“New” Coagulation Inhibitors

Abstract

Blood coagulation proceeds through a series of reactions in which plasma zymogens of serine proteases are sequentially activated by limited proteolytic cleavage. Studies concerning the regulation of this process have focused on protease inhibitors that, with the exception of α2-macroglobulin, belong to the SERPIN family of protease inhibitors — for example antithrombin III, heparin cofactor II, α1-antitrypsin, Cl esterase inhibitor and plasminogen activator inhibitor 1. Recently, two “new” protease inhibitors that may regulate coagulation have been identified, and both belong to the Kunitz family of protease inhibitors. One is referred to as the lipoprotein-associated coagulation inhibitor (LACI) (Broze et al., 1987a), or extrinsic pathway inhibitor (EPI) (Rao and Rapaport, 1987). This inhibitor inactivates factor Xa directly, and in a factor Xa dependent manner also inhibits the factor VIIa/tissue factor (VIIa/TF) catalytic complex. The other inhibitor appears to represent a form of the Alzheimer β-amyloid precursor protein, is released by stimulated platelets, and inhibits factor XIa.