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Arafat A, Gennari P, Ignatov A, Tchaikovski S. Role of tissue factor pathway inhibitor in hormone-induced venous thromboembolism. Blood Coagul Fibrinolysis 2023; 34:233-238. [PMID: 37115963 DOI: 10.1097/mbc.0000000000001198] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2023]
Abstract
ABSTRACT Exposure to higher levels of steroid hormones, like that in pregnancy or during combined hormonal contraception, increases the risk of venous thromboembolism. Development of resistance to activated protein C (APC) thought to be the underlying pathomechanism of this prothrombotic state. This coagulation phenomena is largely to be explained by the hormone-induced impairment of the protein S/ tissue factor pathway inhibitor (TFPI) leading to a less efficient inactivation of factor Va and factor VIIIa by APC. APC resistance and decreased protein S/TFPI function were associated with the risk of first as well as recurrent venous thromboembolism. Preexisting disturbances in these pathways are likely to predispose to thrombosis during hormone exposure and can persist over years after the thrombosis event.Further studies are necessary to investigate the predictive value of forgoing APC resistance and decreased protein S/TFPI function or an excessive alteration in these parameters during hormone intake on the development of hormone-induced venous thromboembolism.
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Affiliation(s)
- Amina Arafat
- Department of Obstetrics and Gynecology, Otto von Guericke University Clinic, Magdeburg, Germany
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Tchaikovski SN, Thomassen MCLGD, Stickeler E, Bremme K, Rosing J. Resistance to activated protein C and impaired TFPI activity in women with previous hormone-induced venous thromboembolism. Thromb Res 2021; 207:143-149. [PMID: 34634502 DOI: 10.1016/j.thromres.2021.09.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 09/07/2021] [Accepted: 09/25/2021] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Hormonal contraception is a well-known risk factor for venous thromboembolism (VTE). APC resistance and impaired functions of protein S and TFPI are thought to play an important role in the pathogenesis of hormone-related VTE. It is unknown, whether women, who develop VTE during hormonal contraception possess a vulnerability in these pathways, making them susceptible to thrombosis. MATERIALS AND METHODS Plasma samples were obtained from 57 premenopausal women in average 15.3 years after hormone-associated VTE and from 31 healthy controls. Thrombin generation at high tissue factor (TF) in the absence and in the presence of activated protein C (APC) and at low TF without and with inhibiting anti-protein S- and anti-TFPI-antibodies was measured via calibrated automated thrombography. RESULTS Women with previous hormone-related thrombosis had higher thrombin generation at low TF, higher APC resistance, protein S- and TFPI ratios, differences: 219.9 nM IIa.min (95%CI:90.4 to 349.3); 1.88 (95%CI:0.71 to 3.05); 0.13 (95%CI:0.01 to 0.26) and 0.19 (95%CI:0.08 to 0.30), respectively. Thrombin generation at high TF without APC did not differ between the groups. Smoking decreased thrombin generation at low TF by -222.6 nM IIa.min (95%CI: -381.1 to -64.1), the APC sensitivity ratio by -2.20 (95%CI: -3.63 to -0.77) and the TFPI ratio by -0.16 (95%CI: -0.29 to -0.03), but did not influence thrombin generation at high TF. DISCUSSION We demonstrated impairment of the protein S/TFPI system and increased APC resistance in women with previous hormone-induced VTE. Smoking decreased thrombin generation at assay conditions, dependent on the function of the TFPI system.
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Affiliation(s)
- S N Tchaikovski
- University Clinic for Gynaecology and Obstetrics, RWTH Aachen, Germany; University Clinic for Gynaecology and Obstetrics, Otto von Guericke University Magdeburg, Germany.
| | - M C L G D Thomassen
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands
| | - E Stickeler
- University Clinic for Gynaecology and Obstetrics, RWTH Aachen, Germany
| | - K Bremme
- Department of Women's and Children's Health, Division of Obstetrics and Gynaecology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - J Rosing
- Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands
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Ding L, Deng F, Yu C, He WH, Xia L, Zhou M, Huang X, Lei YP, Zhou XJ, Zhu Y, Lu NH. Portosplenomesenteric vein thrombosis in patients with early-stage severe acute pancreatitis. World J Gastroenterol 2018; 24:4054-4060. [PMID: 30254409 PMCID: PMC6148429 DOI: 10.3748/wjg.v24.i35.4054] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 06/17/2018] [Accepted: 06/25/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the incidence and risk factors of portosplenomesenteric vein thrombosis (PSMVT) in the early stage of severe acute pancreatitis (SAP).
