المؤلفون: Michael H. Kalnoski, Hyoung Min Kang, Wayne L. Chandler, Mary Frederick

المصدر: Thrombosis Research. 115:327-340

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Antifibrinolytic, Plasmin, medicine.drug_class, medicine.medical_treatment, Models, Biological, Tissue plasminogen activator, Fibrin Fibrinogen Degradation Products, chemistry.chemical_compound, Aprotinin, Internal medicine, Plasminogen Activator Inhibitor 1, D-dimer, Fibrinolysis, medicine, Humans, Computer Simulation, Fibrinolysin, Coronary Artery Bypass, Aged, alpha-2-Antiplasmin, T-plasminogen activator, Plasminogen, Hematology, Middle Aged, Kinetics, Endocrinology, chemistry, Case-Control Studies, Tissue Plasminogen Activator, Plasminogen activator inhibitor-1, Immunology, hormones, hormone substitutes, and hormone antagonists, circulatory and respiratory physiology, medicine.drug

الوصف: Introduction The purpose of this study was to estimate, in patients undergoing cardiopulmonary bypass (CPB), the in vivo rates of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) secretion, plasmin generation, fibrin degradation, and plasmin inhibition by aprotinin versus antiplasmin. Materials and methods Estimates of in vivo rates were based on measured levels of tPA, PAI-1, antiplasmin, plasmin–antiplasmin complex (PAP), total aprotinin, plasmin–aprotinin complex and D-dimer, combined with a computer model of each patient's vascular system that continuously accounted for secretion, clearance, hemodilution, blood loss and transfusion. Plasmin regulation was studied in nine control patients undergoing CPB without aprotinin versus six patients treated with aprotinin. Results In controls, plasmin–antiplasmin levels rose from a baseline of 3.0±0.9 to a peak of 8.1±2.7 nmol/L after CPB due to an average 44-fold rise in the plasmin generation rate. This rise in plasmin generation during CPB lead to increased fibrin degradation causing D-dimer levels to increase from a baseline of 1.2±0.6 to a peak of 9.7±4.4 nmol/L due to an average 74-fold rise in the D-dimer generation rate. During CPB in the aprotinin group, plasmin–antiplasmin levels dropped, plasmin–aprotinin complex levels rose, while D-dimer levels remained unchanged from baseline. Compared to controls, the aprotinin group showed similar rates of plasmin generation during CPB, but an 11-fold faster plasmin inhibition rate and a 10-fold lower D-dimer generation rate. Conclusions The rise in plasmin generation and fibrin degradation that occurs during standard CPB is suppressed by the addition of aprotinin, which returns the patient to near baseline fibrin degradation rates during CPB.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b9f2b3a63d8cc9dca1c2dc37bd77e89Test
https://doi.org/10.1016/j.thromres.2004.09.015Test

المؤلفون: Roberta Fioriti, Antonio De Giorgi, Chiara Giannarelli, Franca Fruzzetti, Ferdinando De Negri, Giulia Dell'Omo, Franco Carmassi, Roberto Pedrinelli, Chiara Bersi

المصدر: Thrombosis Research. 116:207-214

مصطلحات موضوعية: Adult, medicine.medical_specialty, Arteriosclerosis, medicine.medical_treatment, Biology, Tissue plasminogen activator, chemistry.chemical_compound, Insulin resistance, Internal medicine, Plasminogen Activator Inhibitor 1, Fibrinolysis, medicine, Humans, Insulin, T-plasminogen activator, Hematology, medicine.disease, Polycystic ovary, Vasodilation, Endocrinology, chemistry, Case-Control Studies, Tissue Plasminogen Activator, Plasminogen activator inhibitor-1, Female, Insulin Resistance, Plasminogen activator, Blood Flow Velocity, Polycystic Ovary Syndrome, medicine.drug

