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.