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Tiphaine Raia-barjat - One of the best experts on this subject based on the ideXlab platform.
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Tissue factor Pathway Inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study
PloS one, 2017Co-Authors: Aurélie Di Bartolomeo, Céline Chauleur, Jean-christophe Gris, Céline Chapelle, Edouard Noblot, Silvy Laporte, Tiphaine Raia-barjatAbstract:Objective The study aimed to evaluate if the rate of tissue factor Pathway Inhibitor during pregnancy and following delivery could be a predictive factor for placenta-mediated adverse pregnancy outcomes in high-risk women. Methods This was a prospective multicentre cohort study of 200 patients at a high risk of occurrence or recurrence of placenta-mediated adverse pregnancy outcomes conducted between June 2008 and October 2010. Measurements of tissue factor Pathway Inhibitor resistance (normalized ratio) and tissue factor Pathway Inhibitor activity were performed for the last 72 patients at 20, 24, 28, 32, and 36 weeks of gestation and during the postpartum period. Results Overall, 15 patients presented a placenta-mediated adverse pregnancy outcome. There was no difference in normalized tissue factor Pathway Inhibitor ratios between patients with and without placenta-mediated adverse pregnancy outcomes during pregnancy and in the post-partum period. Patients with placenta-mediated adverse pregnancy outcomes had tissue factor Pathway Inhibitor activity rates that were significantly higher than those in patients without at as early as 24 weeks of gestation. The same results were observed following delivery. Conclusion Among high-risk women, the tissue factor Pathway Inhibitor activity of patients with gestational vascular complications is higher than that in other patients. Hence, these markers could augment a screening strategy that includes an analysis of angiogenic factors as well as clinical and ultrasound imaging with Doppler measurement of the uterine arteries.
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Tissue factor Pathway Inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study
PLoS ONE, 2017Co-Authors: Aurélie Di Bartolomeo, Céline Chauleur, Jean-christophe Gris, Céline Chapelle, Edouard Noblot, Silvy Laporte, Tiphaine Raia-barjatAbstract:The study aimed to evaluate if the rate of tissue factor Pathway Inhibitor during pregnancy and following delivery could be a predictive factor for placenta-mediated adverse pregnancy outcomes in high-risk women.
K Reinhart - One of the best experts on this subject based on the ideXlab platform.
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assessment of the safety of recombinant tissue factor Pathway Inhibitor in patients with severe sepsis a multicenter randomized placebo controlled single blind dose escalation study
Critical Care Medicine, 2001Co-Authors: Edward Abraham, K Reinhart, Petr Svoboda, Allan Seibert, D Olthoff, Anthony Dal R Nogare, Russell Postier, Gunter Hempelmann, Thomas Butler, E MartinAbstract:Objective To identify a safe and potentially effective recombinant tissue factor Pathway Inhibitor (rTFPI) dose for further clinical evaluation in patients with severe sepsis.Design Prospective, randomized, single-blind, placebo-controlled, dose escalation, multicenter, multinational phase II clinic
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Tissue factor Pathway Inhibitor activity in severe sepsis.
Critical Care Medicine, 2001Co-Authors: Creasey Abla A, K ReinhartAbstract:Objective: To review the preclinical and clinical evidence that provides the therapeutic rationale for recombinant human tissue factor Pathway Inhibitor (rTFPI) as a novel treatment for human sepsis. Data Sources: A summary of published English-language literature regarding preclinical studies and limited information published about three phase II clinical studies for the evaluation of rTFPI safety in sepsis patients. Data Summary: Tissue factor Pathway Inhibitor, the physiologic Inhibitor of the tissue factor Pathway, interrupts activation of coagulation at multiple steps, including tissue factor VIIa activity, Xa activity, prothrombinase complex, and thrombin generation. Recombinant human TFPI exhibits anticoagulant and anti-inflammatory activities in animal models and humans with sepsis. These activities appear to have an important therapeutic role in protecting the microvasculature from injury and preventing multiple organ failure in sepsis. Conclusions: Tissue factor Pathway Inhibitor is a potent Inhibitor of clotting in the microvasculature, which is thought to protect organs from injury. Recombinant TFPI improved survival of septic animals in multiple models. Recent phase II results suggest that rTFPI is well tolerated, and they show a trend toward reduction in 28-day all-cause mortality in rTFPI-treated patients; in addition, rTFPI demonstrated significant reduction in thrombin generation. These results suggest that a powered study is indicated to further evaluate rTFPI utility for the adjunctive management of severe sepsis.
