Familial discrepancy of clinical outcomes associated with fibrinogen Dorfen: A case of huge genital hematoma after episiotomy

Abstract

This study demonstrates a case of a huge genital hematoma after delivery, associated with fibrinogen Dorfen. Fibrinogen Dorfen is the mutation of a fibrinogen-coded exon gene, which has a single heterozygous GCC → GTC transition at codon 289 of the γ gene, predicting an Ala → Val substitution. Because Ala289 plays a crucial role in maintaining the structure of the polymerization site of hole 'a' via a hydrogen bond, it is speculated that the γ 289Ala → Val substitution can change not only the fibrinogen structure, but also the function of polymerization. In our case, although the patient's gene mutation was the same as that of her mother, there was a discrepancy in the clinical outcomes. Although the precise mechanism regarding this discrepancy remains unknown, it may cause different perinatal outcomes in terms of vaginal delivery, such as the severe bleeding in this patient and the absence of clinical symptoms in her mother. This is the first report suggesting the heterogeneity of fibrinogen functions of fibrinogen Dorfen, which may be critical to the clinical outcome.

Obstetrical and postpartum complications in women with hereditary fibrinogen disorders: A systematic literature review

“…The PPH occurred mainly in the early postpartum, requiring a blood transfusion in six cases. In addition, a genital haematoma secondary to an episiotomy requiring an arterial embolization and a blood transfusion was reported in a hypodysfibrinogenaemic woman …”

Heterozygous variant fibrinogen γA289V (Kanazawa III) was confirmed as hypodysfibrinogenemia by plasma and recombinant fibrinogens

“…As reported previously, the proposita of Kanazawa III (γA289V) was a 25‐year‐old Japanese woman with abnormal uterine bleeding after normal spontaneous vaginal delivery and genital bulging around the repaired perineal incision site. The PT and APTT were 14.5 and 33.5 seconds (normal range: 10.8‐13.2 and 23.0‐38.0 seconds, respectively).…”

“…We previously identified and reported two patients with heterozygous hypodysfibrinogenemia (Kanazawa III: γA289V), based on the weak dissociation between functional and antigenic fibrinogen level (ratio: 0.76 [proposita] and 0.86 [her mother]) . To clarify the synthesis and secretion of γA289V, we established γA289V fibrinogen‐producing CHO cell lines and subjected them to ELISA and immunoblotting analysis.…”

“…CFDs are classified according to functional and antigenic fibrinogen levels as afibrinogenemia (complete absence of fibrinogen) and hypofibrinogenemia (proportional reduction of functional and antigenic levels) of quantitative disorders and dysfibrinogenemia (reduction of functional level and normal antigenic level) and hypodysfibrinogenemia (disproportional reduction of functional and antigenic levels) of qualitative disorders . We reported previously a heterozygous variant fibrinogen (γA289V; Kanazawa III) as hypodysfibrinogenemia; however, Dear et al described the same heterozygous variant (Dorfen) as hypofibrinogenemia . γA289 is located at the “D:D” interface, which plays a central role in the initial alignment of fibrin monomers into protofibrils …”

Conservative Management of Retroperitoneal Hematoma Expanded to Prerenal Space Due to Episiotomy in a Woman with Vaginal Delivery, a case report

“…Hematoma in the episiotomy site is another uncommon complication due to episiotomy [ 6 , 7 ]. Also, it could be more common and expanded in patients with underlying diseases, such as coagulation disorders [ 8 ].…”