An exploratory plasma-based functional assay for phenotypic characterization of fibrinolysis in dysfibrinogenemia

Background: Congenital dysfibrinogenemia exhibits heterogeneous clinical phenotypes, ranging from bleeding to thrombosis. However, conventional fibrinogen assays primarily evaluate clot formation alone. Genetic analyses are informative but do not fully explain phenotypic diversity, particularly with respect to clot formation-lysis behavior. Objectives: This study developed a novel plasma-based functional assay for exploratory characterization of integrated clot formation-lysis kinetics in congenital dysfibrinogenemia. Methods: ) and maximum fibrinolysis velocity. Normal reference intervals were established, and the assay was applied to plasma samples from 22 patients with congenital fibrinogen disorders (19 dysfibrinogenemia and 3 hypofibrinogenemia), including carriers of variants previously reported in patients with thrombosis. Results: values within the normal range. Variants without reported thrombotic association also demonstrated normal clot-lysis profiles. Conclusion: The CLySis assay provides a functional, genotype-independent approach for exploratory characterization of clot-lysis behavior in congenital dysfibrinogenemia. This assay may support future phenotypic analyses of dysfibrinogenemia, complementing conventional genetic evaluation.