Low molecular weight heparin for the prevention of severe preeclampsia: where next?

Abstract

Low molecular weight heparin has been extensively evaluated for the prevention of preeclampsia in high-risk pregnant women; however, the results from these trials have been conflicting. This review discusses the potential mechanisms of action of low molecular weight heparin for the prevention of severe preeclampsia, how to optimize the selection of high-risk women for participation in future trials, and the importance of trial standardization. Preeclampsia preventionPreeclampsia is a hypertensive disorder of pregnancy, clinically diagnosed by new-onset hypertension after 20 weeks' gestation with evidence of organ injury [1]. The potential maternal and perinatal complications of preeclampsia are significant, including maternal seizures, fetal growth restriction (FGR) and stillbirth. Approximately 5% of women develop preeclampsia, with the majority of women experiencing mild preeclampsia that occurs near term and is safely managed by delivery [2]. Only 1% of pregnant women develop early-onset preeclampsia, where both the maternal and fetal implications are substantially greater, typically resulting in FGR and the need for iatrogenic preterm delivery before 34 weeks' gestation [2]. Early-onset preeclampsia is hypothesized to be a direct consequence of the interactions between a dysfunctional placenta and maternal cardiovascular system, while late-onset preeclampsia is hypothesized to be largely triggered by maternal constitutional factors [3][4][5]. Typically, women with early-onset preeclampsia present with an acute, severe syndrome that threatens the life of both the mother and her fetus. In contrast, late-onset preeclampsia is a less severe illness with a favourable clinical outcome in countries with well-developed maternity systems. However, in countries with limited medical resources, preeclampsia remains among the most frequent causes of maternal death [6].The early-and late-onset subsets of preeclampsia exhibit different types and severity of placental pathologies and express divergent maternal haemodynamics. Early-onset preeclampsia is strongly associated with placental disease characterized by maternal vascular malperfusion, where the abnormal placental villi secrete excessive amounts of antiangiogenic proteins and reduced levels of pro-angiogenic proteins into the maternal circulation [7][8][9]. Women with early-onset disease, typically associated with FGR, develop hypertension earlier in pregnancy that is characterized by increased systemic vascular resistance, reduced cardiac output and stroke volume along with relative bradycardia [5]. In contrast, late-onset preeclampsia is less commonly associated with severe placental disease, and consequently exhibits less British Journal of Clinical Pharmacology Br J Clin Pharmacol (2018) 84 673-678 673

FIGO (International Federation of Gynecology and Obstetrics) initiative on fetal growth: Best practice advice for screening, diagnosis, and management of fetal growth restriction

“…Therefore, based on the most up‐to‐date evidence, LMWH cannot be recommended for the prevention of FGR in women at high risk of placenta‐mediated complications. Its use for the prevention of FGR should therefore be limited to research settings, for example in women already on aspirin who are found to have abnormal levels of angiogenic markers prior to fetal viability 142 …”

“…Its use for the prevention of FGR should therefore be limited to research settings, for example in women already on aspirin who are found to have abnormal levels of angiogenic markers prior to fetal viability. 142…”

Heparin Use in Pregnant Women Diagnosed With Thrombophilia: Obstetric Outcomes

“…Pregnant women treated, or not, with heparin in the current study did not show differences in the frequency of preeclampsia. However, other studies have associated higher frequency of hypertensive syndromes in pregnant women with thrombophilia, as well as better fetal outcomes, with heparin treatment [20][21][22][23][24]. The small number of patients, as well as lack of knowledge about the severity of the clinical case in this subgroup (preeclampsia), may have made such evaluation difficult.…”

Preeclampsia. Eclampsia. Anesthesia and intensive care in childbirth and the puerperium. Review

“…Недопустимо планирование продленной ИВЛ на несколько суток в условиях глубокой седации, так как в этих условиях оценка состояния ЦНС без дополнительных методов исследования крайне затруднена. Не рекомендовано для профилактики ПЭ рутинное применение: режима bed-rest (дозированного постельного режима) [33], диуретиков [34], препаратов группы гепарина, в том числе низкомолекулярных гепаринов [35], хотя в последние годы появились единичные сообщения о возможной эффективности низкомолекулярных гепаринов для профилактики ПЭ [36], витаминов Е и С [37], рыбьего жира [38], чеснока [39], прогестерона [40], сульфата магния [40], фолиевой кислоты [40].…”