Intracerebral hemorrhage and thrombin-induced alterations in cerebral microvessel matrix.

ABSTRACT: Four phase III clinical trials of oral direct factor Xa or thrombin inhibitors demonstrated significantly lower intracranial hemorrhage compared to warfarin in patients with nonvalvular-atrial fibrillation. This is counter-intuitive to the principle that inhibiting thrombosis should increase hemorrhagic risk. We tested the novel hypothesis that anti-thrombin activity decreases the risk of intracerebral hemorrhage by directly inhibiting thrombin-mediated degradation of cerebral microvessel basal lamina matrix, responsible for preventing hemorrhage. Collagen IV, laminin, and perlecan each contain one or more copies of the unique α-thrombin cleavage site consensus sequence. In blinded controlled experiments, α-thrombin significantly degraded each matrix protein in vitro and i

SUBMITTER: Gu YH 

PROVIDER: S-EPMC9441730 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature