Tissue factor-dependent pathway in severe preeclampsia revisited

Dusse, Luci Maria Sant’Ana; Godói, Lara Carvalho; Gomes, Karina Braga; Carvalho, Maria das Graças; Lwaleed, Bashir A.

doi:10.1097/mbc.0000000000000507

Cited by 7 publications

(3 citation statements)

References 31 publications

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“…These results are consistent with those of many previous trials (discussed below). The level of plasma FVII in patients with severe PE is significantly higher than that in healthy pregnant women; therefore plasma FVII levels may show high sensitivity and specificity in differentiating between PE and normal pregnancy (Dusse et al, 2016). The coagulation factor vWF is a specific marker that reflects damage of endothelial cells; thus, damaged microvascular endothelial cells in PE promote the expression of vWF.…”

Section: Discussionmentioning

confidence: 99%

Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses

Feng

Qin

et al. 2020

PeerJ

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Background Preeclampsia remains a serious disorder that puts at risk the lives of perinatal mothers and infants worldwide. This study assessed potential pathogenic mechanisms underlying preeclampsia by investigating differentially expressed proteins (DEPs) in the serum of patients with early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) compared with healthy pregnant women. Methods Blood samples were collected from four women with EOPE, four women with LOPE, and eight women with normal pregnancies, with four women providing control samples for each preeclampsia group. Serum proteins were identified by isobaric tags for relative and absolute quantitation combined with liquid chromatography–tandem mass spectrometry. Serum proteins with differences in their levels compared with control groups of at least 1.2 fold-changes and that were also statistically significantly different between the groups at P < 0.05 were further analyzed. Bioinformatics analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathway analyses, were used to determine the key proteins and signaling pathways associated with the development of PE and to determine those DEPs that differed between women with EOPE and those with LOPE. Key protein identified by mass spectrometry was verified by enzyme linked immunosorbent assay (ELISA). Results Compared with serum samples from healthy pregnant women, those from women with EOPE displayed 70 proteins that were differentially expressed with significance. Among them, 51 proteins were significantly upregulated and 19 proteins were significantly downregulated. In serum samples from women with LOPE, 24 DEPs were identified , with 10 proteins significantly upregulated and 14 proteins significantly downregulated compared with healthy pregnant women. Bioinformatics analyses indicated that DEPs in both the EOPE and LOPE groups were associated with abnormalities in the activation of the coagulation cascade and complement system as well as with lipid metabolism. In addition, 19 DEPs in the EOPE group were closely related to placental development or invasion of tumor cells. Downregulationof pregnancy-specific beta-1-glycoprotein 9 (PSG9) in the LOPE group was confirmed by ELISA. Conclusion The pathogenesis of EOPE and LOPE appeared to be associated with coagulation cascade activation, lipid metabolism, and complement activation. However, the pathogenesis of EOPE also involved processes associated with greater placental injury. This study provided several new proteins in the serum which may be valuable for clinical diagnosis of EOPE and LOPE, and offered potential mechanisms underpinning the development of these disorders.

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Section: Discussionmentioning

confidence: 99%

Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses

Feng

Qin

et al. 2020

PeerJ

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“…Predisposition to endothelial dysfunction is thought to play a central role [4] and can lead to inflammation and hemostatic abnormalities. Women with preeclampsia are in a hyper-coagulable state compared with normal pregnant women [5], and clinical features of the disease are associated with intravascular coagulation [6], which can also complicate preeclampsia. Furthermore, women with a history of preeclampsia have an increased risk of future cardiovascular disease such as ischemic heart disease, stroke, and venous thromboembolism [1,4].…”

Section: Introductionmentioning

confidence: 99%

Increased contact activated endogenous thrombin potential in pregnant women with preeclampsia

Godtfredsen,

Palarasah,

Dolleris

et al. 2023

Blood Coagulation &Amp; Fibrinolysis

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Preeclampsia is a worldwide contributor to maternal and fetal morbidity and mortality. Women with preeclampsia are in a hyper-coagulable state with increased risk of thromboembolic disease later in life compared with normal pregnant women. The contact system (CAS) in plasma can mediate thrombin generation and is an important contributor to thrombus growth, but the activation of CAS during pregnancy complicated by preeclampsia is not yet elucidated, and CAS may play a role in the pathophysiology of preeclampsia. Therefore, the aim of the study is to address thrombin generation, and in particular, the capacity of the CAS-mediated pathway in patients with preeclampsia compared with pregnant controls. One hundred and seventeen women with preeclampsia and matched controls were included. The project was registered at www.clinicaltrials.gov as NCT04825145. CAS and tissue factor induced thrombin generation, proteins C and S, antithrombin, and histidine-rich glycoprotein (HRG) were assessed. Women with preeclampsia had significantly increased CAS and tissue factor-induced endogenous thrombin potential (ETP), and HRG compared with controls, P = 0.022, P = 0.024, and P = 0.02, respectively. The concentrations of protein C and antithrombin were significantly reduced in the preeclampsia group, P = 0.024 and P < 0.0001, respectively. No significant difference in the concentration of protein S was detected, P = 0.06. This study demonstrates a significant increased CAS-induced ETP and an overall decrease of important regulators of coagulation in women with preeclampsia compared with controls. These aspects can contribute to the hyper-coagulable state characterizing preeclampsia.

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“…While the pattern of these haemostatic derangements appears to be heterogeneous and dependent on the severity of disease and the stage of pregnancy, preeclampsia appears to exacerbate pregnancy-associated hypercoagulability leading to an overall increased risk of venous thromboembolism (VTE). 2,3,31,32 The interplay between haemostatic derangements and severity of preeclampsia does not appear to represent a one-way process and increased coagulation activation, coagulation protease signalling and intra-vascular fibrin deposition likely worsen underlying vascular dysfunction and placental hypoxia thereby contributing to disease progression. 33 Among women presenting with preeclampsia, the clinical features are frequently heterogeneous with a more severe phenotype usually observed among women presenting with early-onset preeclampsia (EOP; onset before 34 weeks of gestation) in contrast to women presenting with late-onset preeclampsia (LOP; onset at 34 weeks of gestation or later).…”

Section: Introduction Preeclampsia: Pathogenesis Clinical Features Amentioning

confidence: 99%

Pathophysiology of the Venous Thromboembolism Risk in Preeclampsia

et al. 2020

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SummaryHaemostatic derangements are a hallmark of preeclampsia and appear to favour an increased risk of venous thromboembolism. However, haemorrhagic complications have also been reported. The mechanisms underlying these competing risks remain to be fully elucidated although recent work has highlighted the role of placental factors, such as extra-cellular vesicles and inflammatory mediators, in modulating these haemostatic derangements as well as driving progression of preeclampsia. Identifying affected women at risk of thrombosis and managing the competing thrombotic and haemorrhagic risks continue to be a significant clinical challenge. Derangements in blood coagulation are also implicated in the pathogenesis of preeclampsia; however, the role of antiplatelet or anticoagulant drugs in the management of this disorder remains a source of debate. Further characterisation of the underlying molecular mechanisms would likely be of major translational relevance and could provide insights into the pathogenesis of this disease as well as the associated haemostatic dysfunction.

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Tissue factor-dependent pathway in severe preeclampsia revisited

Cited by 7 publications

References 31 publications

Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses

Serum proteins differentially expressed in early- and late-onset preeclampsia assessed using iTRAQ proteomics and bioinformatics analyses

Increased contact activated endogenous thrombin potential in pregnant women with preeclampsia

Pathophysiology of the Venous Thromboembolism Risk in Preeclampsia

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