Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute exercise evokes a transient increase in procoagulant activity. We evaluated the effect of physical conditioning on the activation of the coagulation and fibrinolytic systems. Two groups of subjects of different aerobic endurance levels (athletes and controls with maximal oxygen uptake (VO2max) 68.4 and 52.6 ml kg-1 min-1, respectively), were tested at rest and after standardized exercise at 80% of their individual VO2max. There was a significant increase in prothrombinfragment 1 + 2 (F1 + 2) level among controls in response to standardized exercise (p < 0.05), whereas no significant difference in the level of F1 + 2 between athletes and controls at rest or in response to exercise was demonstrated. Tissue plasminogen activator (tPA) antigen level at rest was significantly lower in athletes compared to controls (p < 0.03). A significant increase was found in the tPA level after standardized exercise in both groups (p < 0.02), which was lower in athletes compared to controls (p < 0.05). There were no significant differences between athletes and controls in plasminogen activator inhibitor-1 (PAI-1) and thrombin antithrombin complex (TAT) levels at rest. Athletes had a significantly lower PAI-1 level than controls after exercise (p < 0.05). In conclusion, the present study suggests an increased activation of the coagulation system in response to exercise in controls only. It also suggests adaptive changes in fibrinolytic potential induced by physical conditioning, as demonstrated by the lower level of tPA at rest and the lower levels of tPA and PAI-1 after exercise in athletes compared to controls.
 ...
PMID:The effect of physical conditioning suggests adaptation in procoagulant and fibrinolytic potential. 933 Apr 38

Thrombin-activable fibrinolysis inhibitor (TAFI) is a recently described plasma zymogen that can be activated by thrombin to an enzyme with carboxypeptidase B-like activity. The enzyme, TAFIa, potently attentuates fibrinolysis. TAFI activation, like protein C activation, is augmented about 1250-fold by thrombomodulin (TM). In this work, the effects of both soluble and cellular forms of TM on TAFI activation-dependent suppression of fibrinolysis were investigated. Soluble TM included in clots formed from purified components, barium citrate-adsorbed plasma, or normal human plasma maximally increased the tissue plasminogen activator-induced lysis time 2-3-fold, with saturation occurring at 5, 10, and 1 nM TM in the three respective systems. Soluble TM did not effect lysis in the system of purified components lacking TAFI or in plasmas immunodepleted of TAFI. In addition, the antifibrinolytic effect of TM was negated by monoclonal antibodies against either TAFI or TM. The inhibition of fibrinolysis by cellular TM was assessed by forming clots in dialyzed, barium citrate-adsorbed, or normal plasma over cultured human umbilical vein endothelial cells (HUVECs). Tissue plasminogen activator-induced lysis time was increased 2-fold, with both plasmas, in the presence of HUVECs. The antifibrinolytic effect of HUVECs was abolished 66% by specific anti-TAFI or anti-TM monoclonal antibodies. A newly developed functional assay demonstrated that HUVECs potentiate the thrombin-catalyzed, TM-dependent formation of activated TAFI. Thus, endothelial cell TM, in vitro at least, appears to participate in the regulation of not only coagulation but also fibrinolysis.
 ...
PMID:Both cellular and soluble forms of thrombomodulin inhibit fibrinolysis by potentiating the activation of thrombin-activable fibrinolysis inhibitor. 944 87

We investigated annexin V expression and membrane vesiculation during activation of four leukemic cell lines (U937, HL60, HEL, and CMK11-5) in order to determine whether annexin V had a role in the coagulation abnormalities related to malignancy. After stimulation by tissue plasminogen activator, binding of a monoclonal anti-annexin V antibody to U937 cells and HL60 cells increased in comparison with binding to control cells. Stimulation with thrombin or lipopolysaccharide also induced such an increase, but U46619 did not. Following activation of U937 and HL60 cells with thrombin and lipopolysaccharide, microparticle formation increased. Tissue plasminogen activator caused an increase of microparticles in U937 cells, but not HL60 cells. On the other hand, CMK11-5 and HEL cells did not show any increase of microparticles. These results suggest that some agonists can potently stimulate expression of prothrombinase
 ...
PMID:Annexin V expression and membrane vesiculation during activation of leukemic cell lines. 973 Nov 6

