Marchi Rita, Durual Stéphane, Pecheux Océane, Neerman-Arbez Marguerite, Casini Alessandro
Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Biomaterials Laboratory, University Clinics of Dental Medicine, University of Geneva, Geneva, Switzerland.
Haemophilia. 2023 May;29(3):836-843. doi: 10.1111/hae.14754. Epub 2023 Feb 9.
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.
We investigated how the physiological changes of hemostasis throughout the pregnancy impact the hemostatic balance in a woman with hereditary mild hypofibrinogenemia.
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.
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.
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.
遗传性低纤维蛋白原血症是一种罕见的纤维蛋白原紊乱疾病,其特征是纤维蛋白原水平降低。患有低纤维蛋白原血症的孕妇有出现不良产科结局的风险,这取决于纤维蛋白原水平。
我们研究了整个孕期止血的生理变化如何影响患有遗传性轻度低纤维蛋白原血症女性的止血平衡。
通过比浊法和扫描电子显微镜分析纤维蛋白凝块特性,通过全凝块收缩测量凝块重量和红细胞滞留情况,并通过校准自动血栓图在体外评估凝血酶生成,通过TAT在体外评估凝血酶生成。
在整个孕期,纤维蛋白原水平升高,在孕晚期达到正常值(活性3.1g/L,抗原3.2g/L)。同时,纤维蛋白聚合增加,纤维蛋白溶解减少,纤维蛋白凝块网络变得更致密,纤维蛋白纤维更粗,纤维蛋白凝块重量和红细胞滞留增加,在孕晚期达到对照组值。同样,体外和体内凝血酶生成增加,在分娩时达到最大值。
在这种遗传性轻度低纤维蛋白原血症病例中,我们观察到纤维蛋白原和凝血酶生成的生理性增加。未来的研究应集中在中度和重度低纤维蛋白原血症,以评估纤维蛋白原的变化以及凝血酶生成增加对止血平衡的总体影响。