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Tissue factor Pathway Inhibitor activity in severe sepsis.
Critical care medicine, 2001Co-Authors: A A Creasey, K ReinhartAbstract:To review the preclinical and clinical evidence that provides the therapeutic rationale for recombinant human tissue factor Pathway Inhibitor (rTFPI) as a novel treatment for human sepsis. A summary of published English-language literature regarding preclinical studies and limited information published about three phase II clinical studies for the evaluation of rTFPI safety in sepsis patients. Tissue factor Pathway Inhibitor, the physiologic Inhibitor of the tissue factor Pathway, interrupts activation of coagulation at multiple steps, including tissue factor VIIa activity, Xa activity, prothrombinase complex, and thrombin generation. Recombinant human TFPI exhibits anticoagulant and anti-inflammatory activities in animal models and humans with sepsis. These activities appear to have an important therapeutic role in protecting the microvasculature from injury and preventing multiple organ failure in sepsis. Tissue factor Pathway Inhibitor is a potent Inhibitor of clotting in the microvasculature, which is thought to protect organs from injury. Recombinant TFPI improved survival of septic animals in multiple models. Recent phase II results suggest that rTFPI is well tolerated, and they show a trend toward reduction in 28-day all-cause mortality in rTFPI-treated patients; in addition, rTFPI demonstrated significant reduction in thrombin generation. These results suggest that a powered study is indicated to further evaluate rTFPI utility for the adjunctive management of severe sepsis.
Aurélie Di Bartolomeo - One of the best experts on this subject based on the ideXlab platform.
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Tissue factor Pathway Inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study
PloS one, 2017Co-Authors: Aurélie Di Bartolomeo, Céline Chauleur, Jean-christophe Gris, Céline Chapelle, Edouard Noblot, Silvy Laporte, Tiphaine Raia-barjatAbstract:Objective The study aimed to evaluate if the rate of tissue factor Pathway Inhibitor during pregnancy and following delivery could be a predictive factor for placenta-mediated adverse pregnancy outcomes in high-risk women. Methods This was a prospective multicentre cohort study of 200 patients at a high risk of occurrence or recurrence of placenta-mediated adverse pregnancy outcomes conducted between June 2008 and October 2010. Measurements of tissue factor Pathway Inhibitor resistance (normalized ratio) and tissue factor Pathway Inhibitor activity were performed for the last 72 patients at 20, 24, 28, 32, and 36 weeks of gestation and during the postpartum period. Results Overall, 15 patients presented a placenta-mediated adverse pregnancy outcome. There was no difference in normalized tissue factor Pathway Inhibitor ratios between patients with and without placenta-mediated adverse pregnancy outcomes during pregnancy and in the post-partum period. Patients with placenta-mediated adverse pregnancy outcomes had tissue factor Pathway Inhibitor activity rates that were significantly higher than those in patients without at as early as 24 weeks of gestation. The same results were observed following delivery. Conclusion Among high-risk women, the tissue factor Pathway Inhibitor activity of patients with gestational vascular complications is higher than that in other patients. Hence, these markers could augment a screening strategy that includes an analysis of angiogenic factors as well as clinical and ultrasound imaging with Doppler measurement of the uterine arteries.
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Tissue factor Pathway Inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study
PLoS ONE, 2017Co-Authors: Aurélie Di Bartolomeo, Céline Chauleur, Jean-christophe Gris, Céline Chapelle, Edouard Noblot, Silvy Laporte, Tiphaine Raia-barjatAbstract:The study aimed to evaluate if the rate of tissue factor Pathway Inhibitor during pregnancy and following delivery could be a predictive factor for placenta-mediated adverse pregnancy outcomes in high-risk women.
Jawed Fareed - One of the best experts on this subject based on the ideXlab platform.
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Comparative tissue factor Pathway Inhibitor release potential of heparins.
Clinical and applied thrombosis hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis Hemostasis, 2005Co-Authors: Mahmut Töbü, Debra Hoppensteadt, Omer Iqbal, C. Schultz, Walter Jeske, Jawed FareedAbstract:Tissue factor Pathway Inhibitor (TFPI) is released following the administration of unfractionated heparin, low-molecular-weight heparins, defibrotide and PI-88. In this study, the comparative effects of heparin, a low-molecular-weight heparin-gammaparin and a heparin-derived oligosaccharide mixture-subeparin (C3) were studied on functional and immunologic tissue factor Pathway Inhibitor activity levels in a non-human primate (Macaca mulatta) model. The dose-dependent effect was studied following intravenous and subcutaneous administration. Following the administration of 1 mg/kg of heparin, gammaparin, and C3, the functional levels of TFPI at 5 minutes were 2.40, 2.56, and 1.08 U/mL and the corresponding TFPI immunologic levels were 4.3-, 4.0-, and 2.1-fold, increased, respectively, over the baseline value. From these results, it can be concluded that heparin and gammaparin produced similar levels of TFPI release. Hence, gammaparin and heparin have similar TFPI release potential despite their differences in molecular weight. The influence of molecular weight, charge density, and interactions with heparin cofactor II on TFPI release are also discussed.