BACKGROUND: Previous work has demonstrated that ruptured abdominal aortic aneurysm (AAA) is associated with systemic thrombin generation and inhibition of systemic fibrinolysis. The procoagulant and hypofibrinolytic state associated with ruptured AAA predisposes to microvascular and macrovascular thrombosis and subsequent myocardial injury. The aim of this study was to determine the relationship between haemostatic derangement and biochemical evidence of myocardial injury in patients operated on for ruptured AAA. METHODS: Ten patients undergoing repair of ruptured AAA were studied. Tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor (PAI) activity, prothrombin fragment (PF) 1 + 2, D-dimer and fibrinogen levels were measured before operation, and immediately before and 5 min after aortic clamp release. Plasma levels of cardiac troponin (cTn) I were measured before operation, and 6 and 24 h after aortic clamp release. RESULTS: There was no relationship between tPA activity, PF 1 + 2, D-dimer or fibrinogen and cTn-I levels at any sampling point. There was, however, a significant positive correlation (Spearman rank test) between PAI activity immediately before (median 38.6 (range 13.0-39.4) units ml-1) and 5 min after (37.2 (10.6-39.4) units ml-1) aortic clamp release, and cTn-I at 6 h (median 3.17 (range less than 0.5 to 71.1) ng ml-1) and 24 h (5.55 (range less than 0.5 to 110) ng ml-1) after aortic clamp release. CONCLUSION: These data strongly support the hypothesis that the inhibition of systemic fibrinolysis which occurs in response to ischaemia and reperfusion during ruptured AAA repair contributes to the development of subsequent myocardial injury.
 ...
PMID:Vascular surgical society of great britain and ireland: inhibition of systemic fibrinolysis is associated with myocardial injury in patients operated on for ruptured abdominal aortic aneurysm 1036 22

Evidence suggests that isolated intracranial hypertension (iIH) is often associated with cerebral venous thrombosis (CVT). In eight patients referred to our Institution for iIH who were later shown to harbor CVT we have performed a comprehensive coagulation work-up, including genetic tests for inherited predisposition to thrombophilia, to clarify the etiology of sinus venous thrombosis. All subjects were women. All but one were overweight. There were high plasma concentrations of D dimer, thrombin-anti-thrombin complexes or prothrombin fragments 1 and 2, further supporting the neuroimaging diagnosis of CVT. Importantly, seven of eight cases had a raised level of plasminogen activator inhibitor 1, a well known inhibitor of fibrinolysis related to obesity. Tissue plasminogen activator levels were elevated accordingly. Factor V gene mutation was present in one subject, and the 20,210 prothrombin gene mutation was found in another individual. Three patients had elevated plasmatic levels of homocysteine. In conclusion, the present study provides solid evidence that impaired fibrinolysis probably related to overweight, acting in concert with other prothrombotic abnormalities, is involved in the pathogenesis of CVT presenting as iIH.
 ...
PMID:A hypofibrinolytic state in overweight patients with cerebral venous thrombosis and isolated intracranial hypertension. 1063 43

