Physiological correction of hereditary mild hypofibrinogenemia during pregnancy

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia 2023-05, Vol.29 (3), p.836-843
• Main Authors: Marchi, Rita, Durual, Stéphane, Pecheux, Océane, Neerman‐Arbez, Marguerite, Casini, Alessandro
• Format: Article
• Language: English
• Subjects: Afibrinogenemia - genetics; Blood Coagulation; Erythrocytes; Female; Fibrin; Fibrinogen; Fibrinogen - pharmacology; fibrinogen disorders; Fibrinolysis; Hemostasis; Hemostatics - pharmacology; Humans; hypofibrinogenemia; Physiology; Pregnancy; Scanning electron microscopy; Thrombin; thrombin generation; Thrombosis
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/hae.14754

Introduction Hereditary hypofibrinogenemia is a rare fibrinogen disorder characterised by decreased levels of fibrinogen. Pregnant women with hypofibrinogenemia are at risk of adverse obstetrical outcomes, depending on the fibrinogen level. Aim We investigated how the physiological changes of hemostasis throughout the pregnancy impact the hemostatic balance in a woman with hereditary mild hypofibrinogenemia. Methods Fibrin clot properties were analyzed by turbidimetry and scanning electron microscopy, clot weight and red blood cells retention were measured by whole clot contraction, and in vitro thrombin generation was assessed by calibrated automated thrombogram and ex vivo by TAT. Results Throughout the pregnancy, the fibrinogen levels increased reaching normal values in the third trimester (activity 3.1 g/L, antigen 3.2 g/L). In parallel, the fibrin polymerisation increased, the fibrinolysis decreased, the fibrin clot network became denser with thicker fibrin fibers, and the fibrin clot weight and red blood cells retention increased, reaching control's value at the third trimester. Similarly, in vitro and ex vitro thrombin generation increased, reaching maximum values at the delivery. Conclusion In this case of hereditary mild hypofibrinogenemia we observed a physiological increase of fibrinogen and thrombin generation. Future studies should focus on moderate and severe hypofibrinogenemia, to assess fibrinogen variation and the overall impact of increased TG on the hemostasis balance.