METHODS Patients with SAP in a tertiary care setting from January 2014 to December 2016 were retrospectively reviewed. All contrast-enhanced computed tomography (CT) studies were reassessed and reviewed. Clinical outcome measures were compared between SAP patients with and without PSMVT in the early stage of the disease. Univariate and multivariate logistic regression analyses were sequentially performed to assess potential risk factors for the development of PSMVT in SAP patients. A receiver operating characteristic (ROC) curve was generated for the qualifying independent risk factors.
RESULTS Twenty-five of the one hundred and forty (17.86%) SAP patients developed PSMVT 6.19 ± 2.43 d after acute pancreatitis (AP) onset. PSMVT was confirmed by contrast-enhanced CT. Multivariate stepwise logistic regression analyses showed that Balthazar’s CT severity index (CTSI) scores [odds ratio (OR): 2.742; 95% confidence interval (CI): 1.664-4.519; P = 0.000], hypoalbuminemia (serum albumin level < 25 g/L) (OR: 32.573; 95%CI: 2.711-391.353; P = 0.006) and gastrointestinal wall thickening (OR: 4.367, 95%CI: 1.218-15.658; P = 0.024) were independent risk factors for PSMVT developed in patients with SAP. The area under the ROC curve for Balthazar’s CTSI scores was 0.777 (P = 0.000), the sensitivity was 52%, and the specificity was 93% at a cut-off value of 5.5.
CONCLUSION High Balthazar’s CTSI scores, hypoalbuminemia and gastrointestinal wall thickening are independent risk factors for PSMVT developed in the early stage of SAP.
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Affiliation(s)
- Ling Ding
- Medical College of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Feng Deng
- Medical College of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Chen Yu
- Department of medical image, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Wen-Hua He
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Liang Xia
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Mi Zhou
- Medical College of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Xin Huang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Yu-Peng Lei
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Xiao-Jiang Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Yin Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Nong-Hua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
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Fei Y, Hu J, Gao K, Tu J, Wang W, Li WQ. Risk Prediction for Portal Vein Thrombosis in Acute Pancreatitis Using Radial Basis Function. Ann Vasc Surg 2017; 47:78-84. [PMID: 28943487 DOI: 10.1016/j.avsg.2017.09.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 07/30/2017] [Accepted: 09/14/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND Acute pancreatitis (AP) can induce portosplenomesenteric vein thrombosis (PVT), which may generate higher morbidity and mortality. However current diagnostic modalities for PVT are still controversial. In recent decades, artificial neural networks have been increasingly applied in medical research. The aim of this study is to predict the risk of AP-induced PVT by radial basis function (RBF) artificial neural networks (ANNs) model. METHODS A retrospective or consecutive study of 426 individuals with AP at our unit between January 1, 2011 and July 31, 2016 was conducted. All individuals were subjected to RBF ANNs. Variables included age, gender, red blood cell specific volume (Hct), prothrombin time (PT), fasting blood glucose, D-Dimer, concentration of serum calcium ([Ca2+]), triglyceride, serum amylase (AMY), acute physiology and chronic health evaluation II score, and Ranson score. All outcomes were derived after subjecting the variables to a statistical analysis. RESULTS In the RBF ANNs model, D-dimer, AMY, Hct, and PT were the important factors among all 11 independent variables for PVT. The normalized importance of them was 100%, 96.3%, 71.9%, and 68.2%, respectively. The predict sensitivity, specificity, and accuracy by RBF ANNs model for PVT were 76.2%, 92.0%, and 88.1%, respectively. There were significant differences between the RBF ANNs and logistic regression models in these parameters (95% CI: 110.9% [-0.4 to 15.8%]; 8.4% [-3.3 to 19.2%]; and 12.8% [1.6-20.7%], respectively). In addition, the area under receiver operating characteristic curves value for identifying thrombosis when using the RBF ANNs model was 0.892 ± 0.091 (95% CI: 0.805-0.951), demonstrating better overall performance than the logistic regression model (0.762 ± 0.073; 95% CI: 0.662-0.839). CONCLUSIONS The RBF ANNs model was a valuable tool in predicting the risk of PVT following AP. AMY, D-dimer, PT, and Hct were important prediction factors of approval for AP-induced PVT.
