Maternal Fibrinogen is Necessary for Embryonic Development

Takayuki      Iwaki; Francis   J.   Castellino

Abstract

Fibrinogen (Fg) is a precursor of fibrin, which is one of the main components of blood clots generated during the hemostatic response. Beyond its important role in hemostasis, Fg is involving in several physiologic and pathophysiologic states, such as infection, wound healing, the progression of certain types of tumors, and the severity of atherosclerosis. In addition, Fg has a critical role in maintaining pregnancy. Ovulation, fertilization, and implantation of the fertilized egg to the uterine wall can occur in afibrinogenemic women. However, all pregnancies in these patients resulted in spontaneous miscarriage. Fg supplemental therapy allows the patients to sustain the pregnancy. Mice with a total fibrinogen deficiency (FG-/-) reproduce the human experience. Despite of successes with fibrinogen supplementation, “paradoxical thrombosis” sometimes occurs, wherein supplemental therapies cause catastrophic thrombosis, such as pulmonary and mesenteric venous thrombosis. In these therapies, syncytial knots, hyaline membrane, and multiple recent infarctions with abruptio placenta were also observed. These findings indicate that the dosage regimen of Fg in afibrinogenemia-related pregnancies needs to be optimized according to other coagulation markers, such as thrombin-antithrombin complex (TAT) concentration, which represents the extent of thrombin formation. In addition, baseline thrombin assays would be helpful to predict the potential for paradoxical thrombosis during the supplemental therapy offered during pregnancy.

Keywords: fibrinogen deficiency, pregnancy, spontaneous miscarriage, embryonic development

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