PO128 | FROM SEVERE THROMBOSIS TO SUCCESSFUL PREGNANCIES: ORTHOTOPIC LIVER TRANSPLANTATION IN INHERITED AFIBRINOGENEMIA WITH BUDD–CHIARI SYNDROME

G. Murante^1|2|6, S. Bergonzi^1|2|6, M. Capetta^1|2|6, F. Valeri^1|2, C. Dainese^1|2, A. Valpreda⁴, R. Pastorino^1|6, F. Bocchi^1|6, R. Romagnoli⁵, S. Martini³, B. Bruno^2|6, A. Borchiellini^1|2 | ¹Regional Centre for Hemorrhagic and Thrombotic Diseases; ²Division of Hematology; ³SSD Hepatic insufficiency and Liver Transplant; ⁴Central Lab. Baldi and Riberi; ⁵General Surgery 2U - Liver Transplant Center, Molinette Hospital, AOU Città della Salute e della Scienza di Torino, Italy; ⁶Dep. of Molecular Biotechnology and Health Sciences, University of Turin, Italy

Background. Fibrinogen (FBG) is involved in the final steps of coagulation as a precursor of fibrin monomers. Inherited FBG disorders are generally classified as quantitative or qualitative. Quantitative disorders include afibrinogenemia (aFBG), which is characterized by the complete absence of FBG. aFBG is the result of homozygosity or combined heterozygosity for the causative mutations. The diagnosis is based on the measurement of FBG activity and antigen levels which define the severity of the disorder. Clinical manifestations vary from being asymptomatic to developing catastrophic life-threatening bleeds. Although the clinical phenotype is predominantly hemorrhagic, paradoxical thrombotic events have been increasingly reported, reflecting the complex pathophysiology of this condition. The main treatment for quantitative FBG disorders is FBG supplementation.
Case report. We report the case of a 30-year-old woman diagnosed with inherited aFBG during infancy following severe gingival bleeding that required treatment with fresh frozen plasma (FFP) and red blood cell (RBC) transfusions. Throughout childhood and adolescence, she experienced recurrent mucocutaneous bleeding episodes managed with on-demand replacement therapy. In adulthood, her clinical course was complicated by recurrent hemoperitoneum secondary to hemorrhagic corpus luteum rupture, requiring surgical intervention and transfusion support. Combined oral contraceptives were subsequently introduced to prevent recurrence. In January 2018, following a spontaneous haematoma of the abdominal wall treated with FFP, a CT scan revealed splenomegaly, an enlarged and distorted liver, caudate lobe hypertrophy, no visualization of the right suprahepatic vein, leading to a diagnosis of partial Budd–Chiari syndrome. In the absence of identifiable thrombophilic conditions, the event was attributed to a multifactorial prothrombotic state associated with aFBG, estrogen exposure, and repeated FFP administration. The progression to advanced chronic liver disease, with a Model for End-Stage Liver Disease (MELD) score of 30, prompted the indication for orthotopic liver transplantation (OLT). In June 2018, a chronic right subdural haematoma was incidentally discovered during a brain CT scan performed as part of pre-OLT screening. Taking into account the complex nature of the case, there was no indications for evacuation, and it was treated conservatively. Prophylaxis with HFC (4 grams, every 72 hours) was initiated with the aim of achieving a peak > 1.5 g/L. On 27 November 2018, OLT transplant was performed after infusion of 4 g 1 hour before surgery with the aim of achieving a peak > 1.5 g/L. Intraoperative management required intensive hemostatic support, including FFP, RBC transfusions, and tranexamic acid. The postoperative course was uneventful, with rapid normalization of FBG levels the same day of OLT. Thromboprophylaxis with low-molecular-weight heparin was initiated on the first postoperative day. During long-term follow-up, the patient remained free from both bleeding and thrombotic events. Notably, she successfully completed two pregnancies with favorable outcomes under appropriate antithrombotic prophylaxis, highlighting the restoration of effective hemostatic function following transplantation.
Conclusions. We report one of the few cases of inherited aFBG, complicated with Budd-Chiari syndrome successfully treated with OLT.