Elevated venous thromboembolism risk in preeclampsia: molecular mechanisms and clinical impact

Abstract

Venous thromboembolism (VTE) remains a leading cause of maternal death and morbidity in the developed world. Strategies for prevention of VTE in pregnancy have been the subject of recent guidelines and consensus statements. These guidelines recommend thrombosis prevention in women who have risk factors associated with an elevated VTE risk. Preeclampsia is characterized by maternal hypertension and proteinuria developing after 20 weeks gestation, complicating up to 7% of pregnancies and is associated with a massive annual morbidity and mortality burden. Women with preeclampsia have been shown to be at increased risk of VTE with studies to date suggesting that this risk may be up to 5-fold greater than the risk of pregnancy-associated VTE in the general population. Despite the fact that preeclampsia is so common and potentially devastating, our understanding of its pathogenesis and potential therapeutic strategies remain poor. In addition, the mechanisms underlying the prothrombotic phenotype in preeclampsia are also poorly characterized although a number of potential mechanisms have been postulated. Derangements of platelet and endothelial activation and impairment of endogenous anti-coagulant pathways have been reported and may contribute to the observed VTE risk. Recently, evidence for the role of neutrophil extracellular traps (NETs) and cell-free DNA in the pathogenesis of VTE has emerged and some evidence exists to suggest that this may be of relevance in preeclampsia. Future studies aimed at understanding the diagnostic and potential therapeutic relevance of this procoagulant state are likely to be of enormous clinical benefit for pregnant women affected with this potentially devastating condition.

The role of neutrophil activation in determining the outcome of pregnancy and modulation by hormones and/or cytokines

“…Pregnant women face an increased risk (four-to fivefold) for venous thrombosis [84], which is further dramatically increased by the presence of PE [85]. Evidence also suggest that the risk of venous thrombotic embolism is greatest immediately post-partum [84].…”

Risk of preeclampsia in patients with genetic predisposition to common medical conditions: a case-control study

“…For VTE, while it is clinically-recognized that women with PE are at significantly increased risk of VTE 42,62 , thrombosis is also a trait highly-associated with recurrent pregnancy loss 97,98 . Given this, women with the highest genetic risk for VTE may have a reduced rate of live births, leading to a decreased expression of all pregnancy-related phenotypes including PE.…”

“…PE is associated with a state of hypercoagulability. Specifically, fibrinogen levels are elevated in women with PE 61 and women with PE are at significantly increased risk of VTE 42,62 . Although antiphospholipid antibody syndrome is a strong clinical risk factor for PE, the only published GWAS is a small study of Japanese women 63 .…”

Epidemiologie, Risikofaktoren und Risikostratifizierung venöser Thromboembolien (VTE) in Schwangerschaft und Wochenbett

“…Gesteigerte Thrombinbildung infolge erhöhter Freisetzung tissuefactor-enthaltender Mikropartikel aus der Plazenta, systemische Endothelzellaktivierung mit gesteigerter Plättchenadhäsivität sowie die Verminderung von Gerinnungsinhibitoren führen bei der Präeklampie in Abhängigkeit vom Schweregrad zu einer im Vergleich zur physiologischen Schwangerschaft "gesteigerten" Hyperkoagulabilität, die in Verbindung mit Hämokonzentration und Mikrozirkulationsstörungen zur Thrombose prädisponieren (Übersicht bei [87]).…”