covid-19 Disease map.