Previous studies have shown that thrombin generation in vivo caused a 92% decrease in factor IX (F.IX) activity and the appearance of a cleavage product after immunoblotting that comigrated with activated F.IX (F.IXa). Under these conditions, the fibrinolytic system was clearly activated, suggesting plasmin may have altered F.IX. Thus, the effect(s) of plasmin on human F.IX was determined in vitro. Plasmin (50 nM) decreased the 1-stage clotting activity of F.IX (4 microM) by 80% and the activity of F.IXa (4 microM) by 50% after 30 minutes at 37 degrees C. Plasmin hydrolysis of F.IX yields products of 45, 30, 20, and 14 kd on reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and 2 products of 52 and 14 kd under nonreducing conditions. Plasmin-treated F.IX did not bind the active site probe, p-aminobenzamidine, or form an SDS-stable complex with antithrombin. It only marginally activated human factor X in the presence of phospholipid and activated factor VIII. Although dansyl-Glu-Gly-Arg-chloromethyl ketone inactivated-F. IXa inhibited the clotting activity of F.IXa, plasmin-treated F.IX did not. Plasmin cleaves F.IX after Lys43, Arg145, Arg180, Lys316, and Arg318, but F.IXa is not appreciably generated despite cleavage at the 2 normal activation sites (Arg145 and Arg180). Tissue plasminogen activator-catalyzed lysis of fibrin formed in human plasma results in generation of the 45- and 30-kd fragments of F.IX and decreased F.IX clotting activity. Collectively, the results suggest that plasmin is able to down-regulate coagulation by inactivating F.IX.
 ...
PMID:Proteolytic processing of human coagulation factor IX by plasmin. 1064 7

We studied 67 healthy women who were randomly allocated to receive third generation gestodene (Gynera) or second generation levonorgestrel (Microgynon 30) combination of low-dose estrogen oral contraceptives (OCs) for their hemostatic effects over 2 years. Hemostatic changes were apparent within 3 months of OC use. Hematocrit (Hct) was not affected, but hemoglobin (Hb) concentration decreased by 18 months. Shortened prothrombin time (PT) and activated plasma thromboplastin time (APTT) were associated with elevated fibrinogen within the 12-month use of both OCs. Factor VII was reduced only in Micro 30 during the 18 months of use. Enhanced thrombin-antithrombin (TAT)-complex level was seen at 18 months of Gynera use. Prothrombin fragment1+2 (F1+2) rise was seen at 3 months with Micro 30. Reduced antithrombin III (ATIII) activity was seen at 18 months with Gynera and at 24 months with Micro 30. Increased protein C activity was seen at 3 months and reduced protein S occurred at 18 months of Gynera use. Tissue plasminogen activator (t-PA) activity was enhanced for 6 months in both OCs with raised D-dimer levels for 12 months with Gynera and 6 months with Micro 30. Decreased t-PA antigen was seen at 18 months and decreased urokinaselike plasminogen activator (u-PA) antigen occurred throughout the 24 months of both OCs use. Enhanced u-PA activity was only seen in Gynera users. Elevated plasminogen levels were apparent throughout both OCs use. PAI-1 levels were significantly decreased with Micro 30. With Gynera, the decreased PAI-1 activity was seen only at 18 months and PAI-1 antigen at 12 months. No change in platelets and von Willebrand factor (vWF) were seen in long-term OC use except that beta-thromboglobulin (beta-TG) showed decreased trends reaching statistical significance by 18 and 24 months of Micro 30 use and by 24 months of Gynera use. A further significant decrease in beta-TG, u-PA antigen, ATIII, and protein S levels were seen 3 months after pill stoppage compared with pretreatment levels. Activated protein C resistance (APCR) was negative in all subjects before and during OC use. The study indicated dynamic balance between coagulation and fibrinolysis with no endothelial activation. However, because some hemostatic markers showed wide fluctuations during OC use, a longer term study is warranted to investigate any adverse hemostatic changes that might enhance the risks of venous thromboembolism in Asian subjects known to be less prone to thrombosis.
 ...
PMID:Effects on hemostasis after two-year use of low dose combined oral contraceptives with gestodene or levonorgestrel. 1072 85