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Affiliation(s)
- Yang Fei
- Surgical Intensive Care Unit, Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jian Hu
- School of Mechanical Engineering, Nanjing University of Science and Technology, Nanjing, China
| | - Kun Gao
- Surgical Intensive Care Unit, Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jianfeng Tu
- Surgical Intensive Care Unit, Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Wei Wang
- Department of General Surgery, Bayi Hospital Affiliated Nanjing University of Chinese Medicine/ the 81st hospital of P.L.A., Nanjing, China
| | - Wei-Qin Li
- Surgical Intensive Care Unit, Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
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Fei Y, Hu J, Gao K, Tu J, Li WQ, Wang W. Predicting risk for portal vein thrombosis in acute pancreatitis patients: A comparison of radical basis function artificial neural network and logistic regression models. J Crit Care 2017; 39:115-123. [DOI: 10.1016/j.jcrc.2017.02.032] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2016] [Revised: 02/18/2017] [Accepted: 02/20/2017] [Indexed: 12/24/2022]
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Fei Y, Gao K, Hu J, Tu J, Li WQ, Wang W, Zong GQ. Predicting the incidence of portosplenomesenteric vein thrombosis in patients with acute pancreatitis using classification and regression tree algorithm. J Crit Care 2017; 39:124-130. [PMID: 28254727 DOI: 10.1016/j.jcrc.2017.02.019] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Revised: 02/03/2017] [Accepted: 02/05/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVE The accurate prediction of portosplenomesenteric vein thrombosis (PVT) in patients with acute pancreatitis(AP) is very important but may also be difficult because of our insufficient understanding of the characteristics of AP-induced PVT. The purpose of this study is to design a decision tree model that provides critical factors associated with PVT using an approach that makes use of classification and regression tree (CART) algorithm. METHODS The analysis included 353 patients with AP who were admitted between January 2011 and December 2015. CART model and logistic regression model were each applied to the same 50% of the sample to develop the predictive training models, and these models were tested on the remaining 50%. Statistical indexes were used to evaluate the value of the prediction in the 2 models. RESULTS The predicted sensitivity, specificity, positive predictive value, negative predictive value, and accuracy by CART for PVT were 78.0%, 87.2%, 64.0%, 93.2%, and 85.2%, respectively. Significant differences could be found between the CART model and the logistic regression model in these parameters. There were significant differences between the CART and logistic regression models in these parameters (P<.05). When the CART model was used to identify PVT, the area under receiver operating characteristic curve was 0.803, which demonstrated better overall properties than the logistic regression model (area under the curve=0.696) (95% confidence interval, 0.603-0.812). CONCLUSION The CART model based on serum amylase, d-dimer, Acute Physiology and Chronic Health Evaluation II, and prothrombin time is more likely to predict the occurrence of PVT induced by AP.
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Affiliation(s)
- Yang Fei
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan E Rd, Nanjing, 210002, China
| | - Kun Gao
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan E Rd, Nanjing, 210002, China
| | - Jian Hu
- School of Mechanical Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China
| | - Jianfeng Tu
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan E Rd, Nanjing, 210002, China
| | - Wei-Qin Li
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan E Rd, Nanjing, 210002, China.
| | - Wei Wang
- Department of General Surgery, Bayi Hospital Affiliated Nanjing University of Chinese Medicine/the 81st hospital of P.L.A., Nanjing, 210002, China
| | - Guang-Quan Zong
- Department of General Surgery, Bayi Hospital Affiliated Nanjing University of Chinese Medicine/the 81st hospital of P.L.A., Nanjing, 210002, China
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