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

In seven patients who had to be dialysed between four and 13 times due to acute renal failure, low molecular weight heparin (LMWH) Fragmin was used for anticoagulation. According to dose-finding studies, 80-90 U kg-1 body weight of LMWH as a single bolus were administered initially, producing dose-related levels of 0.3-1.5 anti-factor Xa U ml-1 in plasma. Apart from the anti-Xa activity in the plasma, the thrombin anti-thrombin III complex (TAT complex) and a fibrin degradation product (D-dimer) were measured as parameters of a coagulation activation. A sufficient anti-coagulation during dialysis was supposed to exist at a normal range (5.0 micrograms l-1 or below) of TAT complex. Pathological TAT concentrations at the end of dialysis indicated the requirement of an increased dose for the next dialysis. These concentrations reflected a need for more heparin if, for example, inflammation, indicated by increasing C-reactive protein levels (CRP), occurred. The increase of TAT complex and D-dimer during dialysis showed a good agreement (p less than 0.001). Due to a single bolus application before dialysis, one measurement of TAT at the end of the dialysis was sufficient. The determination of the TAT complex concentration enabled a heparinization better adapted to the clinical situation of intensive-care patients undergoing acute dialyses, so that the coagulation system was not additionally activated by the extracorporeal circulation.
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PMID:The control of anti-coagulation in acute dialyses with sensitive laboratory parameters. 133 80

The interaction of vitronectin-thrombin-antithrombin III (VN.TAT) complex with endothelial cells (EC) was investigated. Binding was specific and time- and concentration-dependent. Kinetics revealed an apparent dissociation constant of 16 nM and 1.7 x 10(5) binding sites/endothelial cell. The binding determinant of the ternary complex was located on the VN moiety. Since the association of VN to TAT adds its specific properties to the VN.TAT complex, the involvement of the heparin binding domain and the cell attachment site of VN was investigated. Neither addition of RGD peptide nor blocking of the vitronectin receptor with a monoclonal antibody interfered with VN.TAT binding to EC. Addition of heparin, a VN-derived peptide comprising two heparin binding consensus sequences or a monoclonal antibody directed against the heparin binding domain on VN, completely inhibited VN.TAT binding to EC. These results indicate that the interaction is mediated through the heparin binding domain of VN. Digestion of heparan sulfate proteoglycans resulted in a decrease of VN.TAT binding to EC, indicating the involvement of heparin-like structures on the EC surface. Our findings point to an unrecognized mechanism by which VN may act as scavenger in order to enhance the clearance of end products of the clotting system via binding of the ternary VN.TAT complex to the luminal surface of EC.
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PMID:Binding of vitronectin-thrombin-antithrombin III complex to human endothelial cells is mediated by the heparin binding site of vitronectin. 137 Aug 15

In a crossover study conducted with eight uremic patients maintained on hemodialysis, the Authors compared the effects of heparin (100 IU/kg at the start of dialysis) and defibrotide (400 mg at the start, repeated at 2 hours of ongoing dialysis) on the parameters of blood coagulation (VIII:C, AT III, TAT, PC antigen and activity, PS, and FPA), each being assessed before dialysis and at 2, 3 and 4 hours of the ongoing procedure. Heparin-assisted dialysis resulted in a significant rise of VIII:C and AT III; with defibrotide, instead, there was evidence of thrombin activation (increased FPA and TAT). PC levels were raised with both dialysis modalities; however, PC activity and PS levels were increased only in defibrotide-assisted dialysis. There were no adverse reactions or evidence of fibrin formation. These results confirm the antithrombotic activity of defibrotide in the course of dialysis and indicate that this action is independent of thrombin neutralization.
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PMID:Hemodialysis with defibrotide: effects on coagulation parameters. 142 6

