Editing Coagulation (section)

====Contact activation pathway (intrinsic)====
{{Anchor|Intrinsic pathway}}
The [[contact activation system|contact activation pathway]] begins with formation of the primary complex on [[collagen]] by [[high-molecular-weight kininogen]] (HMWK), [[prekallikrein]], and [[Hageman factor|FXII (Hageman factor)]]. [[Prekallikrein]] is converted to [[kallikrein]] and FXII becomes FXIIa. FXIIa converts FXI into FXIa. Factor XIa activates FIX, which with its co-factor FVIIIa form the [[tenase]] complex, which activates FX to FXa. The minor role that the contact activation pathway has in initiating blood clot formation (or more specifically, physiological [[hemostasis]]) can be illustrated by the fact that individuals with severe deficiencies of FXII, HMWK, and [[prekallikrein]] do not have a bleeding disorder. Instead, contact activation system seems to be more involved in inflammation,<ref name="Pallister1" /> and innate immunity.<ref name="Long2016">{{Cite journal |vauthors=Long AT, Kenne E, Jung R, Fuchs TA, Renné T |date=March 2016 |title=Contact system revisited: an interface between inflammation, coagulation, and innate immunity |journal=Journal of Thrombosis and Haemostasis |volume=14 |issue=3 |pages=427–37 |doi=10.1111/jth.13235 |pmid=26707513 |doi-access=free}}</ref> Interference with the pathway may confer protection against thrombosis without a significant bleeding risk.<ref name=Long2016/>

Inhibition of factor XII and PK interferes with innate immunity in animal models.<ref name=Long2016/> More promising is [[Factor XI#Inhibition|inhibition of factor XI]], which in early clinical trials have shown the expected effect.<ref>{{Cite journal |vauthors=Ruff CT, Patel SM, Giugliano RP, Morrow DA, Hug B, Kuder JF, Goodrich EL, Chen SA, Goodman SG, Joung B, Kiss RG, Spinar J, Wojakowski W, Weitz JI, Murphy SA, Wiviott SD, Parkar S, Bloomfield D, Sabatine MS |date=January 2025 |title=Abelacimab versus Rivaroxaban in Patients with Atrial Fibrillation |journal=The New England Journal of Medicine |volume=392 |issue=4 |pages=361–71 |doi=10.1056/NEJMoa2406674 |pmid=39842011}}</ref>