الوصف: Insulin resistance, a novel cardiovascular risk factor, is often associated with increased plasminogen activator inhibitor-1 levels and impaired vasodilation. Insulin infusion in the forearm induces plasminogen activator inhibitor-1 and tissue plasminogen activator expression and endothelium-dependent vasodilation in normal subjects. The present study explores the relationship between insulin-induced vasodilatory and fibrinolytic properties of the endothelium in women with polycystic ovary syndrome, frequently affected by insulin resistance and early atherosclerosis.Metabolic, hormonal and fibrinolytic parameters were evaluated in 64 patients with polycystic ovary syndrome (19 insulin-resistant and 45 insulin-sensitive) and in 25 controls. In 16 women with polycystic ovary syndrome, 8 insulin-resistant and 8 insulin-sensitive, blood flow, plasminogen activator inhibitor-1 and tissue plasminogen activator expression were evaluated during insulin infusion into the forearm.Elevated basal plasminogen activator inhibitor-1 levels were found in women with polycystic ovary syndrome, correlating directly with insulin levels. Plasminogen activator inhibitor-1 expression increased during insulin infusion in all women with polycystic ovary syndrome, but was delayed and sustained in insulin-resistant patients (p0.01). Vasodilatory response to insulin was blunted (p0.01) and tissue plasminogen activator expression abolished in insulin-resistant patients (p0.01).Our study demonstrates that women with polycystic ovary syndrome and insulin resistance show a blunted endothelial-dependent vasodilation. The impaired endothelial release of tissue-plasminogen activator and the sustained plasminogen activator inhibitor-1 release during insulin infusion suggest a hypofibrinolytic state in PCOS patients with insulin resistance. This hemodynamic and fibrinolytic derangement may contribute to the pathogenesis of early atherosclerosis in insulin resistance.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7948b197b6a17d77e8dd00535440debeTest
https://doi.org/10.1016/j.thromres.2004.11.026Test

المؤلفون: Atilla Yalçin, Ece Akar, Nejat Akar, Erkan Yilmaz, Ferit Avcu, Şükrü Cin

المصدر: Thrombosis Research. 97:227-230

مصطلحات موضوعية: Adult, medicine.medical_specialty, Turkish population, Turkey, Deep vein, chemistry.chemical_compound, Risk Factors, Internal medicine, Plasminogen Activator Inhibitor 1, medicine, Humans, Genetic Predisposition to Disease, Risk factor, Venous Thrombosis, Polymorphism, Genetic, biology, business.industry, Factor V, Hematology, Odds ratio, medicine.disease, Thrombosis, Endocrinology, medicine.anatomical_structure, chemistry, Case-Control Studies, Plasminogen activator inhibitor-1, Mutation, Immunology, biology.protein, business, Plasminogen activator

الوصف: A decreased fibrinolytic activity due to increased levels of plasminogen activator inhibitor-1 has been shown in deep vein thrombosis patients. Elevated plasma plasminogen activator inhibitor-1 levels are associated with the 4G allele of a 4G/5G polymorphism located in the promoter region of the plasminogen activator inhibitor-1 gene. Because there is no existing data in the Turkish population, we aimed to study these mutations in patients with deep vein thrombosis ( n =136) and normal controls ( n =113), consecutively selected among unrelated healthy subjects without personal and familial history of atherothrombosis from Ankara, Turkey. DNA was extracted by conventional methods, and polymerase chain reaction of the plasminogen activator inhibitor-1 4G/5G polymorphism was performed according to a previously described method. Genotype distributions of FV 1691G-A and plasminogen activator inhibitor-1 4G/5G are as follows: plasminogen activator inhibitor-1 4G (patients) 0.562, plasminogen activator inhibitor-1 4G (controls) 0.50 ( p =0.6); FV1691A (patients) 0.147, FV1691A (controls) 0.035 ( p =0.005). Our data indicated that plasminogen activator inhibitor-1 4G/5G does not have an effect on the thrombotic risk. Carrying the 4G allele either in heterozygous or homozygous state increases the risk in the presence of FV1691A (odds ratio: 9.8 and 6.9, confidence interval 95% 2.9–32.7 and 1.3–35.8). FV1691A is an independent risk factor for thrombosis (odds ratio: 5.5, confidence interval: 95% 2.5–12.1). We concluded that coexistence of FV1691A and plasminogen activator inhibitor-1 4G allele leads to an increased risk for thrombosis leading a further evidence to another prothrombotic factor that may be necessary for the development of a manifest thrombotic event.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41cd87d4eecf48e1b035c689d0375ebaTest
https://doi.org/10.1016/s0049-3848Test(99)00164-4

