Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibrinopeptide A (FpA), fibrin monomers, fibrinogen, fibrin degradation products (FDP) aand platelets have been studied during pregnancy, parturition and during toxemia and compared with normal non-pregnant controls in order to evaluate thrombin activity under these conditions. We found a significant rise in fibrinopeptide A levels in late pregnancy and even more so during parturition with a maximum immediately after placental expulsion. We also found elevated FpA levels in toxemic patients, but no significant differences from normal pregnancies. Fibrin monomers were more often elevated during delivery and toxemia during normal pregnancy. One case report concerning a patient with deficient thrombin activation and heavy postpartum bleeding is added. Our studies indicate an increased thrombin activity and fibrinogen turnover in both normal and toxemic pregnancies. During normal childbirth, coagulation activity seemed to reach a maximum immediately after placental separation.
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PMID:Fibrinopeptide A and intravascular coagulation in normotensive and hypertensive pregnancy and parturition. 651 13

Both clinical and laboratory findings suggest that pregnancy constitutes a hypercoagulable condition; yet none of the observed laboratory changes are specific for thrombosis. An essential step involves thrombin-mediated fibrin generation. In the process, fibrinopeptide A (FPA) is cleaved from fibrinogen. Using a radioimmune assay, FPA was determined prospectively in a longitudinal and cross-sectional fashion. Fibrinopeptide A increased significantly over control by the end of the first trimester, from 1.3 ng/ml to 2.8 ng/ml. It continued to increase until 30 to 32 weeks' gestation and then plateaued at 4.3 to 4.7 ng/ml. In the immediate postpartum period, FPA remains elevated. In conclusion, thrombin generation as reflected in FPA production is increased throughout pregnancy, thus confirming a hypercoagulable milieu.
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PMID:Fibrin generation in normal pregnancy. 673 46

Fibrinopeptide A (FPA), which is considered to be a quantitative indicator for the thrombin activity in vivo, was measured in 136 patients treated with phenprocoumon in order to obtain information on the effectiveness of the inhibition of the coagulation system. The results show a decrease of the FPA concentration in relation to the efficacy of the anticoagulant therapy as measured by the thrombotest coagulation method (p less than 0.01). However, elevated FPA was observed even under an effective oral anticoagulation. These data indicate that an increased thrombin activity cannot be completely prevented by oral anticoagulants in every patient. Combined measurement of FPA and the thrombotest coagulation methods might be used to detect patients with an elevated risk of recurrent thromboembolism despite treatment with phenprocoumon.
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PMID:Measurement of fibrinopeptide A in patients treated with phenprocoumon. 728 Nov 7

Clot-bound thrombin remains active and is less accessible to heparin-antithrombin III than fluid-phase thrombin. To determine whether clot-bound human thrombin is more susceptible to inactivation by direct thrombin inhibitors, the activity of a novel synthetic competitive thrombin inhibitor Ro 46-6240, recombinant hirudin and unfractionated heparin were compared with fluid-phase thrombin and clot-bound thrombin. Fibrinopeptide A generated in human plasma was used as an index of thrombin activity. Hirudin was the most potent inhibitor of fluid-phase and clot-bound thrombin. However, Ro 46-6240 inhibited clot-bound thrombin three times more potently than fluid-phase thrombin (IC50 19 vs 56 ng/ml) while hirudin was two times (IC50 8 vs 3 ng/ml) and heparin six times (IC50 1,205 vs 200 ng/ml) less active against clot-bound thrombin compared with fluid-phase thrombin. The relative selectivity for clot-bound thrombin is not a unique property of Ro 46-6240 since two other synthetic thrombin inhibitors tested inhibited clot-bound thrombin more effectively than fluid-phase thrombin and a third was equally active against both forms of thrombin. In contrast, the affinities of two chromogenic substrates were similar for both forms of thrombin. This study shows that direct thrombin inhibitors inhibit clot-bound thrombin more potently than heparin and suggests that an apparent selectivity for clot-bound thrombin can be achieved with some synthetic thrombin inhibitors. Further studies have to show whether the high potency of these direct thrombin inhibitor translates into antithrombotic efficacy in clinical situations with pre-existing clots.
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PMID:Inhibition of clot-bound and free (fluid-phase thrombin) by a novel synthetic thrombin inhibitor (Ro 46-6240), recombinant hirudin and heparin in human plasma. 789 25

