How does COVID-19 increase clotting risk? Coronavirus Disease COVID Hematology BloodClot Clotting NatRevImmunol UBC UNC scrippsresearch umichmedicine UCIrvine nih_nhlbi
Perspective: Understanding COVID-19-associated coagulopathy. Image Credit: NIAID
Alveolar vascular dysfunction in COVID-19 Vascular endothelium acts as an antithrombotic system by secreting various molecules that prevent platelet activation and coagulation. In COVID-19, a dysregulated vascular antithrombotic system is believed to be responsible for hypercoagulation and vasculopathy, which are life-threatening conditions.
The interaction between SARS-CoV-2 and ACE2 results in reduced cell surface expression of ACE2 at the site of infection. This further leads to activation of the kallikrein-kinin system, induction of vascular permeability, fluid accumulation, and organ injury. Related StoriesThe main protease of SARS-CoV-2 contributes to neuropathology by cleaving NF-κB essential modulator in endothelial cells, leading to vascular endothelial dysfunction. Collectively, all these factors contribute to hypercoagulation, thrombosis, and brain pathologies in COVID-19 patients.
Platelet dysfunction, Hypercoagulation, and protein C dysregulation in COVID-19-related coagulopathy COVID-19 is associated with increased platelet activation and platelet-neutrophil and platelet-monocyte aggregation. While platelet-neutrophil aggregates readily attach to the blood vessel wall and release pro-thrombotic and pro-inflammatory mediators, platelet-monocyte aggregates promote hypercoagulation by increasing the expression of monocyte tissue factor.
It is becoming increasingly evident that low protein C levels are associated with severity and mortality in hospitalized COVID-19 patients. It has been observed that shedding of endothelial thrombomodulin is associated with protein C pathway dysregulation, leading to hyperinflammation and hypercoagulation.