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Tissue factor Pathway Inhibitor release induced by defibrotide and heparins.
Clinical and applied thrombosis hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis Hemostasis, 2001Co-Authors: Giuseppe Cella, Alessandra Sbarai, Giovanna Motta, Gabriella Mazzaro, Paolo Carraro, Giuseppe Maria Andreozzi, Debra Hoppensteadt, Jawed FareedAbstract:We evaluated the release of tissue factor Pathway Inhibitor (TFPI) induced by defibrotide (DF), a single-stranded, negatively charged polydeoxyribonucleotide extracted from mammalian organ. Ten nor...
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Tissue factor Pathway Inhibitor for cardiovascular disorders
Emerging Drugs, 2000Co-Authors: Brigitte Kaiser, Debra Hoppensteadt, Jawed FareedAbstract:The tissue factor (TF) Pathway of coagulation plays a decisive role for normal haemostasis as well as in the pathophysiology of various diseases. As endogenous Inhibitor of TF-mediated coagulation, the Kunitz-type proteinase Inhibitor tissue factor Pathway Inhibitor (TFPI) is an important factor in the regulation of haemostasis and the control of clotting activation. TFPI exerts its biological effects by the binding of Factor Xa (FXa) forming a TFPI/FXa complex which then, in a second step, binds to and effectively inhibits the TF/Factor VIIa (FVIIa) complex. Due to its mechanism of action TFPI causes strong anticoagulant and antithrombotic effects under experimental conditions. Furthermore, the Inhibitor was shown to be a potent antiproliferative agent both in vitro and in vivo. Based on the pathogenetic role of TF and the TF/FVIIa complex and on the effectiveness of TFPI demonstrated in preclinical studies it is assumed that TFPI might become an important drug for various clinical indications, especiall...
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Tissue Factor Pathway Inhibitor is a Potent Inhibitor of Plasmin
Clinical and Applied Thrombosis Hemostasis, 1998Co-Authors: Rainer J. Klauser, Debra Hoppensteadt, Jawed FareedAbstract:Recombinant tissue factor Pathway Inhibitor (TFPI) was found to be a potent Inhibitor of plasmin. In an amidolytic assay the inhibition constant K i was found to be 2.86 x 10-8 M. TFPI in the same concentration range also inhibited the activation of plasminogen by tissue plasminogen activator (tPA). The amidolytic activity of tPA was not inhib ited by TFPI. Other proteinases relevant to fibrinolysis such as urokinase, α-factor XIIa, and β-factor XIIa were not inhibited by TFPI. Plasma kallikrein was weakly inhibited by TFPI. When added to plasma, TFPI also prolonged the euglobulin lysis time. The interaction of TFPI with heparin and a muco polysaccharide polysulfuric ester, a heparin-like glycosamino glycan, was studied. Heparin augmented plasmin inhibition by TFPI, while mucopolysaccharide polysulfuric ester had no ef fect. Key Words: Tissue factor Pathway Inhibitor (TFPI)— Plasmin—Inhibition—Fibrinolysis.
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Pharmacological profiling of recombinant tissue factor Pathway Inhibitor.
Seminars in thrombosis and hemostasis, 1996Co-Authors: Walter Jeske, Debra Hoppensteadt, Demetra Callas, Michael Koza, Jawed FareedAbstract:Tissue factor Pathway Inhibitor (TFPI) is a Kunitz-type serine protease Inhibitor found within the vascular system that is known to be released upon heparin administration. Tissue factor Pathway Inhibitor regulates the extrinsic Pathway by inhibiting both factors VIIa and Xa. The role of TFPI in the prevention of thrombosis is currently being elucidated. These studies describe the pharmacological profile of recombinant variants of this Inhibitor that have recently been made available for study. Recombinant TFPI (rTFPI) exhibits potent anticoagulant (PT) and antiprotease actions (anti-Xa). While carboxy truncated forms of the Inhibitor were not observed to prolong the PT, potent anti-Xa effects were still noted. In a rabbit model of stasis-thrombosis, full-length rTFPI dose-dependently inhibited thrombus formation, producing a complete inhibition of thrombosis at a dose of 500 micrograms/kg. At doses that were antithrombotically effective, minor increases in blood loss were observed in a rabbit ear bleeding model. The effect of TFPI on the inhibition of platelet activation was assessed using a flow cytometric assay. Three hundred nmol/L of rTFPI were observed to block the activation of platelets by 4.5 pmol/L recombinant tissue factor. In addition to participating in the maintenance of hemostasis, rTFPI may prove to be an effective therapeutic modality for preventing thrombus formation.
