Intrinsic-like blood coagulation activity in fish: Involvement of hepatocyte growth factor activator and interspecific diversity

Factor XII-independent, intrinsic pathway-like coagulation activity is broadly present across multiple fish species in an aPTT-like assay, even without identifiable factor XII orthologs.

• Why it matters: Most fish lack factor XII and other mammalian contact-system components, yet their plasma responds to negatively charged surfaces, leaving the initiator mechanism unclear.
• What they did: The study used an aPTT-like assay to detect thrombin substrate-cleaving activity across species, then applied inhibitor assays and compared activity with HGFA genomic presence, domain organization, and structural features.
• The result: Inhibitor sensitivities did not consistently support HGFA as the principal initiator, and activity did not closely track HGFA occurrence or structure, including detection in bichir despite no clear HGFA ortholog.