Plasminogen Activator Inhibitor 1 4G/5G Polymorphism and Coagulation Factor XIII Val34leu Polymorphism: Impaired Fibrinolysis and Early Pregnancy Loss (Molecular Diagnostics and Genetics‪)‬

Inherited and acquired thrombophilia can be found in more than 50% of women suffering from recurrent pregnancy loss of unknown cause (1). Thrombophilic risk factors are also frequent in women with other vascular placental pathologies, such as preeclampsia, intrauterine growth retardation, placental abruption, and late fetal loss (2-10). The common denominator for these pregnancy complications seems to be placental insufficiency (11), of which insufficient invasion of trophoblast and increased fibrin deposition are believed to be major pathologic components (12-14). For successful implantation, invasion of the cytotrophoblast to the proper depth of the uterus is crucial. It provides anchorage for the conceptus and promotes adaptation of uteroplacental circulation (13). Urokinase plasminogen activator, its receptor, and plasminogen activator inhibitor 1 (PAI-1) [5] are believed to control proteolysis and remodeling of maternal tissue during trophoblast invasion (7, 15). On the other hand, the creation of the placental basal plate matrix (Nitabuch fibrinoid) involves the deposition of fibrin into the wall of the decidual veins at sites of trophoblast invasion by intravenous activation of the maternal procoagulant cascade (16, 17). In uncomplicated pregnancies, these systems appear to be temporally and spatially strictly regulated for a well-balanced modulation of extracellular matrix and fibrin formation. In addition, intravenous blood clots (17) and increased intervillous space fibrin (18) are frequent morphologic findings in spontaneous abortion tissue, indicating a dysfunction of hemostasis. This last fact draws attention to coagulation factor XIII (FXIII), which covalently cross-links fibrin by catalyzing the introduction of [gamma]-glutamyl-[epsilon]-lysine peptide bonds between fibrin [gamma]- and [alpha]-chains (19), and PAI-1, which plays a central role in controlling the fibrinolytic system.