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:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated hemostatic parameters in a prospective study of 16 patients who received bone marrow transplants (BMT). We found a significant rise in the levels of fibrinogen, plasmin-alpha2 antiplasmin inhibitor complex, tissue-plasminogen activator.plasminogen activator inhibitor complex (t-PA.PAI), von Willebrand factor antigen, and thrombomodulin on day 14 after transplant compared with values before transplant. Protein C and thrombin-antithrombin III levels did not change significantly. No significant changes in prothrombin time ratio, activated partial thromboplastin time, or protein S were detected. Patients who had grades II-IV graft-versus-host disease (GVHD) (n = 6) showed a significantly higher level of t-PA.PAI on day 14 compared with those with grades 0-I GVHD (n = 10) (P = 0.0062). Three patients with grades II-IV GVHD developed thrombotic microangiopathy (TMA) on days 19, 19 and 62. In these patients, we noted significantly lower levels of fibrinogen (P = 0.0383), and significantly higher levels of t-PA.PAI (P = 0.0008) and thrombomodulin (P = 0.0001) on day 14 compared with those patients who did not develop TMA. These results suggest that prothrombotic states and endothelial damage may be caused by the conditioning regimen and/or acute GVHD during BMT; thrombomodulin values on day 14 post BMT may be useful in surveillance for TMA because of endothelial cell injury.
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PMID:Diagnostic value of hemostatic parameters in bone marrow transplant-associated thrombotic microangiopathy. 957 11

1. Elevated plasminogen activator inhibitor 1 (PAI-1) is a risk factor for thrombosis, and inhibitors of the interaction between PAI-1 and tissue plasminogen activator (t-PA) have antithrombotic and prothrombolytic activity in animals. We describe the antithrombotic effects in the rat of a monoclonal antibody (MA33H1) which converts PAI-1 to a non-inhibitory substrate. 2. The activity of MA33H1 against rat PAI-1 was confirmed using two-chain t-PA and a chromogenic substrate. MA33H1 was evaluated in rat venous (thromboplastin + stasis in the abdominal vena cava) and arterial (electric current applied to a carotid artery) thrombosis models. The effects on tail-transection bleeding time were studied. 3. MA33H1 at 100 ng ml(-1) inhibited both human (44.1%) and rat PAI-1 (49.7%). This effect was concentration-dependent. Its effect on human PAI-1 was not significantly inhibited by 1 microg ml(-1) fibrin or a approximately 7 fold molar excess of vitronectin (1 nM). Inhibition of rat PAI-1 was unchanged by fibrin, but vitronectin reduced inhibition from 0.5 nM. 4. In the venous thrombosis model, MA33H1 significantly reduced thrombus weights by 38 and 58.6% at 50 and 100 microg kg(-1) min(-1) i.v. respectively. This effect was inhibited by tranexamic acid. In the arterial model, MA33H1 significantly increased the delay to occlusive thrombus formation by 58 and 142% at 50 and 100 microg kg(-1) min(-1) i.v., and did not affect bleeding time at 300 microg kg(-1) min(-1) i.v. 5. Thus, a monoclonal antibody which transforms PAI-1 to a t-PA substrate prevents thrombus formation in the rat with no effect on bleeding time at a higher dose.
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PMID:Antithrombotic activity of a monoclonal antibody inducing the substrate form of plasminogen activator inhibitor type 1 in rat models of venous and arterial thrombosis. 977 40

Twenty patients with recently recognised bronchial asthma and 22 age and sex-matched healthy control subjects were studied. In both groups the activated partial thromboplastin time (APTT), prothrombin ratio (INR), fibrinogen, euglobulin lysis time (ELT), platelet number and platelet adhesion and aggregation, tissue plasminogen activator antigen (t-PA Ag) and activity of plasminogen activator inhibitor (PAI-1) were tested and compared. Statistically significant differences between asthmatic and control groups concerning adhesion, aggregation, APTT and ELT were found. In asthmatic group after 14 days of prednisone administration in a dose of 20 mg/d statistically significant (p < 0.05) shortening of APTT, and a significant increase of adhesion, aggregation and PAI-1 activity were found. These results suggest that in asthmatic patients after prednisone treatment platelet activity appeared in a form of intensification of adhesion and of aggregation degree, also the activity of PAI-1 probably of the platelet origin increased.
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PMID:[Changes in platelet function, activated partial thromboplastin time and plasminogen activator inhibitor in patients with bronchial asthma after prednisone treatment]. 985 61

