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FGG p.Ser384Cys causes thrombin source-dependent underestimation of fibrinogen by Clauss assay: a familial case report

Year: 2026

Type: article

Abstract: Background Congenital dysfibrinogenemia is characterized by reduced functional fibrinogen despite normal antigen levels. In some variants, assay specific effects may lead to diagnostic misclassification and inappropriate clinical management. Objective To describe a thrombin source-dependent discrepancy in fibrinogen activity assays associated with the FGG p.Ser384Cys variant. Methods Three asymptomatic members of one family underwent coagulation testing, including fibrinogen activity by Clauss assays using bovine and human thrombin, fibrinogen antigen measurement, thrombin time (TT), reptilase time (RT), ROTEM SIGMA viscoelastic testing, and next generation sequencing of fibrinogen genes. Results All individuals showed markedly reduced fibrinogen activity using bovine thrombin-based Clauss assays (38-68 mg/dL) but substantially higher activity with human thrombin (101-129 mg/dL), alongside normal fibrinogen antigen levels (327-362 mg/dL). TT and RT were prolonged in all cases. ROTEM SIGMA FIBTEM clotting time and maximum clot firmness were within normal reference ranges. A heterozygous FGG c.1151C>G (p.Ser384Cys) variant was identified in all affected family members. Conclusions FGG p.Ser384Cys causes dysfibrinogenemia with selective resistance to bovine thrombin-based Clauss assays, leading to falsely low fibrinogen results despite preserved whole blood fibrin clot formation.

Source: Thrombosis Update

DOI: 10.1016/j.tru.2026.100248