Prekallikrein: the catalytic crossroads of inflammation and thrombosis
TL;DR
Current evidence positions prekallikrein as a promising therapeutic target that may allow selective inhibition of thromboinflammatory processes without impairing hemostasis.
Abstract
Purpose of review The contact activation pathway, historically considered dispensable for hemostasis, has re-emerged as a critical mediator of thromboinflammation. Plasma prekallikrein, through its activation to kallikrein, links coagulation, inflammation, and vascular biology. This review is timely given increasing interest in targeting the contact system to develop safer antithrombotic therapies that minimize bleeding risk. Recent findings Emerging preclinical and translational studies demonstrate that prekallikrein contributes to thrombosis, inflammation, and endothelial dysfunction, despite minimal involvement in baseline hemostasis. Animal models reveal context-dependent roles of prekallikrein in arterial and venous thrombosis, while human data confirm that prekallikrein deficiency is not associated with bleeding. Clinical success of prekallikrein inhibition in hereditary angioedema validates the therapeutic relevance of the kallikrein–kinin system. Early-phase studies and related work targeting contact pathway components, particularly factor XI, further support this pathway as a viable antithrombotic target. Summary Collectively, current evidence positions prekallikrein as a promising therapeutic target that may allow selective inhibition of thromboinflammatory processes without impairing hemostasis. Further clinical investigation is needed to define the efficacy and safety of prekallikrein-directed therapies in thrombosis and other inflammatory conditions.