The effects of acute smoking on hemostatic functions were investigated in healthy young volunteers. Immediately after the volunteers smoked, a significant increase in blood pressure and heart rate was accompanied by a rise in plasma epinephrine. Fibrinopeptide A and thrombin-antithrombin III complex as markers of thrombin generation in vivo were significantly increased after smoking. The increase in thrombin-antithrombin III complex was significantly correlated with that of plasma epinephrine. Both antigen and activity of tissue plasminogen activator and plasmin-inhibitor complex as markers of fibrinolytic activity in vivo were markedly increased after smoking, whereas D-dimer, plasminogen activator inhibitor antigen, fibrinogen, and both beta-thromboglobulin and platelet factor 4 as markers of platelet activation in vivo were not changed. No effects were observed after sham smoking under exactly identical conditions in the same subjects. Thus thrombin generation was observed as acute hemostatic effects of smoking. Enhanced fibrinolytic response may counteract an increased procoagulant activity. Patients with vascular disease might be more susceptible to a state of disequilibrium in favor of coagulation, which may partly explain a mechanism by which cigarette smoking leads to cardiovascular morbidity and mortality.
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PMID:Thrombin generation as an acute effect of cigarette smoking. 801 87

BACKGROUND. Hypofibrinogenemia and increased fibrin(ogen) degradation products in acute leukemia have been attributed to intravascular thrombin generation triggered by leukemic cells. However, the strict relationship between fibrinogen catabolism and turnover of fibrinopeptide A (FPA), which is a sensitive and specific marker of thrombin activity, has not been evaluated in acute leukemia (AL) with or without disseminated intravascular coagulation (DIC) to see whether mechanisms other than thrombin activity could be responsible for fibrinogen consumption. We report here the 125I-fibrinogen kinetics and FPA measurements in 19 patients with AL, 6 of them with DIC. METHODS AND RESULTS. Radiolabelled fibrinogen kinetics were studied in all the patients concomitantly with the start of chemotherapy. Fibrinopeptide A was measured by a radioimmunoassay at time of diagnosis and during chemotherapy. The kinetics of disappearance of radiolabelled fibrinogen where biphasic, with a rapid phase in the first 1-3 days of chemotherapy and a subsequent slow phase associated with the reduction or disappearance of blast cells. Patients with DIC had a significantly shorter half-life and turnover than patients without DIC. The latter group had significant shortening of these parameters in comparison to normal subjects. The thrombin-dependent catabolic rate of fibrinogen, calculated from the mean level of FPA during the first phase of disappearance curve and by assuming 2 moles of FPA generated per mole of fibrinogen, was similar in patients without DIC and in normal subjects, whereas patients with DIC had a significantly higher catabolic rate, even though the increase was not sufficient to account for all the turnover of fibrinogen. No relationship was observed between fibrinogen turnover and FPA turnover.
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PMID:Fibrinogen survival and fibrinopeptide A in acute leukemia. 803 60

Fibrin deposition within the pleural space may influence repair following pleural injury. Although the mesothelial surface can organize fibrin, the contribution of pleural mesothelial cells to pleural repair is unknown. During coagulation thrombin cleaves Fibrinopeptide A (FPA, A alpha 1-16) and fibrinopeptide B (FPB) from the A alpha and B beta chains of fibrinogen to generate fibrin monomer. Since these peptides are mitogenic for human fibroblasts, we considered that they might stimulate replication of human pleural mesothelial cells (HPMC). Application of fluid expressed from fibrin clots significantly increased cell number and stimulated uptake of 3H-thymidine by HPMC compared with untreated cells. The mitogenic response of subconfluent HPMC to dilutions of clot fluid (30-150 micrograms/ml protein) was comparable to that of 0.1 nM TGF-beta. Fibrinopeptide A (7.5-30 microM) stimulated 3H-thymidine uptake in HPMC, but FPB had only a slight effect at 30 microM. Antibody to FPA antibody significantly attenuated the mitogenic effect of clot fluid, indicating that a major component is FPA. Our study suggests that fibrinopeptides released during fibrin formation in vivo may stimulate local mesothelial regeneration following pleural injury.
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PMID:Growth factors for human pleural mesothelial cells in soluble products from formed clots. 804 89

