The kinetics and interplay of thrombin inhibition by 4 plasma proteinase inhibitors.

ABSTRACT: A novel therapeutic approach for restoring hemostasis in hemophilia is to reduce antithrombin (AT) to rebalance reduced thrombin generation. In plasma, multiple inhibitors including AT, heparin cofactor II (HCII), α₂-macroglobulin (A2M), and α₁-proteinase inhibitor (A1PI) play a role in thrombin inhibition. The goal was to study the kinetics of thrombin inhibition and the roles of various inhibitors across a broad range of AT levels. Thrombin inhibition was measured at varied concentrations of AT with and without A2M, HCII, and A1PI. Reducing AT to 0 from plasma levels in the presence HCII, A2M, and A1PI, results in slower thrombin inhibition with the time required to inhibit half the thrombin increasing approximately fourfold. Computational models of thrombin inhibit

SUBMITTER: Ma A 

PROVIDER: S-EPMC12682970 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature