Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epidemiologic studies have shown that exposure to particulate air pollution is associated with short-term increases in cardiovascular morbidity and mortality. These adverse effects of inhaled particulate matter (PM*) may be the indirect result of a PM-induced increase in blood coagulability. This explanation is biologically plausible because prospective studies have shown that increases in blood coagulation parameters are significantly associated with risk of adverse cardiovascular events. We examined the hypothesis that acute exposure to elevated levels of PM causes prothrombotic changes in blood coagulation parameters. Rats with indwelling jugular vein catheters were exposed for 6 hours to filtered air or concentrated ambient PM in New York City air (n = 9 per group per experiment). PM less than 2.5 microm in mass median aerodynamic diameter (PM2.5) was concentrated for animal exposures using a centrifugal concentrator. Blood samples were taken at four time points: before and immediately after exposure and at 12 and 24 hours after the start of exposure. At each time point, six coagulation parameters (platelet count, fibrinogen level, factor VII activity, thrombin-antithrombin complex [TAT] level, tissue plasminogen activator [tPA] activity, and plasminogen activator inhibitor [PAI] activity) were measured as well as all standard blood count parameters. Five concentrated-PM exposure experiments were performed over a period of 8 weeks in the summer of 1999. PM exposure concentrations ranged from 95 to 341 microg/m3. Statistical significance was determined by two-way analysis of variance (ANOVA) on the postexposure data with time and exposure status as main effects. There were no consistent exposure-related effects on any of the end points across the five experiments and no indication of any dose-dependent effects. Most of the statistically significant differences that were observed do not represent adverse effects. Therefore, the results of this study do not indicate that exposure to concentrated ambient PM causes adverse effects on blood coagulation in healthy rats.
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PMID:Effect of concentrated ambient particulate matter on blood coagulation parameters in rats. 1250 39

Kidney transplant recipients are not only prone to dyslipidemia but also have a high risk of cardiovascular death. Impairment of the fibrinolytic system is thought to be one factor playing a role in development of thrombotic complications. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a glycoprotein, linking coagulation and fibrinolysis. The purpose of this study was to assess TAFI concentrations and activities in renal transplant recipients stratified based upon serum cholesterol values above 220 mg/dL or below 200 mg/dL. The groups did not differ regarding age, creatinine clearance, BMI, time after transplantation, albumin, fibrinogen, thrombomodulin, or PAP. Additionally, we evaluated thrombin activity (thrombin-antithrombin complex TAT, prothrombin fragments 1 + 2); TAFI activator; thrombomodulin (TM), catalyzer of TAFI activation; and the degree of plasmin generation (plasmin-antiplasmin complex PAP) using commercially available kits. In patients with hyperlipidemia significantly higher TAFI concentrations and activities may contribute to prolonged ECLT and lowered fibrinolytic activity index (FAI). Increased levels of F1 + 2 and TAT were observed in hypercholesterolemic patients, indicating enhanced thrombin generation. Elevated TAFI concentration, and activities and enhanced thrombin generation observed in hypercholesterolemic kidney transplant recipients may contribute to hypofibrinolysis and progression of atherosclerosis in this group of patients.
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PMID:Thrombin-activatable fibrinolysis inhibitor in kidney transplant recipient with dyslipidemia. 1452 94

Deep vein thrombosis (DVT) is reported in up to 40% of trauma patients. The individual risk is nearly unpredictable. A daily single dose of a low molecular weight heparin (LMWH) was administered as prophylaxis to 518 trauma patients who were examined preoperatively and up to 10 days postoperatively in a prospective study. They were divided into two groups: group I comprised surgery of the hip and femur as well as total knee replacement and group II knee and lower leg surgery. Thrombin-antithrombin complex and D-dimer were analyzed. A second daily dose of LMWH was added if D-dimer exceeded the cutoff. If ultrasound was suspicious for DVT venography was added. Deep vein thrombosis was seen in five cases (group I=4, group II=1), without pulmonary embolism. TAT and D-dimer were significantly higher in group I than in group II ( p<0.005). One hundred patients, 79 of them belonging to group I, were treated with a second dose of LMWH. The daily cutoff had the highest sensitivity and specificity for day 4. Due to individual monitoring of coagulation markers, the risk for thromboembolism compared to actual data in the literature seems to be reduced.
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PMID:[Prevention of thromboembolism in trauma surgery by dose adjustment of low molecular weight heparin depending on levels of TAT and D-dimer]. 1472 38

