Coagulation abnormalities in COVID-19
71% of COVID-19 non-survivors had an ISTH DIC score greater than 5.32 Coagulopathy is a major complication of severe COVID-19 infections. Though highly speculative, with few studies showing concrete proof, the RAS and the coagulation pathways are intimately linked.
RAS is intimately linked to the bradykinin and coagulation pathway by ACE, which cleaves bradykinin into inactive metabolites. In vivo dimerization of the AT1 receptor and the bradykinin 2 (BK2) receptor is also known. This heterodimerization has been best studied in the context of pre-eclampsia where an augmented response to angiotensin II is seen.33 Conditions that cause heterodimerization have not been described in literature so far. It is, however, worth noting that angiotensin II binds to this receptor conformation to produce effects similar to bradykinin.
Bradykinin binds to endothelial cells causing vasodilatation and leakage of components of the coagulation pathway (kallikrein and Hageman factor) into the bloodstream. Of note, is the potential for kallikrein and Hageman factor to activate prorenin.34
Plasma renin levels positively correlate with fibrinogen, plasminogen activator inhibitor, and D-dimer levels. This correlation was not found with ACE levels.35 This further strengthens the evidence for the involvement of renin in COVID-19 pathogenesis.