CO-70 | CONGENITAL AFIBRINOGENEMIA: BLEEDING PHENOTYPE, THROMBOTIC COMPLICATIONS, AND LONG-TERM MANAGEMENT IN A MULTICENTER COHORT

M. Biglietto^1|2, M. Presti¹, R.C. Santoro³, I. Nichele⁴, M. Napolitano⁵, S. Pasca⁶, A. Borchiellini⁷, B. Pollio⁸, E. Zanon⁹, G. Barillari¹⁰, A. Poz¹⁰, S. Sorella¹, S. Ligia¹, R. Mormile¹, E. Baldacci¹, G. Castaman¹¹, F. Peyvandi^12|13, C. Santoro¹ | ¹Hematology, Department of Translational and Precision Medicine, Sapienza University of Rome, Italy; ²Department of Molecular Biology, Sapienza University of Rome, Italy; ³Hemostasis and Thrombosis Unit, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy; ⁴Hematology Unit, Azienda ULSS 8 Berica - San Bortolo Hospital, Vicenza, Italy; ⁵Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Italy; ⁶Coagulation Diseases Center, Transfusion Medicine Department - Azienda Sanitaria Universitaria Integrata del Trentino, Trento, Italy; ⁷Centro di Riferimento Regionale Malattie Emorragiche e Trombotiche dell'Adulto, Divisione di Ematologia, Università Città della Salute e della Scienza di Torino, Italy; ⁸SIMT Immunohematology and Transfusion Medicine Service, Diagnostic Department, A.O. Città della Salute e della Scienza, Torino, Italy; ⁹Department of Medicine, Haemophilia Centre, University Hospital of Padua, Italy; ¹⁰Center for Hemorrhagic and Thrombotic Diseases, General and University Hospital S. Maria della Misericordia, Udine, Italy; ¹¹Centre for Bleeding Disorders and Coagulation, Careggi University Hospital, Firenze, Italy; ¹²IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy; ¹³Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milano, Italy

Background and Aims. Congenital afibrinogenemia is characterized by severe bleedings and high thrombotic risk. Due to its rarity, there are no evidence-based strategies for the management of these patients. This multicentric experience aims to describe the phenotype of a cohort of afibrinogenemic patients.
Materials and Methods. Patients diagnosed with congenital afibrinogenemia as per ISTH communication (Casini A., 2018) between 1970 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), or major; surgeries were classified as major and minor based on ESA consensus (Martin D., 2020).
Results. Patients’ characteristics are summarized in Table 1. Ten patients were included, 6 females and 4 males. Median follow-up is 19 years (0.1-55). Five patients presented with a bleeding phenotype and five with a bleeding and thrombotic phenotype. The ISTH-BAT score at diagnosis was suggestive of a bleeding disorder in 8 patients, normal in 1, and not available in 1. During follow-up, ISTH-BAT score increased in 5/8 patients. All patients experienced at least one CRNM bleeding in their life, and half of them a major hemorrhage. Two patients experienced at least one venous thrombotic event, 2 an arterial one, and 1 both: 3 events occurred during fibrinogen concentrate administration. Five patients are receiving long-term anti-hemorrhagic prophylaxis, 4 with fibrinogen concentrate and 1 with fresh frozen plasma. The median age at prophylaxis start was 15 years (0.1-39) with a median duration of prophylaxis of 17 years (5-22). The reason for prophylaxis start was cerebral hemorrhage in 2 patients, hematemesis and frequent bleeding in 2, and arterial thrombosis of the left lower limb that needed amputation and lifelong dual antiplatelet prophylaxis in 1. During prophylaxis only one patient experienced bleeding diathesis, in particular epistaxis and muscular hematomas. Five patients underwent at least one major surgery: a post-traumatic splenectomy was complicated by massive portal vein thrombosis. No woman underwent pregnancy.
Conclusions. In our cohort of 10 patients, all experienced at least one CRNM bleeding, and 5 major hemorrhages occurred. Thrombotic events occurred in half of the cohort. This confirms the dual nature of the disease, with an increased bleeding and thrombotic risk. Long-term prophylaxis was frequently required and initiated at a young age, mainly following life-threatening bleeding episodes or thrombotic complications. These findings highlight the complexity of clinical management in congenital afibrinogenemia and the need for individualized therapeutic strategies.