Background: Thrombomodulin (TM) is a transmembrane glycoprotein expressed on the endothelial cell functioning as a cofactor in the anticoagulation system. However, aside from anticoagulation, recent studies have revealed its multiple organ protective roles such as anti-inflammation, angiogenesis, and cell proliferation, which may redefine the function of TM. Although TM is predominantly expressed on placental trophoblasts, the physiological role of TM during pregnancy remains unclear. Because the understanding of TM function has drastically progressed, these new discoveries shed light on the unknown activities of placental TM. Moreover, the clinical application of recombinant TM (rTM) has opened the possibility of TM as a therapeutic target for pregnancy complications.
Objectives: Here, we comprehensively review the studies elucidating the role of TM during pregnancy from both classic and newly discovered perspectives, and seek for its potential as a therapeutic target for pregnancy complications.
Methods: Basic research using trophoblast cells and transgenic mice, as well as cohort studies of inherited TM deficiency and clinical trials of rTM were summarized, which led us to further discuss the clinical application of rTM as a novel therapeutic for pregnancy complications.
Results and conclusion: Accumulating evidence suggest the relevance of placental TM deficiency in pregnancy complications such as miscarriage, fetal growth restriction, and preeclampsia. Most importantly, promising results in animal studies and clinical trials further assure the possibility of rTM as an optimal therapeutic for such conditions. The therapeutic potential of TM raised throughout this review could drastically change the clinical approach to pregnancy complication and improve maternal outcomes.
Keywords: placental homeostasis; pregnancy; thrombomodulin; trophoblast cell.
© 2022 International Society on Thrombosis and Haemostasis.