In order to elucidate the activation of the coagulation cascade in patients with malignant neoplasms, we measured the levels of plasma prothrombin fragment F1 + 2, which is liberated in the process of thrombin generation. Twenty healthy adults (Group A), 29 patients with malignancies not complicated with DIC (Group B) and 4 patients with DIC (Group C) were evaluated. The values of F1 + 2 in Group C (2.38 +/- 0.55 nmol/l) were significantly higher (p < 0.01) than those in Group A (0.52 +/- 0.19 nmol/l) and B (0.86 +/- 0.68 nmol/l). Many patients in Group B showed higher levels of F1 + 2 compared to normal subjects, however, no significant differences were found between Group A and B. With respect to other coagulation molecular markers such as TAT, D-Dimer and PIC, F1 + 2 levels revealed positive correlation to those levels. Concerning the clinical course of DIC, elevated levels of F1 + 2 normalized much rapidly than those of TAT and D-Dimer by continuous administration of heparin. In conclusion, the measurement of plasma F1 + 2 is important in monitoring the activation of coagulation system in patients with malignancies, especially with respect to early detection and treatment of DIC.
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PMID:[Evaluation of hypercoagulable state in patients with malignancies by using prothrombin fragment F1 + 2]. 146 81

Functional antithrombin III levels were measured by factor Xa inhibition in 63 members of a large family with type 2 antithrombin III deficiency and individuals were classified as antithrombin III deficient or non-deficient according to the results. F1 + 2 and TAT complexes were measured using an ELISA and FPA levels were measured by radioimmunoassay. Thirty subjects (48%) were classified as antithrombin III deficient and 33 (52%) as antithrombin III non-deficient. The mean level of F1 + 2 was significantly higher in the deficient adults (0.87 +/- 0.26) compared to both the non-deficient adults (0.70 +/- 0.21) (p = 0.03) and the deficient adults receiving warfarin (0.16 +/- 0.01) (p less than 0.001). The differences in the mean values of TAT complexes and FPA between deficient and non-deficient individuals were not statistically significant. These findings suggest that untreated antithrombin III deficient subjects generate more thrombin than their non-deficient family members and that warfarin inhibits this thrombin formation. In this cross-sectional study, it is not possible to correlate the levels of the surrogate makers with future clinical outcome.
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PMID:Measurement of markers of activated coagulation in antithrombin III deficient subjects. 151 14

We present a 65-year-old female with myelodysplastic syndrome (MDS) who has attended our O.P.D. since 1983. In early December, 1990, dyspnea on effort developed which then progressed to dyspnea at rest at the end of December. She was admitted on January 8 with orthopnea. Chest X-ray films revealed loss of vascular shadows of the right lung. Blood gas analysis showed hypoxemia and hypocapnemia. Abnormalities in the coagulation-fibrinolytic system (increased TAT (thrombin-anti-thrombin III complex) and alpha 2-PIC (plasmin inhibitor complex)), possibly due to MDS, were detected. The diagnosis of pulmonary thromboembolism was made by pulmonary perfusion scintigram and pulmonary arteriography. After commencement of anticoagulation therapy on January 15, the subjective symptoms, blood gas analysis, pulmonary scintigram, and disorders of the coagulation-fibrinolytic system improved. The patient was discharged on March 5, 1991. The present case of myelodysplastic syndrome was associated with abnormalities of the coagulation-fibrinolytic system and was complicated by pulmonary thromboembolism.
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PMID:[Pulmonary thromboembolism associated with myelodysplastic syndrome]. 156 27

