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Annemette Hvas - One of the best experts on this subject based on the ideXlab platform.

  • Thrombin generation Thrombin antiThrombin Complex and proThrombin fragment f1 2 as biomarkers for hypercoagulability in cancer patients
    Thrombosis Research, 2020
    Co-Authors: Mikkel Lundbech, Andreas Engel Krag, Thomas Decker Christensen, Annemette Hvas
    Abstract:

    Abstract Background Thrombin generation, Thrombin-antiThrombin Complex (TAT) levels, and proThrombin fragment 1+2 (F1+2) have shown potential as biomarkers of thromboembolic risk. The aims were to establish reference intervals for these three biomarkers and to assess the levels in patients with localized cancer compared with healthy individuals. Methods We included 124 healthy individuals (57 females and 67 males; aged 21–66 years), 86 patients with low-stage primary lung cancer, and 57 patients with localized head and neck cancer. Thrombin generation was determined by the calibrated automated thrombogram using platelet-poor-plasma reagent containing 1 pM tissue factor and 4 μM phospholipids. TAT and F1+2 were measured using commercial enzyme-linked immunosorbent assays. Reference intervals were calculated as mean ± 1.96 × standard deviation (Thrombin generation and F1+2) or 2.5th to 97.5th percentiles (TAT). Results The reference intervals for Thrombin generation parameters were: lag time 4.4–9.4 min, peak Thrombin 46–288 nM, time-to-peak Thrombin 8–15 min, and endogenous Thrombin potential 554–1952 nM x min. The reference interval for TAT was ≤13 μg/l, and for F1+2 it was 47–320 pmol/l. Both low-stage primary lung cancer and head and neck cancer patients had significantly higher TAT (p  Conclusion Reference intervals for Thrombin generation, TAT as well as F1+2 were established. Patients with localized cancer had significantly elevated TAT and F1+2. TAT and F1+2 may hold potential for identifying hypercoagulation in cancer patients.

  • Thrombin generation, Thrombin-antiThrombin Complex, and proThrombin fragment F1+2 as biomarkers for hypercoagulability in cancer patients.
    Thrombosis Research, 2019
    Co-Authors: Mikkel Lundbech, Andreas Engel Krag, Thomas Decker Christensen, Annemette Hvas
    Abstract:

    Abstract Background Thrombin generation, Thrombin-antiThrombin Complex (TAT) levels, and proThrombin fragment 1+2 (F1+2) have shown potential as biomarkers of thromboembolic risk. The aims were to establish reference intervals for these three biomarkers and to assess the levels in patients with localized cancer compared with healthy individuals. Methods We included 124 healthy individuals (57 females and 67 males; aged 21–66 years), 86 patients with low-stage primary lung cancer, and 57 patients with localized head and neck cancer. Thrombin generation was determined by the calibrated automated thrombogram using platelet-poor-plasma reagent containing 1 pM tissue factor and 4 μM phospholipids. TAT and F1+2 were measured using commercial enzyme-linked immunosorbent assays. Reference intervals were calculated as mean ± 1.96 × standard deviation (Thrombin generation and F1+2) or 2.5th to 97.5th percentiles (TAT). Results The reference intervals for Thrombin generation parameters were: lag time 4.4–9.4 min, peak Thrombin 46–288 nM, time-to-peak Thrombin 8–15 min, and endogenous Thrombin potential 554–1952 nM x min. The reference interval for TAT was ≤13 μg/l, and for F1+2 it was 47–320 pmol/l. Both low-stage primary lung cancer and head and neck cancer patients had significantly higher TAT (p  Conclusion Reference intervals for Thrombin generation, TAT as well as F1+2 were established. Patients with localized cancer had significantly elevated TAT and F1+2. TAT and F1+2 may hold potential for identifying hypercoagulation in cancer patients.

G Pagano - One of the best experts on this subject based on the ideXlab platform.

  • proThrombin fragment 1 2 and antiThrombin iii Thrombin Complex in microalbuminuric type 2 diabetic patients
    Diabetic Medicine, 1994
    Co-Authors: Gabriella Gruden, P Cavalloperin, Renato Romagnoli, C Olivetti, D Frezet, G Pagano
    Abstract:

