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)

UFH and its derivatives, LMWHs, are effective and safe in the prevention and treatment of DVT. The mechanism for this effectiveness has been difficult to explain, given that the anti-IIa activity of LMWHs is important for their antithrombotic activity and the reported half-life of the anti-IIa activity of LMWHs is very short. The standard chromogenic anti-IIa assay is performed in an artificial system consisting of highly diluted plasma to which antithrombin III is added. It is possible, therefore, that the apparently short half-life of the anti-IIa activity is dependent on the limitations of the anti-IIa assay, commonly used in the pharmacokinetic studies. We have developed an anti-IIa assay that is more sensitive than the standard one. Our assay is based on the ability of UFH or LMWHs to catalyze the formation of TAT complexes. PTNA was able to detect in vitro the anti-IIa activity produced by 0.01 anti-Xa IU/mL of UFH or 0.05 anti-Xa IU/mL of LMWHs. Ex vivo, it was able to describe the time course of plasma anti-IIa activity of very low doses of UFH (intravenous or subcutaneous) or LMWHs. To characterize better the role of the anti-IIa activity of LMWHs, the pharmacokinetic properties of two of these agents have been evaluated in humans, assessing the anti-IIa activity by PTNA. Fraxiparine, 7500 and 10,000 ICU, and Enoxaparine, 20 and 40 mg, were administered subcutaneously to six healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma thrombin neutralization assay: pharmacokinetic applications. 782 61

The occurrence of a "rebound hypercoagulable state" in patients after dicontinuation of oral anticoagulants is still a matter of debate and no definite recommendation can be made on the best procedure for anticoagulant withdrawal. The present study investigated the changes in the levels of markers of activated blood coagulation in 32 patients (pts) in whom warfarin treatment (for venous thromboembolic disease) was randomly withdrawn abruptly (n = 17, group A) or gradually (n = 15, group B: 2/3 of initial dose the 1st week, 1/3 the 2nd weeks and nothing from the 3rd week on). Blood was sampled at baseline, once a week for the first three weeks and after 2 months. At the 1st week group A had significantly higher F1+2 and TAT values (p < 0.001); at the 2nd week F1+2 levels remained higher (p < 0.05) though INR values were not different from those of group B. After baseline, higher than normal F1+2 levels were recorded in 32/66 (48%) controls in group A vs 15/60 (25%) in group B (p < 0.01); at the 2nd week, 10/17 (59%) patients in group A vs 1/15 (7%) in group B still had higher than normal F1+2 levels (p < 0.01). The values of areas under curve (AUC) and maximum concentrations of all variables were not statistically different in the two groups; however, very high levels were observed in a few cases of group A. Thrombotic events (one DVT recurrence and one thrombophlebitis in a varicose vein) occurred in 2 pts of group A, both with high F1+2 and TAT AUC values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of blood coagulation after abrupt or stepwise withdrawal of oral anticoagulants--a prospective study. 783 56

This study investigated whether the pre-surgical plasma levels of TAT and F1 + 2 of patients undergoing major surgery for localized tumours could identify patients at higher risk of thrombosis, and how heparin prophylaxis affected in vivo coagulation after cancer surgery. We measured the pre- and post-operative levels of TAT, F1 + 2, total factor VII (FVIIt) and zymogen FVII (FVIIz) in 117 cancer patients, with and without heparin prophylaxis. The end points of this study were DVT, initially detected by 125I-fibrinogen uptake test and confirmed by ascending venography. Pre-operative [TAT] and [F1 + 2] of the cancer patients were significantly higher than those of age-matched control subjects (n = 50) (P < 0.005 and P < 0.05, respectively); pre-operative [FVII] was not significantly different. One of the 83 patients receiving prophylaxis, and 8/34 not receiving prophylaxis developed post-operative DVT. Of the parameters evaluated, only the pre-operative [TAT] > 3.5 ng/ml identified patients at higher risk for post-operative DVT. Heparin reduced plasma TAT levels and FVII consumption following surgery, suggesting that heparin modulates coagulation associated with cancer surgery. The results of this study also suggest that the pre-operative [TAT] may identify patients with higher risk for post-operative DVT.
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PMID:Preliminary study to identify cancer patients at high risk of venous thrombosis following major surgery. 791 39

