Preeclampsia and Long-Term Risk of Venous Thromboembolism

Abstract

ImportanceAs venous thromboembolism (VTE) remains one of the leading causes of maternal mortality, identifying women at increased risk of VTE is of great importance. Preeclampsia is a pregnancy-induced hypertensive disorder with generalized endothelial dysfunction. Some studies suggest that preeclampsia is associated with an increased risk of VTE, but much controversy exists.ObjectiveTo examine the association between preeclampsia and the risk of VTE during pregnancy, during the puerperium, and after the puerperium.Design, Setting, and ParticipantsThis observational cohort study used Danish nationwide registries to identify all eligible primiparous women who gave birth in Denmark from January 1, 1997, to December 31, 2016. The women were followed up from primiparous pregnancy to incident VTE, emigration, death, or the end of the study (December 31, 2016). Statistical analyses were carried out from January to May 2023.ExposurePreeclampsia during primiparous pregnancy.Main Outcomes and MeasureThe main outcome was incident VTE, and the secondary outcome was all-cause mortality.ResultsA total of 522 545 primiparous women (median age, 28 years [IQR, 25-31 years]) were included, and 23 330 (4.5%) received a diagnosis of preeclampsia. Women with preeclampsia were of similar age to women without preeclampsia but had a higher burden of comorbidities. During a median follow-up of 10.2 years (IQR, 5.2-15.4 years), preeclampsia was associated with a higher incidence of VTE compared with no preeclampsia (incidence rate, 448.8 [95% CI, 399.9-503.5] vs 309.6 [95% CI, 300.6-319.9] per 1000 patient-years, corresponding to an unadjusted hazard ratio [HR] of 1.45 [95% CI, 1.29-1.63] and an adjusted HR of 1.43 [95% CI, 1.27-1.61]). When stratified according to the subcategories of VTE, preeclampsia was associated with an increased rate of deep vein thrombosis (unadjusted HR, 1.51 [95% CI, 1.32-1.72] and adjusted HR, 1.49 [95% CI, 1.31-1.70]) as well as pulmonary embolism (unadjusted HR, 1.39 [95% CI, 1.09-1.76]; adjusted HR, 1.36 [95% CI, 1.08-1.73]). These findings held true in landmark analyses during pregnancy, during the puerperium, and after the puerperium.Conclusions and RelevanceThis cohort study suggests that preeclampsia was associated with a significantly increased risk of VTE during pregnancy, during the puerperium, and after the puerperium, even after thorough adjustment. Future studies should address how to improve the clinical management of women with a history of preeclampsia to prevent VTE.

Hypertensive Disorders of Pregnancy and Pre-Pregnancy Hypertension with Subsequent Incident Venous Thromboembolic Events

“…Most recently, in a nationwide cohort study in Denmark with 10.2 years median follow-up, a 43% elevated risk of VTE was observed among primiparous women with and without preeclampsia following adjustment [31]. A 2020 review by Hart et al reported a number of pregnancy-related factors that have been associated with VTE including preeclampsia (3-fold increase) [22].…”

“…History of VTE has been reported to increase the risk of preeclampsia 50% as well as other placenta-mediated pregnancy complications [23]. A biologically plausible mechanism for placenta-mediated complications including preeclampsia [24][25][26][27][28] and VTE could be thrombophilia or thrombosis [29][30][31].…”

“…Although these preventive measures result in short-term VTE risk reduction, our findings are consistent with others that demonstrate the continued association of HDP with VTE events remote from delivery, independent of pre-pregnancy hypertension in the maternal venous system. It is also possible a shared biological risk factor increases the risk of both HDP and VTE [31].…”

“…VTE history is associated with an increased risk of preeclampsia and placenta-mediated pregnancy complications [23]. Thus, a biologically plausible mechanism for placenta-mediated complications including preeclampsia [24][25][26][27][28] and VTE may be thrombophilia or thrombosis [29][30][31]. While relationships have been reported between preeclampsia and other HDP with VTE during pregnancy or postpartum by international studies [32][33][34][35], U.S. studies and evidence regarding potential differences by race/ethnicity are lacking.…”

Evaluating Thromboprophylaxis Strategies for High-Risk Pregnancy: A Current Perspective

“…This fact is useful because of the involvement of agents such as vitamin D, nuclear factor kappa B inhibitors and acetylsalicylic acid in the treatment of NETosis in preeclampsia [ 47 ]. Attention should also be paid to the fact that preeclampsia and arterial hypertension increase the risk of VTE in the course of pregnancy and the postpartum period and even in the 13 years after [ 48 , 49 ]. The aOR for the risk of VTE in these patients is 3.1 (95% CI 1.8–5.3) [ 32 ].…”