المؤلفون: Emőke Pósán, Miklós Udvardy, Béla Telek, Kálmán Rák, Attila Kiss, György Ujj

المصدر: Thrombosis Research. 90:51-56

مصطلحات موضوعية: Adult, Blood Platelets, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, chemistry.chemical_compound, Polycythemia vera, Thrombin, Thromboembolism, Internal medicine, Plasminogen Activator Inhibitor 1, Fibrinolysis, medicine, Humans, Platelet, Blood Coagulation, Polycythemia Vera, Aged, Abnormal Platelet, Aged, 80 and over, Essential thrombocythemia, Hematology, Middle Aged, Platelet Activation, medicine.disease, Endocrinology, chemistry, Case-Control Studies, Plasminogen activator inhibitor-1, Immunology, Female, Plasminogen activator, Thrombocythemia, Essential, medicine.drug

الوصف: Because platelets interact with fibrinolysis in a complex manner, it can be expected that with abnormal platelet numbers and quality this interference can be even more profound. The aim of this work was to study the lysis-resistance of platelet-rich clots in diseases with high platelet counts: polycythemia vera (PV), essential thrombocythemia (ET) and to make comparison with polyglobulia (PG). Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were analyzed by an in vitro clot lysis test. Plasminogen activator inhibitor-1 (PAI-1) activity was measured in plasma and in the supernatants of the washed and gel-filtered platelets after activation by thrombin. The lysis showed decreased speed of PPP-clots in PV and ET. This phenomenon was even more marked in PRP-clots from PV and ET, but further increased lysis resistance after retraction was not observed in PV and ET, most likely due to abnormal platelet functions. Our results suggest that the fibrinolytic activity is reduced in PV and ET, and may play a role both in the increased aptitude for venous thrombosis and in the arterial complications. These are partly caused by higher plasmatic PAI-1 activity as well as by more active platelet PAI-1. The PAI-1 activity was significantly higher in the supernatants of the washed and gel-filtered platelets of PV after activation by thrombin compared with controls. Other factors might have influenced the reduced fibrinolysis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::439294e264f59cf1041ec0432d586677Test
https://doi.org/10.1016/s0049-3848Test(98)00005-x

المؤلفون: Gonul Kanigur Sultuybek, Nergiz Uçişik, Çiǧdem Bayram, Turgut Ulutin, Emine Kökoğlu, S. Süer, Hüseyin Sönmez

المصدر: Thrombosis Research. 83:77-85

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Arteriosclerosis, Cholesterol, VLDL, Coronary Disease, Biology, Pathogenesis, chemistry.chemical_compound, Internal medicine, Plasminogen Activator Inhibitor 1, Blood plasma, medicine, Humans, Triglycerides, Coronary atherosclerosis, Aged, Aged, 80 and over, Triglyceride, Cholesterol, T-plasminogen activator, Cholesterol, HDL, Cholesterol, LDL, Hematology, Lipoprotein(a), Middle Aged, medicine.disease, Endocrinology, chemistry, Case-Control Studies, Tissue Plasminogen Activator, biology.protein, Female

الوصف: In this study we investigated serum Lp(a) and plasma t-PA-PAI-1 complex levels in patients with coronary heart disease (CHD). Serum total cholesterol, triglyceride, LDL and VDL cholesterol levels (p < 0.001) and HDL cholesterol levels (p < 0.01) in patients group were found to be significantly different from those in control group. The mean Lp(a) and t-PA-PAI-1 complex levels in patients with coronary heart disease were significantly higher as compared to control group (p < 0.001). This data indicate that the elevated levels of serum Lp(a) and plasma t-PA-PAI-1 complex may play an important role in the pathogenesis of coronary atherosclerosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ffeb5f9f43b6324bc65c4e7858b61b89Test
https://doi.org/10.1016/0049-3848Test(96)00105-3