Jonathan D. Marmur - One of the best experts on this subject based on the ideXlab platform.
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Evolving role of tissue factor and its Pathway Inhibitor.
Critical Care Medicine, 2002Co-Authors: Sagar N. Doshi, Jonathan D. MarmurAbstract:Objective: To review the experimental and clinical evidence of the emerging role of tissue factor in intravascular thrombosis and to examine evidence supporting the potential use of tissue factor Pathway Inhibitor as an antithrombotic therapeutic agent. Data Sources and Study Selection: A PubMed search was conducted encompassing articles in the English language relating to tissue factor and tissue factor Pathway Inhibitor in intravascular coagulation. Conclusions: Tissue factor, a membrane-bound procoagulant glycoprotein, is the initiator of the extrinsic clotting cascade, which is the predominant coagulation Pathway in vivo. The traditional view localizes tissue factor to extravascular sites, where it remains sequestered from circulating factor VII until vascular integrity is disrupted or until tissue factor expression is induced in endothelial cells or monocytes. This perspective has been challenged since the discovery of tissue factor antigen in plasma, on circulating microparticles, and on leukocytes in whole blood. Recently, the apparent role of tissue factor has expanded with the demonstration that this molecule also functions as a signaling receptor. Recombinant tissue factor Pathway Inhibitor, an analogue of the physiologic Inhibitor of tissue factor, is a potent Inhibitor of thrombus formation in experimental models. In summary, the tissue factor Pathway initiates thrombosis in vivo. In addition to its classic tissue-bound distribution, recently discovered blood-borne tissue factor may have an important procoagulant function. Despite showing promise in early human studies, a recently completed phase 3 trial of recombinant tissue factor Pathway Inhibitor in severe sepsis failed to show a reduction in the primary end point of 28-day all-cause mortality. Tissue factor Pathway Inhibitor, however, remains a plausible therapeutic agent in other conditions of increased thrombogenicity, such as acute coronary syndromes, and further studies to examine this potential are warranted.
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Evolving role of tissue factor and its Pathway Inhibitor.
Critical care medicine, 2002Co-Authors: Sagar N. Doshi, Jonathan D. MarmurAbstract:To review the experimental and clinical evidence of the emerging role of tissue factor in intravascular thrombosis and to examine evidence supporting the potential use of tissue factor Pathway Inhibitor as an antithrombotic therapeutic agent. A PubMed search was conducted encompassing articles in the English language relating to tissue factor and tissue factor Pathway Inhibitor in intravascular coagulation. Tissue factor, a membrane-bound procoagulant glycoprotein, is the initiator of the extrinsic clotting cascade, which is the predominant coagulation Pathway in vivo. The traditional view localizes tissue factor to extravascular sites, where it remains sequestered from circulating factor VII until vascular integrity is disrupted or until tissue factor expression is induced in endothelial cells or monocytes. This perspective has been challenged since the discovery of tissue factor antigen in plasma, on circulating microparticles, and on leukocytes in whole blood. Recently, the apparent role of tissue factor has expanded with the demonstration that this molecule also functions as a signaling receptor. Recombinant tissue factor Pathway Inhibitor, an analogue of the physiologic Inhibitor of tissue factor, is a potent Inhibitor of thrombus formation in experimental models. In summary, the tissue factor Pathway initiates thrombosis in vivo. In addition to its classic tissue-bound distribution, recently discovered blood-borne tissue factor may have an important procoagulant function. Despite showing promise in early human studies, a recently completed phase 3 trial of recombinant tissue factor Pathway Inhibitor in severe sepsis failed to show a reduction in the primary end point of 28-day all-cause mortality. Tissue factor Pathway Inhibitor, however, remains a plausible therapeutic agent in other conditions of increased thrombogenicity, such as acute coronary syndromes, and further studies to examine this potential are warranted.