A lacunar infarct is defined as the occlusion of a single perforating artery. Certain researchers have proposed that patients with lacunar infarcts can be classified into two clinically distinct entities: patients with a single, symptomatic lacunar infarct, and patients with multiple lacunar infarcts together with hypertension and leukoaraiosis. The present study attempted to delineate the characteristics of lacunar infarcts and evaluate the validity of the aforementioned hypothesis. A total of 130 consecutive patients with first-time symptomatic lacunar infarct were studied. All patients were dichotomized into two groups according to two different kinds of models as follows. Model-1: patients with a single lacune and patients with multiple lacunes; and Model-2: patients with large lacune and patients with small lacune. Associated factors for the multiple lacune group compared with the single lacune group as well as the large lacune group compared with the small lacune group, were analyzed by multivariate logistic regression analysis. Associated factors included age, sex, hypertension, diabetes mellitus, dyslipidemia, smoking, extracranial and intra-cranial vascular lesions, extent of lacunes and white matter lesions, progression status and blood pressure in the acute stage, and coagulation markers such as fibrinogen, thrombin-antithrombin complex, D-dimer, beta-thromboglobulin, platelet factor 4. Results for Model-1: hypertension (age-and sex-adjusted OR: 2.58, p = 0.017) and elevated systolic blood pressure (>160mmHg for the mean value during the first post-ictal week; OR: 2.55, p = 0.016) were significantly associated with the multiple lacune group. Large lacunes (>10mm in diameter) were negatively associated with the multiple lacune group (OR: 0.38, p = 0.017). Association between confluent white matter lesions and the multiple lacune group approached significance (OR: 2.16, p = 0.056). Results for Model-2: female sex (OR: 0.39, p = 0.021), mild stenosis of intracranial and extracranial arteries (<25%) (intracranial; OR: 5.42, p = 0.0042, extracranial; OR: 3.30, p = 0.016), progressing stroke (OR: 6.77, p<0.0001), and high levels of TAT (>3ng/ml) (OR: 2.80, p = 0.039) were significantly associated with the large lacune group. Multiple lacunes (OR: 0.38, p = 0.016) and confluent white matter lesions (OR: 0.28, p = 0.007) exhibited a significant negative association with the large lacune group. In conclusion, underlying vasculopathy in the presence of multiple lacunes may correspond to lipohyalinosis resulting from hypertension. Moreover, large lacune may correspond to microatheroma at the orifice of penetrating arteries.
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PMID:[Clinical classification for lacunar infarct. An investigation of 130 consecutive cases of lacunar infarctions]. 1571 93

Eccentric exercise can cause skeletal muscle damage with ultrastructural disruption, inflammation and increased proteolytic enzyme activity. It may be possible that these changes are able to trigger blood coagulation in vivo. The aim of the study was to investigate changes in blood coagulation via the measurement of aPTT, the thrombin potential (total [TTP] and endogenous [ETP], both intrinsic [in] and extrinsic [ex]) and the thrombin generation (prothrombinfragment 1 + 2 [F1 + 2] and thrombin-antithrombin complex [TAT]) after pure eccentric exercise. Seventeen healthy non-smokers (28 +/- 6 years, VO2-peak 59 +/- 7 ml/min/kg) underwent pure eccentric down jumps (9 x 28 isolated down jumps in 90 min, drop from a height of 55 cm), a cycle exercise (90% of the individual anaerobic threshold for 60-90 min) and a control experiment on different days. Blood samples were drawn after a 30-min rest, immediately, and 2 h after exercise. After the cycle exercise, a clear shortening by 12% (P<0.001) in aPTT and an increase in TTPin (13%; P<0.05) and TAT (33%; P<0.05) in comparison to the control experiment were seen, while after eccentric exercise only minimal changes in aPTT and thrombin potential (TTPin, ETPin) and no thrombin generation (F1 + 2 and TAT) were found. In contrast to concentric dynamic exercise, e.g. cycle ergometry, only insignificant changes in thrombin potential and no thrombin generation could be observed after skeletal muscle damage induced by pure eccentric exercise. It can be concluded that the mechanical impact associated with eccentric exercise does not activate blood coagulation.
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PMID:Pure eccentric exercise does not activate blood coagulation. 1590 78

Therapeutic options for developing countries have to assure an optimum safety and efficacy and low-cost antihaemophilic concentrates. A single blind randomized crossover study was carried out in 12 previously treated HB patients, comparing the pharmacokinetics (PK), thrombogenicity (TG) and safety of two plasma-derived double-inactivated (solvent/detergent heating at 100 degrees C, 30 min) factor IX (FIX) concentrates, UMAN COMPLEX DI (product A) [plasma-derived prothrombin concentrates (PCC)] and a high purity FIX concentrate AIMAFIX DI (product B, HPFIX). In a non-bleeding state, they received one single intravenous dose 50 IU FIX kg(-1) of PCC or HPFIX, and after a wash-out period of 14 days, the other product. We evaluated acute tolerance and determined PK parameters based on FIX levels measured over a 50 h postinfusion period. We studied fibrinogen, platelets, antithrombin, F1 + 2, TAT, D-dimer, over a 360 min postinfusion period. Ten cases remained in on-demand treatment for 6 months, five with PCC and five with HPFIX. PK and anti-FIX inhibitors were repeated at 3 and 6 months. No inhibitors were detected. PK values (PCC vs. HPFIX): clearence (CL; mL h(-1) kg(-1)) 5.2 +/- 1.4 vs. 6.5 +/- 1.4; the volume of distribution at steady state (mL kg(-1)) 154.9 +/- 54.9 vs. 197.5 +/- 72.5; mean residence time (h) 29.7 +/- 8.1 vs. 30.7 +/- 9.2; T(1/2) (h) 22.3 +/- 7 vs. 23.5 +/- 12.3; incremental recovery (IR; U dL(-1) U(-1) kg(-1)) 0.96 +/- 0.17 vs. 0.76 +/- 0.13. HPFIX showed significant lower IR and higher CL. There were no differences in PK at 3 and 6 months. In TG, significant increments in TAT and F1 + 2 at 30 min and 6 h were found with PCC. Product B PK results agrees with reported results for other HPFIX preparations. Use of PCC product A has to consider its thrombogenic activity.
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PMID:Pharmacokinetics, thrombogenicity and safety of a double viral inactivated factor IX concentrate compared with a prothrombin complex concentrate. 1623 7

Kidney transplant recipients are prone to hypertension, dyslipidemia, and cardiovascular death. Hypertension is associated with hemostatic abnormalities. Thrombin activatable fibrinolysis inhibitor (TAFI) is a glycoprotein that links coagulation and fibrinolysis. The purpose of this study was to assess TAFI concentrations in renal transplant recipients in relation to blood pressure. Additionally, we evaluated thrombin activity (thrombin-antithrombin complex [TAT], prothrombin fragments 1+2 [F1+2]), thrombomodulin (TM), and the degree of plasmin generation (plasmin-antiplasmin complex [PAP]) using commercially available kits. The studies were performed on 86 renal allograft recipients (48 women, 38 men) at age range 26 to 73 years. The immunosuppressive regimen consisted of cyclosporine (CsA), prednisone, and azathioprine (n = 58) or mycophenolate mofetil (MMF; n = 28). All patients maintained sufficient and stable graft function, showing no clinical signs of rejection. In patients with hypertension (n = 68), we observed significantly higher concentrations of TAFI and of markers of thrombin generation (F1+2, TAT), and of thrombomodulin with significantly prolonged euglobulin clot lysis time (ECLT), which reflects overall fibrinolytic activity and lower fibrinolytic activity index (FAI). Both groups did not differ with respect to age, creatinine clearance, body mass index, time after transplantation, albumin, fibrinogen, and PAP. Diastolic blood pressure correlated significantly with TAFI concentrations, uric acid, and prednisone dose, whereas systolic blood pressure correlated with urea, uric acid, creatinine clearance, and MCV. Elevated TAFI concentrations and enhanced thrombin generation in hypertensive kidney transplant recipients may contribute to the hypofibrinolysis and progressive atherosclerosis in this population. Blood pressure was related to kidney function, maintenance prednisone dose, and TAFI concentration.
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PMID:Thrombin activatable fibrinolysis inhibitor in hypertensive kidney transplant recipients. 1650 76

Increased thrombogenicity of drug-eluting stents (DESs) has recently been reported. The aim of the present study was to investigate the prothrombogenic effect of DESs and Bare stents, and determine factors predictive of acute stent thrombosis (AST) in preclinical experiments using new stent design or coating. Circulating pre- and post-stenting parameters of platelet activation (mean platelet volume, MPV; platelet distribution width, platelet large cell ratio), thrombin activation (thrombin-antithrombin complex, TAT and prothrombin fragments, F1+2), tissue factor antigen (TF-ag) and -activity (TF-act) and plasminogen activator inhibitor-1 (PAI-1) were measured in 141 consecutive pigs. Stent implantations were performed after pretreatment with aspirin and clopidogrel with unfractionated heparin anticoagulation. Nineteen pigs (groups AST-DES, n = 12; and AST-Bare, n = 7) died mean 6.3 +/- 2.9 h after stent implantation from AST. The remaining 122 control (C) pigs (groups C-DES, n = 76, and C-Bare, n = 46) survived the 1-month follow-up. Non-significantly elevated levels of post-stent F1+2 and TAT were measured in AST groups. Post-stenting MPV was increased significantly in the groups ASTDES and AST-Bare as compared with the groups C-DES and C-Bare (11.73 +/- 1.12 and 11.6 +/- 0.68 vs. 8.85 +/- 0.78 and 9.04 +/- 0.81 fL; p < 0.001), similarly to TF-ag (189.1 +/- 87.5 and 127 +/- 34.9 vs. 42.5 +/- 24.6 and 35.3 +/- 37.6 pg/ml; p < 0.001, respectively), Tfact (3.23 +/- 0.95 and 2.73 +/- 1.68 vs. 1.43 +/- 1.12 and 1.61 +/- 1.31 pM; p < 0.01, respectively) and PAI-1 (99.1 +/- 15.8 and 99 +/- 14.7 vs.53.4 +/- 40.2 and 46.9 +/- 42.4 ng/ml;p < 0.01, respectively). Multivariate analysis revealed elevated post-stenting plasma levels of TF-ag (p = 0.016) and MPV (p = 0.001) as independent risk factors for developing AST within the first 24 h in a porcine coronary stent model.
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PMID:Platelet activation and high tissue factor level predict acute stent thrombosis in pig coronary arteries: prothrombogenic response of drug-eluting or bare stent implantation within the first 24 hours. 1689 65