المؤلفون: Piotr Głuszko, Beata Kwasny-Krochin, Anetta Undas

المصدر: Thrombosis research. 126(1)

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Fibrinogen, Tissue plasminogen activator, Fibrin, Permeability, Fibrin Fibrinogen Degradation Products, chemistry.chemical_compound, Young Adult, Internal medicine, Fibrinolysis, Plasminogen Activator Inhibitor 1, medicine, Humans, Platelet, Blood coagulation test, Aged, Inflammation, biology, business.industry, Thrombosis, Hematology, Middle Aged, Endocrinology, chemistry, Cardiovascular Diseases, Plasminogen activator inhibitor-1, Case-Control Studies, Tissue Plasminogen Activator, Immunology, biology.protein, Female, Blood Coagulation Tests, business, Plasminogen activator, circulatory and respiratory physiology, medicine.drug

الوصف: Altered fibrin clot properties have been reported in cardiovascular diseases (CVD) and inflammatory states. Given increased prevalence of CVD in patients with rheumatoid arthritis (RA), we investigated whether fibrin characteristics are also altered in RA patients.We studied 46 consecutive RA patients versus 50 controls matched for age and gender. Ex vivo plasma clot permeability, turbidity, tissue-type plasminogen activator (tPA)-induced fibrinolysis, and scanning electron microscopy (SEM) images of clots were evaluated.Patients with RA had lower clot permeability, faster clot formation, higher maximum clot absorbency indicating thicker fibrin fibers, maximum clot mass and prolonged fibrinolysis time than controls. Maximum rates of clot lysis were similar in both groups. SEM images showed formation of dense clots with many projections on fibrin fibers. Clot permeability inversely correlated with fibrinogen, tPA, plasminogen activator inhibitor-1 (PAI-1), CRP, platelet count, disease activity score (DAS28) and a marker of oxidative stress, 8-iso-prostaglandin F2alpha (r from -0.44 to -0.79; all, p0.0001). Similar positive associations were found for clot lysis time (r 0.44 to 0.69; all, p0.01). Multiple regression analysis showed that fibrinogen was the only independent predictor of clot permeability (R2=0.87, p0.0001) and lysis time (R2=0.80, p0.003) in RA. Maximum D-dimer levels released from clots, maximum clot turbidity and the time of clot formation were predicted by PAI-1 (all, p0.05).We showed unfavorably altered plasma fibrin clot structure and function in RA, which might contribute to an increased risk of thrombotic events in this disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07f75608be239dac724559875e6ebf22Test
https://pubmed.ncbi.nlm.nih.gov/20471669Test

المؤلفون: Michal Mysliwiec, Krystyna Pawlak, Dariusz Pawlak

المصدر: Thrombosis research. 125(2)

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Kynurenine pathway, Plasmin, Kynurenic Acid, Receptors, Urokinase Plasminogen Activator, Thromboplastin, chemistry.chemical_compound, Tissue factor pathway inhibitor, Peritoneal Dialysis, Continuous Ambulatory, Internal medicine, Diabetes mellitus, Plasminogen Activator Inhibitor 1, Prevalence, Medicine, Humans, Fibrinolysin, Kynurenine, Hemostasis, business.industry, Tryptophan, Hematology, Fasting, Middle Aged, Quinolinic Acid, medicine.disease, Urokinase-Type Plasminogen Activator, Antifibrinolytic Agents, Peptide Fragments, Endocrinology, Cross-Sectional Studies, SuPAR, chemistry, Cardiovascular Diseases, Plasminogen activator inhibitor-1, Case-Control Studies, Female, Prothrombin, Poland, business, Plasminogen activator, medicine.drug

