Zi Wang,1,* Su Mao,2,3,* Shujie Wang,1 Wen Zhang,4 Congwei Jia,5 Tienan Zhu1 

1Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2National Clinical Research Center for Obstetric and Gynecologic Diseases, Beijing, People’s Republic of China; 3Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Tienan Zhu, Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86 010-69151200, Email zhutienan2025@163.com

Abstract: Congenital dysfibrinogenemia (CD) and antiphospholipid syndrome (APS) are two distinct thrombotic disorders that can have significant clinical implications, especially in pregnancy. CD is a rare inherited condition caused by mutations in fibrinogen genes, leading to abnormal fibrin polymerization and fibrinolysis, and causes bleeding tendencies, thrombosis and pregnancy complications. APS, an acquired autoimmune disorder, increases the risk of recurrent thrombosis and adverse pregnancy outcomes, such as miscarriages and stillbirths. This report describes a 35-year-old woman with genetically confirmed congenital dysfibrinogenemia (CD) (heterozygous FGG c.1001A>C) who subsequently developed antiphospholipid syndrome (APS). Notably, although lupus anticoagulant and β 2GP1-IgM positivity were present since 2017, APS remained undiagnosed until 2023, following her third miscarriage. In retrospect, she fulfilled the Sydney criteria with recurrent early pregnancy loss, persistent antibodies, and livedo reticularis. During her successful pregnancy in 2021, management focused exclusively on CD: fibrinogen levels were monitored (0.47– 0.98 g/L), and fibrinogen concentrate was administered during cesarean delivery due to fetal growth restriction. This resulted in a live infant birth, despite the later recognition of placental thrombosis as APS pathology. This case highlights how CD may mask the diagnosis of APS. The aunt’s uneventful pregnancy, with the same FGG mutation but no APS, confirms CD’s limited obstetric impact. The delayed APS recognition underscores the importance of reevaluating antiphospholipid status in CD patients experiencing new thrombotic or obstetric events. However, the management of combined CD and APS remains theoretical.

Keywords: congenital dysfibrinogenemia, antiphospholipid syndrome, pregnancy, thrombosis, miscarriage, livedo reticularis