Coagulation abnormalities have been implicated in the pathogenesis of sepsis and organ dysfunction. Nitric oxide (NO) is regarded as a critical mediator of many vascular pathologies, including sepsis. However, limited evidence is available to document a relationship between NO generated by inducible NO synthase (iNOS) and hemostatic abnormalities in sepsis. Therefore, we evaluated the effects of selective iNOS inhibition on markers of endothelial and coagulation homeostasis in a clinically relevant model of porcine bacteremia induced and maintained for 24 hours (h) with a continuous infusion of live P. aeruginosa. After 12 h of sepsis, animals received either vehicle (Control, n=7) or continuous infusion of selective iNOS inhibitor L-NIL (n=7). Before as well as 12, 18 and 24 h after starting P. aeruginosa following variables related to i) endothelial dysfunction (von Willebrand factor [vWf]; tissue plasminogen activator activity [t-PA]; ii) coagulation (thrombin-antithrombin complexes [TAT]; platelet count); iii) fibrinolysis (t-PA activity, activity of plasminogen activator inhibitor type 1 (PAI-1 act); and iv) oxidative/nitrosative stress (isoprostanes, nitrate/nitrite levels) were measured. L-NIL inhibited sepsis-induced increase in plasma nitrate/nitrite and isoprostanes concentrations, prevented hypotension and acidosis. L-NIL significantly attenuated sepsis-induced rise in plasma vWF and TAT. P. aeruginosa-induced drop in t-PA activity was blunted by iNOS inhibition, while increased PAI-1 and reduced platelet count were not reversed by the treatment. In conclusion, selective iNOS inhibition was associated with attenuation of sepsis-induced coagulation and endothelial dysfunction suggesting the interplay between mediators of vascular system and hemostatic balance. Reduction of oxidative stress probably contributes to the beneficial effects afforded by iNOS blockade.
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PMID:Coagulation and endothelial dysfunction during longterm hyperdynamic porcine bacteremia--effects of selective inducible nitric oxide synthase inhibition. 1726 61

The transfusion of fresh-frozen plasma (FFP) is suggested to minimize dilution coagulopathy when applied instead of colloids during paediatric craniofacial surgery (pCFS). We prospectively compared plasmatic haemostaseologic function between volume replacement with FFPs versus human albumin (HA) in a pilot study. Thirty infants with primary craniosynostosis were scheduled for pCFS. In 15 of those, FFPs were available from the identical donor as for packed red blood cells (pRBC), and were thus employed for intraoperative volume replacement. The remaining 15 infants were infused with HA-5% instead. Haemoglobin(Hb)-values, global coagulation parameters (activated partial thromboplastin time-aPTT; prothrombin time-PT), selected clotting factors (F) (VIII, XI, XIII), antithrombin-AT, fibrinolytic factors (fibrinogen; plasminogen; alpha2-antiplasmin-alpha2A), and activation parameters (thrombin-antithrombin-complex-TAT; plasmin-antiplasmin-complex-PAP; D-dimers) were assessed and compared between both groups after induction of anaesthesia, before transfusion of pRBC, and at the end of surgery. Patients and treatment characteristics were balanced between both groups. Prolongation of aPTT and decreases of PT, FXI, FXIII, AT3, and fibrinolytic factors were more pronounced in the HA-group. Increases in F VIII activity, activation parameters, and the course of Hb-values were similar among both groups. There was no difference regarding clinical endpoints (peri-/postoperative pRBC-transfusions, postoperative blood loss). In conclusion, the application of HA was associated with a more distinct dilution of procoagulant factors, AT3, and fibrinolytic factors than the use of FFPs. However, the course of activation markers suggested a similar extent of clotting and fibrinolytic activation with the use of both transfusion regimens, and there were no differences with regard to clinical endpoints.
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PMID:Intraoperative fresh-frozen plasma versus human albumin in craniofacial surgery--a pilot study comparing coagulation profiles in infants younger than 12 months. 1759 10


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