ArticleProceedings of the National Academy of Sciences of the United States of America2021
Kallikrein directly interacts with and activates Factor IX, resulting in thrombin generation and fibrin formation independent of Factor XI.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 64 citations in OpenAlex.
- Potential Role of Contact Pathway Factors in Catheter-Related Thrombosis: Emerging Evidence and Therapeutic Strategies.Biomolecules · 2026Review
- Screening chemical libraries for the development of oral treatments for bleeding disorders.Blood vessels, thrombosis & hemostasis · 2026Article
- Multi-Target Anticoagulant Regulation by Peptides from Medicinal Leeches: A Unique Natural Strategy against Thrombosis.Pharmaceutical research · 2026Review
- Clinical and Genetic Heterogeneity of Factor XI Deficiency: Insights from a Southern Italian Cohort.International journal of molecular sciences · 2025Article
- The expanded immunoregulatory protease network in mosquitoes is governed by gene coexpression.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Tapping Into the Natural PZ-Independent Anticoagulant Function of ZPI to Inhibit Thrombosis With Minimal Effect on Hemostasis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Factor XII Structure-Function Relationships.Seminars in thrombosis and hemostasis · 2024Review
- Bat-derived oligopeptide LE6 inhibits the contact-kinin pathway and harbors anti-thromboinflammation and stroke potential.Zoological research · 2024Article
- Plasma kallikrein supports FXII-independent thrombin generation in mouse whole blood.Blood advances · 2024Article
- Animal models of postpartum hemorrhage.Lab animal · 2024Review
- Rare Prekallikrein Deficiency Identified During Workup of Isolated Prolonged Activated Partial Thromboplastin Time.Ochsner journal · 2024Article
- Platelet factor 4 limits neutrophil extracellular trap- and cell-free DNA-induced thrombogenicity and endothelial injury.JCI insight · 2023Article
- Histidine-rich glycoprotein attenuates catheter thrombosis.Blood advances · 2023Article
- Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor.International journal of molecular sciences · 2023Article
- Circulating prekallikrein levels are correlated with lipid levels in the chinese population: a cross-sectional study.Lipids in health and disease · 2023Article
- A novel mouse whole blood thrombin generation assay sensitive to FXI- and FIX-mediated amplification of coagulation.Blood advances · 2023Article
- Targeting the contact system in a rabbit model of extracorporeal membrane oxygenation.Blood advances · 2023Article
- Factor XII contributes to thrombotic complications and vaso-occlusion in sickle cell disease.Blood · 2023Article
- A Review of Quantitative Systems Pharmacology Models of the Coagulation Cascade: Opportunities for Improved Usability.Pharmaceutics · 2023Review
- An extensively validated whole-cell biosensor for specific, sensitive and high-throughput detection of antibacterial inhibitors targeting cell-wall biosynthesis.The Journal of antimicrobial chemotherapy · 2023Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Kallikrein (PKa), generated by activation of its precursor prekallikrein (PK), plays a role in the contact activation phase of coagulation and functions in the kallikrein-kinin system to generate bradykinin. The general dogma has been that the contribution of PKa to the coagulation cascade is dependent on its action on FXII. Recently this dogma has been challenged by studies in human plasma showing thrombin generation due to PKa activity on FIX and also by murine studies showing formation of FIXa-antithrombin complexes in FXI deficient mice. In this study, we demonstrate high-affinity binding interactions between PK(a) and FIX(a) using surface plasmon resonance and show that these interactions are likely to occur under physiological conditions. Furthermore, we directly demonstrate dose- and time-dependent cleavage of FIX by PKa in a purified system by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and chromogenic assays. By using normal pooled plasma and a range of coagulation factor-deficient plasmas, we show that this action of PKa on FIX not only results in thrombin generation, but also promotes fibrin formation in the absence of FXII or FXI. Comparison of the kinetics of either FXIa- or PKa-induced activation of FIX suggest that PKa could be a significant physiological activator of FIX. Our data indicate that the coagulation cascade needs to be redefined to indicate that PKa can directly activate FIX. The circumstances that drive PKa substrate specificity remain to be determined.
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