Current therapy of acute coronary syndromes (i.e., unstable angina and non-Q-wave myocardial infarction, Q-wave myocardial infarction) consists of thrombolytic, anti-platelet, and anti-coagulant therapy. In most cases of acute coronary syndromes, the pathogenesis is a mural thrombus formation on a ruptured or eroded atherosclerotic plaque. Both platelets and thrombin play an essential role in the pathophysiology of acute coronary syndromes. Aspirin and heparin are essential treatments for patients with acute coronary syndromes. Novel thrombin and platelet inhibitors have been developed and demonstrated useful effects for improving both acute and long-term clinical outcomes in acute coronary syndromes. Tissue plasminogen activator is the compound for effective thrombolytic therapy. New developments like reteplase and TNK-tPA can be administered as bolus injection and result in rapid reperfusion. Combination of thrombolytic therapy and glycoprotein IIb/IIIa inhibitors seem to accelerate and improve reperfusion. Clopidogrel as anti-aggregatory compound demonstrated profound effects following stent implantation as well as in patients with aspirin intolerance. Administration of glycoprotein IIb/IIIa inhibitors like abciximab, eptifibatide, tirofiban results in reduction of cardiovascular events in patients with unstable angina and following coronary intervention. Low-molecular-weight heparins like enoxiparin and dalteparin seem to be more effective than heparin, and their use is evolving in patients with unstable angina. Anti-thrombin therapy with hirudin results in slight reduction of cardiovascular events in combination with tolerable safety profile. It has yet to be determined which combination of agents and procedural strategies most significantly reduces mortality and serious events in patients with acute coronary syndromes.
 ...
PMID:Antithrombotic therapy in acute coronary syndromes. 1099 90

Persons who have been in contact with Lonomia achelous or Lonomia obliqua caterpillars present external and internal bleeding and opening of recently healed wounds. Hematological tests show normal platelet count, prolonged prothrombin time, activated partial thromboplastin time and thrombin time, totally corrected by normal plasma. Decreased fibrinogen (Fg), factor (F) V, FXIII, plasminogen and alpha(2)-antiplasmin with increased FVIII: C, von Willebrand factor, Fg degradation products and D dimers. Tissue plasminogen activator, plasminogen activator inhibitor and protein C varied. In L. achelous biological fluids, compounds with anticoagulant or procoagulant properties have been identified. In L. obliqua bristle extracts, mainly procoagulant activities have been identified. Subcutaneous injections of L. achelous crude extracts and a semipurified fraction reduce Fg, plasminogen and FXIII in rabbits. Intravenous injections of a very purified fraction of L. achelous in rabbits produce lysis of preformed thrombi, a decrease of Fg, plasminogen, alpha(2)-antiplasmin, FXIII and inhibition of postthrombolytic thrombus growth. Subcutaneous injections of L. obliqua bristle extracts prolong prothrombin time and activated partial thromboplastin time and reduce FXIII. Intravenous injections of crude bristle extract and a purified fraction of L. obliqua induce disseminated intravascular coagulation.
 ...
PMID:Lonomia genus caterpillar envenomation: clinical and biological aspects. 1191 Jan 97

We investigated the effect of a high walnut and cashew diet on haemostatic variables in people with the metabolic syndrome. Factor analysis was used to determine how the haemostatic variables cluster with other components of the metabolic syndrome and multiple regression to determine possible predictors. This randomized, control, parallel, controlled-feeding trial included 68 subjects who complied with the Third National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol criteria. After a 3-week run-in following the control diet, subjects were divided into three groups receiving either walnuts or cashews (20 energy%) or a control diet for 8 weeks. The nut intervention had no significant effect on von Willebrand factor antigen, fibrinogen, factor VII coagulant activity, plasminogen activator inhibitor 1 activity, tissue plasminogen activator activity or thrombin activatable fibrinolysis inhibitor. Statistically, fibrinogen clustered with the body-mass-correlates and acute phase response factors, and factor VII coagulant activity clustered with high-density lipoprotein cholesterol (HDL-C). Tissue plasminogen activator activity, plasminogen activator inhibitor 1 activity and von Willebrand factor antigen clustered into a separate endothelial function factor. HDL-C and markers of obesity were the strongest predictors of the haemostatic variables. We conclude that high walnut and cashew diets did not influence haemostatic factors in this group of metabolic syndrome subjects. The HDL-C increase and weight loss may be the main focus of dietary intervention for the metabolic syndrome. Furthermore, diet composition may have only limited effects if weight loss is not achieved.
 ...
PMID:Clustering of haemostatic variables and the effect of high cashew and walnut diets on these variables in metabolic syndrome patients. 1609 34


<< Previous 1 2 3 4 Next >>