Enoxaparin Effect on Pregnancy Outcomes in a Patient with Elevated Plasminogen Activator Inhibitor-1

Abstract

Background. Plasminogen activator inhibitor-1 (PAI-1) inhibits tPA and creates a prothrombotic state. Gene polymorphisms of PAI-1 are associated with elevated levels and adverse pregnancy outcomes. Case. A 36-year-old gravida 6, para 1-1-3-1 with elevated prepregnancy PAI-1 levels, a history of early-onset preeclampsia with severe features superimposed on chronic hypertension, intrauterine growth restriction (IUGR), and recurrent pregnancy loss (RPL), presented with a dichorionic-diamniotic twin gestation. She was managed with aspirin and enoxaparin and delivered appropriately grown twins at 36 weeks and 3 days, due to the development of preeclampsia superimposed on chronic hypertension. She was discharged not on enoxaparin and represented with pulmonary edema on postoperative day 8. Conclusion. It is reasonable to consider testing certain patients with recurrent pregnancy loss and/or early preeclampsia with severe features for PAI-1. If levels are elevated, treatment with prophylactic enoxaparin may be beneficial. Further research is needed to determine the effect of this therapy in patients with exceedingly poor perinatal outcomes to better assess for any impact on improved outcomes.

A strong Association between Plasminogen Activator Inhibitor Type - 1 (-657 4G/5G PAI-1) and the Development of Pre-eclampsia

“…Nonetheless, subjects with the 4G allele experienced a 1.27-fold elevated risk of developing pre-eclampsia [6,79]. Similarly to our study, a meta-analysis of 18-case control studies revealed that the 4G/5G polymorphism is related to an elevated risk of pre-eclampsia, RPL, and advocated PAI-1 examination as well as anticoagulant therapy [6,77].…”

“…PAI-1 is characterized by anti brinolytic activity via inhabiting tissues PA, and hence opposing brinolysis besides enhancing a procoagulant state during pregnancy, attenuating bleeding, and improving the stability of clot. PAI-1 elevated levels in pre-eclampsia can lead to the onset of placental damage 77 [77].…”

4P-Medicine in Obstetrics: Perspectives and Opportunities

“…В метаанализе, проведенном K. Giannakou в 2018 г., включающем 1466 первичных исследований, оценивающих генетические и негенетические факторы преэклампсии, гомозиготный полиморфизм PAI-1 оказался единственным генетическим полиморфизмом, имеющим достоверные доказательства вклада в развитие преэклампсии [17]. Хотя в настоящее время ряд авторов обращают внимание не столько на наличие полиморфизма в гене PAI-1, cколько на собственно уровень ингибитора 22 активатора плазминогена 1-го типа (PAI-1) и полагают, что при его повышении следует рассматривать вопрос о назначении профилактических доз низкомолекулярных гепаринов в целях профилактики преэклампсии и невынашивания беременности [18].…”