Coagulopathy and COVID-19

Abstract

SARS-CoV-2 infection is associated with frequent thrombotic events, at the micro and macro-vascular level, due to the perpetuation of a state of hypercoagulability. The so-called ‘COVID-19 associated coagulopathy’ (CAC) represents a key aspect in the genesis of organ damage from SARS-CoV-2. The main coagulative alterations described in the literature are represented by high levels of D-dimer and fibrinogen. Although CAC has some common features with disseminated intravascular coagulation and sepsis-induced coagulopathy, there are important differences between these clinical pictures and the phenotype of CAC is unique. The pathogenesis of CAC is complex and is affected by the strong interconnection between the inflammatory system and coagulation, in the phenomenon of immunothrombosis and thrombo-inflammation. Several mechanisms come into play, such as inflammatory cytokines, neutrophils, the complement system as well as an alteration of the fibrinolytic system. Finally, an altered platelet function and especially endothelial dysfunction also play a central role in the pathophysiology of CAC. Heparin has several potential effects in CAC, in fact in addition to the anticoagulant effect, it could have a direct antiviral effect and anti-inflammatory properties. The high incidence of thrombo-embolic phenomena despite the use of antithrombotic prophylaxis have led some experts to recommend the use of anticoagulant doses of heparin, but at present the optimal anticoagulant regimen remains to be determined.

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

“…Coagulopathies [84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102], and especially the formation of extensive microclots in vivo, are a hallmark of both COVID [85,[103][104][105][106][107][108][109][110][111][112][113][114][115] and long COVID [116,117], and we have demonstrated that these microclots too are amyloid in character [108,109,116]. Importantly, the addition of purified, recombinant SARS-CoV-2 S1 spike protein to coagulation-competent normal plasma is sufficient to induce the formation of anomalous clots [118] that adopt amyloid states that are also resistant to fibrinolysis [108].…”

Predictive Value of Blood Coagulation Parameters in Poor Outcomes in COVID-19 Patients: A Retrospective Observational Study in Romania

“…Following SARS-CoV-2 infection, as with all infections, the human body, to defend itself, naturally triggers the innate immune system, although excessive immune responses can lead to inflammatory storms with injury to the microcirculation and activation of the coagulation system with the development of disseminated intravascular coagulation [ 6 ]. A state of hypercoagulability has been identified in cases of COVID-19, being a key aspect of micro- and macro- vascular thrombosis found in patients with this infectious disease [ 7 , 8 ]. Abnormalities of blood coagulation parameters were reported, particularly in patients with COVID-19 associated pneumonia and ARDS [ 9 ].…”

Weathering the Storm: Harnessing the Resolution of Inflammation to Limit COVID-19 Pathogenesis

“…In critically ill patients, these monocytic cells activate excessive inflammation in response to sensing PAMPs and DAMPs, which may further be exacerbated by the reduction in monocyte-originated macrophages whose role is to phagocytose the ensuing debris ( 134 , 154 , 155 ). An additional signal to trigger hyperinflammation underlying severe illness is the release of neutrophil extracellular traps (NET) and NET-stimulated coagulopathy ( 156 ). NETosis is likely initiated by both direct (through angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4 ( 157 )) and indirect (through activated platelets and COVID-19-triggered cytokines and chemokines which stimulate NETosis ( 158 )) mechanisms.…”