Seventy-eight patients having elective total hip replacement were randomised into 3 groups A) control; B) low molecular weight heparin: (enoxaparin 40 mg once daily) and C) enoxaparin (40 mg once daily) plus graduated elastic compression (TEDR stockings) for 8-12 days. All patients had a preoperative perfusion lung scan and chest X-Ray and a postoperative perfusion/ventilation scan together with bilateral ascending venography on days 8-12. A blood sample was taken preoperatively, on the 1st, 3rd and 5th postoperative day and at the end of the study. The control group received placebo injections. The venograms and V/Q scans were reported blindly by an independent panel of three and one radiologists respectively. An independent panel of assessors stopped entry in the control group when a total of 45 patients were admitted according to Ethics Committee directives. The study continued with groups B and C. The incidence of DVT (including isolated asymptomatic calf thrombi) was as follows: Group A (n = 14) 93%; Group B (n = 32) 38%; Group C (n = 32) 25% (chi 2; p < 0.001 for group A versus B or C). The incidence of proximal DVT was: Group A 57%; group B 28%; group C 13% (chi 2; p = 0.057 for group A versus B and p < 0.005 for group A versus C). The incidence of silent pulmonary embolism (PE) (new defect on V/Q scan) was 28% (8 out of 29) in patients with and 5% (2 out of 43) in patients without DVT (chi 2; p < 0.02). The combination of high TAT and low anti-Xa activity on the 1st postoperative day identified a high risk group of patients who had a 56% incidence of proximal DVT on the 8th to 12th postoperative day. Further studies are needed to confirm the suggested increased efficacy in prophylaxis by the combination of LMWH and GEC as compared with LMWH alone.
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PMID:Deep venous thrombosis prophylaxis with low molecular weight heparin and elastic compression in patients having total hip replacement. A randomised controlled trial. 880 42

A new test for the determination of fibrin monomer in plasma was clinically evaluated in comparison to the plasma concentration of D-D, TAT and F1,2 for the early diagnosis of prethrombotic conditions. For this purpose 129 patients who underwent abdominal surgery were followed longitudinally. 12 patients developed DVT postoperatively, proved by phlebography. The identical specificity level 73.2% was chosen for all 4 tests. At this specificity, FM had the highest sensitivity (91.7%), followed by D-D (75.0%), TAT (41.7%) and F1,2 (33.3%). All FM-positive DVT-patients had pathological FM-values at least one day prior to the clinical manifestation of thrombosis. In a group of 255 obviously healthy persons the cut-off value for the new FM test was determined at 3.6 mg/l (95th percentile). No clinically relevant influence of gender, age, smoking habits or oral anticonception could be observed. It is concluded that FM is a valuable diagnostic tool for the early diagnosis of prethrombotic conditions.
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PMID:The value of quantitative fibrin monomer determination in the early diagnosis of postoperative deep vein thrombosis. 882 39

Eight patients with femoro-popliteal or sural DVT, confirmed by phlebography, were treated with intravenous Desmin (LMW-dermatan sulphate): on the first day, after an initial i.v. injection of 400 mg, all patients received an infusion of 800 mg in 500 ml of saline, during 24 hours; this infusion was repeated in each of the subsequent 9 days (global treatment period: 10 days). To monitor efficacy of the antithrombotic treatment a phlebography, with calculation of Marder score, was repeated at the end of treatment. Laboratory tests monitoring blood coagulation were carried out: aPTT, TT, PT. Factor Xa inhibition (by chronometric and chromogenic method), Stachrom DS, fibrinogen, prothrombin fragments F1 + 2 and TAT. Seven patients completed the ten-day treatment: 6 patients evidenced good improvement of the phlebographic patterns, 1 remained stationary and 1 patient was withdrawn due to adverse events. During the ten days treatment we did not observe any variation of blood coagulation tests. Desmin tolerability was good and no haemorrhagic episodes were registered. The collected results point to a good antithrombotic activity of the new LMW-dermatan sulphate, that deserves to be further evaluated with controlled investigations on larger number of patients.
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PMID:The treatment of deep vein thrombosis with continuous intravenous low-molecular-weight dermatan sulphate (Desmin). A pilot study. 898 60