CO-67 | CONGENITAL DYSFIBRINOGENEMIA: BLEEDING PHENOTYPE, THROMBOTIC COMPLICATIONS, AND LONG-TERM MANAGEMENT IN A MULTICENTER COHORT

Abstract

Background and Aims. Congenital dysfibrinogenemia is a disorder caused by structural abnormalities of the fibrinogen molecule, resulting in impaired fibrinogen function. While most patients remain asymptomatic, some may present with bleeding manifestations and/or an increased risk of thrombosis. This multicenter study aims to describe the clinical phenotype of a cohort of patients with congenital dysfibrinogenemia.Materials and Methods. Patients diagnosed with congenital dysfibrinogenemia as per ISTH communication (Casini A., 2018) between 1992 and 2025 at different hemophilia centers affiliated with the Italian Association of Hemophilia Centers (AICE) were included. Bleedings were classified as per ISTH classification (Schulman S., 2005; Kaatz S., 2015) as minor, clinically relevant non-major (CRNM), and major.Results. Patients’ characteristics are summarized in Table 1. One-hundred and ten patients were included, 64 females and 46 males. Median follow-up is 4.7 years (0.1-30.1). Three patients presented with a thrombotic phenotype. The ISTH-BAT score at diagnosis was suggestive of bleeding disorder in 4 patients, normal in 89, and not available in 17. During follow-up no changes in ISTH-BAT score were observed. Thirty-two patients experienced at least one CRNM bleeding in their lives, and two patients experienced major bleedings following sleeve gastrectomy and hip replacement surgeries. Three patients experienced one venous thrombotic event and one other an arterial one. No patient received long-term anti-hemorrhagic prophylaxis. Seventy-nine subjects underwent 173 surgeries, of whom 13 were performed with antihemorrhagic prophylaxis using either tranexamic acid, fibrinogen concentrate, or fresh frozen plasma. Eight surgeries were complicated by CRNM bleedings and 2 by major bleedings. Major bleedings were managed only with red blood cell transfusions. Twenty-eight women underwent 51 pregnancies. No woman received either antithrombotic or anti-hemorrhagic prophylaxis during pregnancy. Forty-two pregnancies were carried to term. Seven miscarriages occurred, and two voluntary abortions were performed. Two patients received prophylactic enoxaparin in the puerperium, and three received anti-hemorrhagic prophylaxis at delivery: one with tranexamic acid, one with fibrinogen concentrate, and one with fresh frozen plasma. No pregnancy was complicated by hemorrhagic or thrombotic complications.Conclusions. In this cohort, dysfibrinogenemic patients showed a mild and heterogeneous clinical phenotype, with most subjects remaining asymptomatic. Pregnancy and surgical procedures were generally undertaken without complications, even in the absence of antihemorrhagic prophylaxis. Overall, these findings support a conservative and individualized management approach.