الوصف: Introduction The haemostatic and biochemical abnormalities participate in the progression of cardiovascular disease (CVD) in peritoneally dialysed (PD) patients. Recently, the role of kynurenine (KYN) pathway of tryptophan (TRP) degradation in the development of CVD has been postulated. Materials and methods The present study was undertaken to investigate haemostatic parameters, biochemical profiles and kynurenines in PD patients both with and without CVD compared to age- and sex-matched healthy controls. Results The multiple biochemical abnormalities were present in PD patients, particularly in those with CVD. Tissue factor (TF), its inhibitor (TFPI), prothrombin fragment 1+2 (F 1+2 ) , urokinase-type plasminogen activator (uPA), its soluble receptor (suPAR), plasmin/antiplasmin (PAP) complexes, KYN, kynurenic (KYNA) and quinolinic (QA) acids levels were significantly higher, whereas TRP was significantly lower in the PD patients than in the controls. Tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were higher in the patients with CVD than in the patients without CVD and controls. PD patients with CVD had higher F 1+2, and they had lower suPAR and KYNA levels compared with PD patients without CVD. KYNA was positively associated with TFPI, whereas its was inversely associated with F 1+2 both in the whole PD group and in CVD patients. Logistic regression analysis showed that low KYNA, high glucose, low HDL-cholesterol levels and the duration of dialysis treatment were independently associated with the presence of CVD in PD patients. Conclusions The present study suggests a relationship between kynurenine pathway of tryptophan degradation, haemostatic and biochemical disturbances and CVD prevalence in peritoneally dialyzed patients.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4c95c763c04bab7671b2430ba940fa01Test
https://pubmed.ncbi.nlm.nih.gov/19732942Test

المؤلفون: Alexandre Quintanilha, Susana Rocha, Irene Rebelo, Alice Santos-Silva, Luís Belo, Belmiro Patrício, Cristina Catarino, Elisabeth Castro

المصدر: Thrombosis research. 123(2)

مصطلحات موضوعية: Adult, medicine.medical_specialty, Mothers, Tissue plasminogen activator, Umbilical cord, Fibrin, Preeclampsia, Fibrin Fibrinogen Degradation Products, chemistry.chemical_compound, Pre-Eclampsia, Pregnancy, Internal medicine, Plasminogen Activator Inhibitor 1, medicine, Humans, Endothelial dysfunction, Hemostasis, biology, business.industry, Infant, Newborn, Hematology, medicine.disease, Fetal Blood, medicine.anatomical_structure, Endocrinology, chemistry, Plasminogen activator inhibitor-1, Cord blood, Case-Control Studies, Tissue Plasminogen Activator, Immunology, biology.protein, Female, business, Biomarkers, medicine.drug

الوصف: Endothelial cell activation or damage is believed to play a key role in preeclampsia (PE) and may underlie the hemostatic changes observed in this syndrome. The aim of this study was to evaluate a relationship between maternal and cord blood hemostatic disturbances in preeclamptic pregnancies. We measured the plasma levels of tissue plasminogen activator (tPA) antigen and of plasminogen activator inhibitor type 1 (PAI-1) antigen, both markers of hemostatic and endothelial function, and fibrin fragment D-dimer. Maternal blood from uncomplicated (n=42) and PEc pregnancies (n=44) were collected before delivery, and umbilical cord blood (UCB) immediately after delivery. In preeclamptic cases, UCB presented significantly higher tPA values and significantly lower PAI-1/tPA ratio. Preeclamptic women also presented significantly higher tPA, as well as PAI-1 values, when compared with normal pregnant women; no significant difference was found for D-dimer. In preeclamptic women, proteinuria (a marker of PE severity) correlated positively and significantly with tPA and PAI-1 antigen levels. An inverse relationship between maternal tPA antigen levels and fetal birth weigh in PE was also observed. Our data show that the hemostatic maternal disturbances observed in preeclamptic women have similarities with the UCB circulation, and that endothelial dysfunction is the most plausible underlying cause. Moreover, maternal hemostatic disturbances seem to be associated with the severity of PE. Further studies are needed to strength the values of tPA and PAI-1 as markers of severity in PE.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::69753aa9b2bf7067243f2e90c475bba5Test
https://pubmed.ncbi.nlm.nih.gov/18384840Test