    : In microalbuminuria there is an increased cardiovascular risk not fully explained by the excess of conventional risk factors. To investigate whether or not microalbuminuria is associated with haemostatic abnormalities in Type 2 diabetic patients, we measured the proThrombin fragment 1 + 2, a marker of Thrombin generation, and the Thrombin-antiThrombin Complex, a marker of Thrombin neutralization. Plasma levels of proThrombin fragment 1 + 2 and Thrombin-antiThrombin Complex were assayed in 17 microalbuminuric patients (albumin excretion rate, AER 20-200 micrograms min-1) and in 17 comparable normoalbuminuric (AER < 20 micrograms min-1) Type 2 diabetic patients. Plasma proThrombin fragment 1 + 2 was significantly higher in microalbuminuric than in normoalbuminuric patients (1.09 +/- 0.06 vs 0.86 +/- 0.04 nM, p = 0.003). Individual values of F1 + 2 were above the upper limit of the normal range in 8/17 microalbuminuric and in none of the normoalbuminuric Type 2 diabetic patients. Plasma Thrombin-antiThrombin Complex values were not significantly different in the two groups and were not correlated with AER. These results suggest that microalbuminuria is associated with a prethrombotic state and a relatively defective Thrombin neutralization. Coagulation abnormalities might be part of the cardiovascular risk in microalbuminuric patients.

  • ProThrombin fragment 1 + 2 and antiThrombin III-Thrombin Complex in microalbuminuric type 2 diabetic patients.
    Diabetic Medicine, 1994
    Co-Authors: Gabriella Gruden, Renato Romagnoli, C Olivetti, D Frezet, Paolo Cavallo-perin, G Pagano
    Abstract:

    : In microalbuminuria there is an increased cardiovascular risk not fully explained by the excess of conventional risk factors. To investigate whether or not microalbuminuria is associated with haemostatic abnormalities in Type 2 diabetic patients, we measured the proThrombin fragment 1 + 2, a marker of Thrombin generation, and the Thrombin-antiThrombin Complex, a marker of Thrombin neutralization. Plasma levels of proThrombin fragment 1 + 2 and Thrombin-antiThrombin Complex were assayed in 17 microalbuminuric patients (albumin excretion rate, AER 20-200 micrograms min-1) and in 17 comparable normoalbuminuric (AER < 20 micrograms min-1) Type 2 diabetic patients. Plasma proThrombin fragment 1 + 2 was significantly higher in microalbuminuric than in normoalbuminuric patients (1.09 +/- 0.06 vs 0.86 +/- 0.04 nM, p = 0.003). Individual values of F1 + 2 were above the upper limit of the normal range in 8/17 microalbuminuric and in none of the normoalbuminuric Type 2 diabetic patients. Plasma Thrombin-antiThrombin Complex values were not significantly different in the two groups and were not correlated with AER. These results suggest that microalbuminuria is associated with a prethrombotic state and a relatively defective Thrombin neutralization. Coagulation abnormalities might be part of the cardiovascular risk in microalbuminuric patients.

Aytemiz Gurgey - One of the best experts on this subject based on the ideXlab platform.

  • Thrombin activatable fibrinolysis inhibitor activity Thrombin antiThrombin Complex and d dimer levels in preterm neonates with early respiratory distress syndrome
    American Journal of Hematology, 2008
    Co-Authors: Tugba Gursoy, Gülsevin Tekinalp, Murat Yurdakök, Osman Ozcebe, Ayşe Korkmaz, Aytemiz Gurgey
    Abstract:

    Intraalveolar fibrin deposition found in neonates with respiratory distress syndrome (RDS) is explained by the activation of the coagulation system and inefficient fibrinolysis. However, Thrombin activatable fibrinolysis inhibitor activity (TAFIa), an inhibitor of fibrinolysis, and the ratio of D-dimer to Thrombin–antiThrombin Complex (D-dimer/TAT), an index of fibrinolytic activity, have not been reported previously in neonatal RDS. Aim of this study is to evaluate the influence of plasma TAFIa levels on the fibrinolytic state in neonatal RDS. The RDS group (Group 1) consisted of 29 neonates, and 18 neonates served as the control group (Group 2). Plasma TAFIa levels and D-dimer/TAT ratios were evaluated in all neonates in the first 6 hr of life. Neonates in the RDS group were further divided into two subgroups; Group 1a consisted of 12 neonates with evidence of mild asphyxia (Apgar score at 5 min <7 and cord pH <7.26), and Group 1b consisted of 17 nonasphyxiated neonates. No significant difference was found in TAFIa levels and D-dimer/TAT ratios between Groups 1 and 2 [214% (56.2–361%) and 124.3 (4.4–3,921) in Group 1 and 201% (60.3–381%) and 147 (5.9–1,426) in Group 2]. There were negative correlations between cord pH and TAFIa levels in both groups. Increased TAFIa levels and decreased D-dimer/TAT ratios and platelet counts were detected in mildly asphyxiated neonates when compared with nonasphyxiated ones. TAFIa is not responsible for the hypofibrinolytic state reported in RDS. However, asphyxia influences TAFIa levels and increased TAFIa levels depress fibrinolysis. Am. J. Hematol., 2008. © 2007 Wiley-Liss, Inc.