Clotting of human plasma by human alpha-thrombin was prolonged in the presence of haemoglobin as was human and bovine fibrinogen. Specifically, the clot time doubled for human plasma, human fibrinogen and bovine fibrinogen at 483, 233, and 116 microM haemoglobin, respectively. Fibrinopeptide A release was not inhibited at concentrations in approximately 16,000 molar excess compared with alpha-thrombin. Turbidometric analysis of fibrin polymerization showed a lengthening of the lag phase as well as the fibrin assembly process in the presence of haemoglobin. These findings suggested that neither fibrinogen recognition nor catalytic efficiency of thrombin was affected, implying that haemoglobin interferes with fibrin polymerization. Since human blood contains sufficient haemoglobin in erythrocytes to generate concentrations of up to 2.3 mM upon cell lysis, and haemoglobin concentrations of 0.16-0.48 mM caused 1.25 to two times longer clotting times in fresh human plasma, respectively, haemoglobin may act to modulate clot formation under conditions of haemolysis.
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PMID:Haemoglobin inhibition of fibrin polymerization and clotting. 818 Mar 34

Data on fibrinolysis in diabetes mellitus are still unclear, as is the role of hyperglycaemia on this topic and the possibility of any therapeutic intervention. In this study we examined fibrinopeptide A, tissue plasminogen activator and plasminogen activator inhibitor plasma levels in Type 1 diabetic patients compared to matched healthy normal controls, and the effect of induced hyperglycaemia on these parameters. At the same time the effect of a glycosaminoglycan, Sulodexide, administration during hyperglycaemia was evaluated. Fibrinopeptide A and plasminogen activator inhibitor were increased while tissue plasminogen activator was decreased in Type 1 diabetic patients, in the basal state. Induced hyperglycaemia increases fibrinopeptide A formation and tissue plasminogen activator concentrations, while it decreases plasminogen activator inhibitor levels more in normal subjects than in diabetic patients. Sulodexide consistently reduces this phenomenon. This study shows an altered fibrinolytic response to increased thrombin activation in Type 1 diabetic patients and suggests that the administration of the glycosaminoglycan, Sulodexide, may help to reduce this phenomenon.
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PMID:Impaired fibrinolytic response to increased thrombin activation in type 1 diabetes mellitus: effects of the glycosaminoglycan sulodexide. 833 53

Fibrinopeptide A (FPA) is a small polypeptide cleaved from fibrinogen by thrombin, has a short half-life, and is considered a sensitive biochemical marker of thrombin activity, fibrin generation, and ongoing thrombosis. Increased plasma levels of FPA have been reported in various procoagulable and thrombotic medical and cardiovascular disorders, including acute myocardial infarction, unstable angina, and sudden cardiac death. However, activation of thrombosis by the arterial injury incurred during coronary angioplasty has not been systematically examined with use of plasma FPA measurements. To detect and monitor activation of thrombosis by coronary angioplasty, plasma levels of FPA were obtained by venipuncture and measured by radioimmunoassay before, immediately after, 24 to 48 h later, and 1 and 3 months after uncomplicated coronary angioplasty. From December 1990 through June 1991, FPA was measured in 30 patients (28 men and 2 women, aged 54 +/- 9 years) with coronary artery disease who were undergoing coronary angioplasty. The mean left ventricular ejection fraction was 55 +/- 7%. The dilated vessel was the left anterior descending coronary artery in 20 patients (together with a second vessel in 2), the right coronary artery in 9, and the left circumflex in 1. The procedure was successful and free of major complications in all patients. Before angioplasty the FPA levels averaged 6.50 +/- 1.18 ng/ml. Shortly after angioplasty they rose to 20.20 +/- 7.91 ng/ml (p = 0.08) despite intravenous heparin. At 24 to 48 h and after heparin had been discontinued for at least 4 h, the mean FPA levels were significantly higher (32.33 +/- 10.86 ng/ml) compared with baseline values (p = 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma level changes of fibrinopeptide A after uncomplicated coronary angioplasty. 834 63


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