Hypofibrinogenemia is a congenital fibrinogen disorder characterized by a proportional decrease of functional and antigenic fibrinogen levels. Herein, we present a unique case illustrating the complex genotype–phenotype relationship in hypofibrinogenemia and the inability of low fibrinogen levels to counteract hypercoagulability.

A 77-year-old male with factor V Leiden heterozygosity experienced surgery-related deep vein thrombosis at ages 65 and 71, along with poor wound healing and postoperative hematomas. Proportionally reduced functional and antigenic fibrinogen levels revealed hypofibrinogenemia. Whole exome sequencing identified a heterozygous fibrinogen gene cluster deletion and a hemizygous variant (p.Pro265Leu, rs6054) in the fibrinogen β (FGB) gene, both of which are associated with hypofibrinogenemia. The youngest son, who has noticeably higher fibrinogen levels, shares the deletion but does not carry the hemizygous FGB variant. This suggests that the FGB variant (p.Pro265Leu) contributes to a greater reduction in fibrinogen levels.

This case suggests that the coexistence of thrombotic risk factors and potentially reduced thrombin clearance—resulting from low fibrinogen levels due to a fibrinogen gene cluster deletion and a hemizygous FGB variant—may shift the hemostatic balance toward thrombosis in a patient with moderate hypofibrinogenemia.

Ethical approval was not required for this study, in accordance with local and Danish national guidelines. The patient is aware that his clinical details are included in this paper, and written informed consent was obtained from the patient for the publication of this case report.

S.P. performed the literature review, interpreted the data, and wrote the first draft of the manuscript, and approved the final manuscript. E.B.L. supervised the recruitment of the patient, provided clinical information of the patient, and approved the final manuscript. E.A.J. also supervised the recruitment of the patient and approved the final manuscript. E.D.B. supervised the whole exome sequencing of the patient's son, interpreted the data, and approved the final manuscript. I.S.P. supervised the whole exome sequencing of the patient, interpreted the data, and approved the final manuscript. M.V.B. planned and designed the study, supervised the coagulation analyses, oversaw the literature review, interpreted the data, supervised the writing of the manuscript, and approved the final manuscript.

Received: 22 October 2024

Accepted: 03 June 2025

Article published online:
07 August 2025

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