PO073 | ANALYTICAL VARIABILITY IN FIBRINOGEN TESTING REVEALING FIBRINOGEN LONGMONT: A CASE REPORT

A. Paradiso¹, S. Cmet², E. Fontanini² | ¹Dep. of Medicine, University of Udine, Udine, Italy; ²Dep. of Laboratory Medicine, Institute of Clinical Pathology, Azienda Ospedaliera Universitaria Friuli Centrale, Udine, Italy

Background. Fibrinogen plays a central role in coagulation, as it is cleaved by thrombin into fibrin, which then assembles into a stable clot through sequential steps of protofibril formation and lateral aggregation. Congenital dysfibrinogenemia is a qualitative fibrinogen disorder caused by structural abnormalities that impair coagulation, with variable clinical presentation. Diagnosis can be challenging due to potential discrepancies between assays, and management depends on the clinical phenotype. Fibrinogen Longmont is a rare congenital dysfibrinogenemia caused by a heterozygous mutation in the Bβ chain (Arg166Cys), leading to the production of structurally abnormal fibrinogen molecules linked by aberrant disulfide bonds. It is typically characterized by a discrepancy between antigenic fibrinogen levels, which may be normal, and reduced functional activity. While early fibrin formation is relatively preserved, defective lateral aggregation impairs clot structure. This variant is associated with heterogeneous clinical and laboratory findings and may be challenging to diagnose due to inconsistencies across coagulation assays.
Case report. We report the case of an adult male was referred for hematological evaluation for isolated thrombocytopenia in the setting of liver disease, with concomitantly reduced antithrombin activity. Routine coagulation tests were within normal limits, whereas Clauss fibrinogen levels were unmeasurable using a bovine thrombin reagent on an optical analyzer. In contrast, Clauss fibrinogen activity was within the normal range when measured with a human thrombin-based reagent on the electromechanical platform, while antigenic fibrinogen levels assessed by an immunoturbidimetric assay on the analyzer were also normal. These findings highlighted marked assay-dependent variability. Given the unusual discrepancy, further investigation was undertaken, raising suspicion of a congenital fibrinogen variant consistent with fibrinogen Longmont, a condition previously associated with differences between analytical methods and thrombin sources. Indeed, DNA sequencing of exon 4 of the FGB gene confirmed that the patient was heterozygous for fibrinogen Longmont, carrying a point mutation identified as FGB NM_000514.4: c.586C>T (p.Arg196Cys).
Conclusions. Fibrinogen Longmont is associated with impaired fibrin polymerization due to defective lateral aggregation, leading to the formation of a translucent clot. In our case, the discrepant fibrinogen results appear to be primarily related to differences in clot detection methods (optical versus electromechanical). The case underscores the importance of employing multiple testing approaches when fibrinogen results are incongruent. This observation highlights the impact of analytical methodology on assay performance and interpretation and supports the added value of molecular analysis, which can be crucial for establishing a definitive diagnosis when functional assays yield inconclusive or unmeasurable results.