It has been suggested that unstable angina at rest, like acute myocardial infarction, might be associated with a thrombotic process. In order to study the hypothesis that myocardial ischemia during exercise could also be associated with an activation of blood coagulation and/or fibrinolysis, we investigated the presence of plasma markers of a prethrombotic or thrombotic state (thrombin-antithrombin III complexes TAT, prothrombin fragment F1 + 2, and D-dimers DD) in 100 consecutive patients with confirmed or suspected coronary artery disease during ergometric test with myocardial thallium-201 scintigraphy. Symptoms and scintigrams allowed to define three groups of patients: those showing no ischemia (n = 79) and those with symptomatic (n = 8) or silent myocardial ischemia (n = 13). Before exercise, DD and TAT levels were not significantly different among the three groups. On the other hand, the F1 + 2 levels were slightly albeit significantly higher in the patients without ischemia than in the patients with symptomatic or silent ischemia. After exercise, no significant difference was found between the three groups. Exercise induced a significant and parallel increase in both the TAT and the F1 + 2 levels (but not of the DD levels) in the three groups. Thus, our study does not support the hypothesis that myocardial ischemia, silent or symptomatic, is associated with an activation of plasma coagulation and fibrinolysis that can be distinguished from the exercise-induced thrombin generation.
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PMID:Effects of exercise test on plasma markers of an activation of coagulation and/or fibrinolysis in patients with symptomatic or silent myocardial ischemia. 160 40

Amidolytic chromogenic substrate assays are frequently used to determine the anticoagulant activities of various commercial heparins. With the help of a combined assay method heparin characterization is made possible using the TAT/XAT quotient under consideration of the simultaneous inhibition of the two serine proteases thrombin and factor Xa by antithrombin III. The test is primarily designed for qualitative characterization where a numerical value can be assigned to every heparin. However, quantitative aspects may also be evaluated.
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PMID:Evaluation of an amidolytic test for comparative calibration of HMW- and LMW-heparins. 166 65

In order to assess the thrombin and plasmin generation in vivo in disseminated intravascular coagulation (DIC), plasma levels of thrombin-antithrombin III (ATIII) complex (TAT) and plasmin-alpha 2-antiplasmin (a2AP) complex (PAP) were measured together with standard coagulation and fibrinolytic parameters in 80 patients with DIC. Both TAT and PAP were markedly elevated in patients with DIC. When plotted by the underlying disease categories, differences in the magnitude of the elevations of these complexes were recognized among groups. Patients with acute promyelocytic leukemia (APL) had the highest PAP, the lowest TAT/PAP ratio, low a2AP, and low fibrinogen, indicating that the most excessive fibrinolysis can occur in APL. Similar profiles, although less marked, were observed in patients with other leukemias and vascular diseases. Patients with sepsis showed the highest TAT/PAP ratio and the lowest PAP with no decrease in a2AP or fibrinogen, demonstrating a relatively impaired fibrinolysis. Patients with cancer had a relatively high TAT and high TAT/PAP ratio. In addition, both TAT and PAP were markedly elevated in patients with shock. From these, it was suggested that, although laboratory manifestations in DIC are extremely variable from patient to patient, underlying disorders are, at least in part, responsible for the observed variations. Recognition of this variable activation of coagulation and fibrinolysis would be helpful for the proper management of patients with DIC.
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PMID:Thrombin vs. plasmin generation in disseminated intravascular coagulation associated with various underlying disorders. 200 32

Routine postoperative monitoring of plasma coagulation and fibrinolysis system values after cesarean delivery in 191 women who did not develop thrombosis and 16 who did revealed a preoperative defect in the fibrinolysis (PAI, TAT) and inhibitor (AT III) systems. Significant postoperative correlations in the drop in antithrombin levels could not be explained solely by hemodilution. Moreover, a disturbance of the equilibrium of the alpha-2 increase and plasminogen was observed, favouring alpha-2 antiplasmin. Hydroxyethyl starch is capable of simultaneously influencing hypercoagulability and postoperative status. The only difference noted between the two groups of drugs was in the course of the PAI concentration (P less than 0.02). It would therefore appear logical in clinical practice to extend preoperative tests to include determination of the plasminogen activator inhibitor and the thrombin-antithrombin complex.
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PMID:[Changes in plasma coagulation and fibrinolysis following cesarean section and relationship to deep venous thrombosis. Results of a randomized prospective comparative study with 6% hydroxyethyl starch 0.62 and low-dose heparin as thrombosis prophylaxis]. 171 8


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