  • Thrombin activatable fibrinolysis inhibitor activity, Thrombin-antiThrombin Complex and D-dimer levels in preterm neonates with early respiratory distress syndrome.
    American Journal of Hematology, 2007
    Co-Authors: Tugba Gursoy, Gülsevin Tekinalp, Murat Yurdakök, Osman Ozcebe, Ayşe Korkmaz, Aytemiz Gurgey
    Abstract:

    Intraalveolar fibrin deposition found in neonates with respiratory distress syndrome (RDS) is explained by the activation of the coagulation system and inefficient fibrinolysis. However, Thrombin activatable fibrinolysis inhibitor activity (TAFIa), an inhibitor of fibrinolysis, and the ratio of D-dimer to Thrombin–antiThrombin Complex (D-dimer/TAT), an index of fibrinolytic activity, have not been reported previously in neonatal RDS. Aim of this study is to evaluate the influence of plasma TAFIa levels on the fibrinolytic state in neonatal RDS. The RDS group (Group 1) consisted of 29 neonates, and 18 neonates served as the control group (Group 2). Plasma TAFIa levels and D-dimer/TAT ratios were evaluated in all neonates in the first 6 hr of life. Neonates in the RDS group were further divided into two subgroups; Group 1a consisted of 12 neonates with evidence of mild asphyxia (Apgar score at 5 min

Gabriella Gruden - One of the best experts on this subject based on the ideXlab platform.

  • proThrombin fragment 1 2 and antiThrombin iii Thrombin Complex in microalbuminuric type 2 diabetic patients
    Diabetic Medicine, 1994
    Co-Authors: Gabriella Gruden, P Cavalloperin, Renato Romagnoli, C Olivetti, D Frezet, G Pagano
    Abstract:

    : In microalbuminuria there is an increased cardiovascular risk not fully explained by the excess of conventional risk factors. To investigate whether or not microalbuminuria is associated with haemostatic abnormalities in Type 2 diabetic patients, we measured the proThrombin fragment 1 + 2, a marker of Thrombin generation, and the Thrombin-antiThrombin Complex, a marker of Thrombin neutralization. Plasma levels of proThrombin fragment 1 + 2 and Thrombin-antiThrombin Complex were assayed in 17 microalbuminuric patients (albumin excretion rate, AER 20-200 micrograms min-1) and in 17 comparable normoalbuminuric (AER < 20 micrograms min-1) Type 2 diabetic patients. Plasma proThrombin fragment 1 + 2 was significantly higher in microalbuminuric than in normoalbuminuric patients (1.09 +/- 0.06 vs 0.86 +/- 0.04 nM, p = 0.003). Individual values of F1 + 2 were above the upper limit of the normal range in 8/17 microalbuminuric and in none of the normoalbuminuric Type 2 diabetic patients. Plasma Thrombin-antiThrombin Complex values were not significantly different in the two groups and were not correlated with AER. These results suggest that microalbuminuria is associated with a prethrombotic state and a relatively defective Thrombin neutralization. Coagulation abnormalities might be part of the cardiovascular risk in microalbuminuric patients.

  • ProThrombin fragment 1 + 2 and antiThrombin III-Thrombin Complex in microalbuminuric type 2 diabetic patients.
    Diabetic Medicine, 1994
    Co-Authors: Gabriella Gruden, Renato Romagnoli, C Olivetti, D Frezet, Paolo Cavallo-perin, G Pagano
    Abstract:

    : In microalbuminuria there is an increased cardiovascular risk not fully explained by the excess of conventional risk factors. To investigate whether or not microalbuminuria is associated with haemostatic abnormalities in Type 2 diabetic patients, we measured the proThrombin fragment 1 + 2, a marker of Thrombin generation, and the Thrombin-antiThrombin Complex, a marker of Thrombin neutralization. Plasma levels of proThrombin fragment 1 + 2 and Thrombin-antiThrombin Complex were assayed in 17 microalbuminuric patients (albumin excretion rate, AER 20-200 micrograms min-1) and in 17 comparable normoalbuminuric (AER < 20 micrograms min-1) Type 2 diabetic patients. Plasma proThrombin fragment 1 + 2 was significantly higher in microalbuminuric than in normoalbuminuric patients (1.09 +/- 0.06 vs 0.86 +/- 0.04 nM, p = 0.003). Individual values of F1 + 2 were above the upper limit of the normal range in 8/17 microalbuminuric and in none of the normoalbuminuric Type 2 diabetic patients. Plasma Thrombin-antiThrombin Complex values were not significantly different in the two groups and were not correlated with AER. These results suggest that microalbuminuria is associated with a prethrombotic state and a relatively defective Thrombin neutralization. Coagulation abnormalities might be part of the cardiovascular risk in microalbuminuric patients.

Esteban C Gabazza - One of the best experts on this subject based on the ideXlab platform.

  • The Coagulation and Protein C Pathways in Patients with Sleep Apnea
    Lung, 2009
    Co-Authors: Takehiro Takagi, Esteban C Gabazza, John Morser, Atsushi Fujiwara, Masaki Naito, Aiko Yamaguchi, Tetsu Kobayashi, Corina N. D’alessandro-gabazza, Daniel Boveda Ruiz, Paloma Gil Bernabe
    Abstract:

    Patients with obstructive sleep apnea (OSA) have a high frequency of cardiovascular diseases and hypercoagulability is believed to be involved in the mechanism of those vascular events. We evaluated whether there is a dysfunction in the protein C anticoagulant pathway in patients with obstructive sleep apnea. Two hundred ninety-three patients were enrolled. To confirm the diagnosis of OSA, all-night polysomnography, including determination of SpO_2, was carried out. The apnea-hypopnea index (AHI) was used for judging the presence of sleep-breathing disorder. The plasma levels of the Thrombin-antiThrombin Complex were higher in patients with AHI > 5 than in those without OSA, defined as AHI  5 and those with AHI 

  • Protective role of protein C inhibitor in monocrotaline‐induced pulmonary hypertension
    Journal of Thrombosis and Haemostasis, 2006
    Co-Authors: Yoichi Nishii, Hiroki Nakahara, Takehiro Takagi, Nelson E. Bruno, Junko Maruyama, Kazuo Maruyama, Corina N. D'alessandro-gabazza, Hajime Fujimoto, Esteban C Gabazza, Tatsuya Hayashi
    Abstract:

    Summary. Background: Protein C inhibitor (PCI) plays a role in multiple biological processes including fertilization, coagulation, fibrinolysis and kinin systems. Objectives: We hypothesized that PCI participates in the pathogenesis of pulmonary hypertension. To demonstrate this, we compared the development of pulmonary hypertension in mice overexpressing PCI in the lung with wild-type (WT) mice. Pulmonary hypertension was induced by s.c. injection of 600 mg kg−1 of monocrotaline weekly for 8 weeks. Results: Right ventricular arterial pressure was significantly increased in monocrotaline-treated WT mice compared with that in monocrotaline-treated transgenic mice. Bronchoalveolar lavage fluid (BALF) levels of Thrombin–antiThrombin Complex, monocyte chemoattractant protein-1 and platelet-derived growth factor, and the plasma level of tumor necrosis factor-α were significantly increased in monocrotaline-treated WT mice as compared with monocrotaline-treated PCI transgenic mice. Increased level of PCI-Thrombin Complex was detected in BALF from monocrotaline-treated PCI transgenic mice as compared with saline-treated PCI transgenic mice. Conclusions: This study showed that increased expression of PCI in the lung is protective against monocrotaline-induced pulmonary hypertension, suggesting a potential beneficial effect of PCI for the therapy of this disease.

  • Increased Plasma Thrombin-Activatable Fibrinolysis Inhibitor Levels in Normotensive Type 2 Diabetic Patients with Microalbuminuria
    The Journal of Clinical Endocrinology and Metabolism, 2003
    Co-Authors: Yutaka Yano, Esteban C Gabazza, Nagako Kitagawa, Kohei Morioka, Hideki Urakawa, Takashi Tanaka, Akira Katsuki, Rika Araki-sasaki, Yasuko Hori, Kaname Nakatani
    Abstract:

    Hypofibrinolysis is a common finding in patients with diabetes mellitus and a risk factor for diabetic nephropathy. Recently, a new potent inhibitor of fibrinolysis, the Thrombin-activatable fibrinolysis inhibitor (TAFI), has been isolated from human plasma. The possibility that TAFI also participates in the mechanism of hypofibrinolysis has not been appraised in diabetic patients with microalbuminuria. In the present study, we investigated the plasma levels of TAFI and its relation to urinary albumin excretion in normotensive diabetic patients with normo- and microalbuminuria. Thirty-nine normotensive nonobese type 2 diabetic patients (27 with normoalbuminuria, 12 with microalbuminuria) and 20 age-matched normal subjects were enrolled in this study. The plasma level of Thrombin-antiThrombin Complex was significantly increased (22.1 ± 2.6 vs. 8.3 ± 1.0 nmol/liter; P < 0.05), whereas the d-dimer/Thrombin-antiThrombin Complex ratio was significantly decreased (15.7 ± 1.4 vs. 26.5 ± 2.2; P < 0.05), showing t...