The effect of alcohol ingestion before exercise on blood haemostasis is not known. The present study examined the effects of moderate alcohol ingestion on blood haemostatic variables at rest and in response to exercise. Eleven normal healthy individuals randomly performed two tests separated by 7 days. A moderate dose of ethanol (0.5 g.kg-1) was administered before one test, whereas an equal volume of an alcohol-free drink was administered before the other. Forty-five minutes after the ingestion of either drink, the participants cycled at 65% VO2max for 30 min followed by a 5-min all-out performance. Venous blood samples were obtained before and 45 min after the ingestion of both drinks, and also immediately after exercise. Exercise induced a significant increase in tissue-type plasminogen activator activity and antigen, and factor VIII procoagulant activity. The post-exercise data also showed a significant decrease in plasminogen activator inhibitor activity and soluble fibrin, with a significant shortening in prothrombin time and activated partial thromboplastin time, but not thrombin time. No significant changes were observed in antithrombin III. Although no significant differences were found between trials in the haemostatic and fibrinolytic variables at rest, a significant decrease in fibrinogen concentration was observed after exercise in the alcohol trial. This suggests that ingesting a moderate dose of alcohol does not alter blood coagulation and fibrinolysis at rest. Apart from fibrinogen concentration, which was significantly decreased after exercise in the alcohol trial, most of the haemostatic and fibrinolytic variables were not affected by alcohol. The mechanism responsible for the decrease in fibrinogen following exercise in the alcohol trial remains unknown, but might be related to inhibition of fibrinogen synthesis by the liver or an enhanced rate of its catabolism.
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PMID:The effect of moderate alcohol ingestion on blood coagulation and fibrinolysis at rest and in response to exercise. 1040

Survival of the implanting human blastocyst requires that trophoblasts gain access to the maternal circulation. This is initially achieved when syncytiotrophoblasts breach endometrial capillarlies and venules. Subsequently, extravillous cytotrophoblasts penetrate the spiral arteries to induce their morphological transformation into high-flow, low-resistance vessels. This process provides the embryo with a requisite source of oxygen and nutrients, but risks decidual hemorrhage leading to abortion and abruption. Endovascular trophoblast invasion occurs within a matrix of decidualizing endometrial stromal cells. These decidual cells are temporally and spatially positioned to create a local hemostatic milieu which can counteract the threat of hemorrhage. Prior studies from our laboratory have established that decidual cells of luteal phase and pregnant endometrium express two crucial modulators of hemostasis: 1) tissue factor (TF), the primary initiator of hemostasis via factor Xa activation; and 2) plasminogen activator inhibitor type 1 (PAI-1), the fast inhibitor of the primary fibrinolytic agent, tissue type plasminogen activator. This coordinate increase in TF and PAI-1 expression provides a mechanism by which decidual cells control local hemostasis during endovascular trophoblast invasion. Cultures of human endometrial stromal cells and decidual cells isolated from first trimester endometrium demonstrate that progestins enhance TF and PAI-1 protein and mRNA expression via the induction of crucial intermediate transcription factors. Integration of these in vivo observations and in vitro studies suggest a model by which decidua acts to maintain hemostasis during implantation and placentation.
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PMID:The decidua regulates hemostasis in human endometrium. 1040 75

Treatment with intravenous recombinant human interleukin-2 (rh IL-2) is frequently accompanied by the capillary leak syndrome and disturbances of the coagulation system. Although the exact mechanisms are still not fully understood, the involvement of the endothelium is proven. This investigation aimed to elucidate more precisely the role of the endothelium in the generation of IL-2-based side-effects. In nine tumour patients receiving intravenous rh IL-2, parameters characterizing endothelial cell activation as well as activation of the coagulation system were evaluated. A significant increase of the circulating endothelial leucocyte adhesion molecule-1 (cELAM-1) and the vasoconstrictor peptide endothelin-1 (ET-1) was observed (P<0.05), indicating activation of endothelial cells. The simultaneous increase of tissue-plasminogen activator and plasminogen activator inhibitor type-1 during therapy (P<0.05) corroborated this observation. A decrease in platelet count parallelled by an increase of fibrin degradation products, the prolongation of partial thromboplastin time, and the decrease of fibrinogen (P<0.05) suggested the development of disseminated intravascular coagulation (DIC), induced by activated endothelium and intensified by transient hepatic failure. We concluded that activation of the endothelium mediated by IL-2 was accompanied by a loss of endothelial integrity and capillary leak. The activated endothelium can trigger DIC via activation of the coagulation cascade. The increased ET-1 might act as an endogenous counter-regulator of the disadvantageous haemodynamic side-effects induced by IL-2.
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PMID:Activation of endothelium by immunotherapy with interleukin-2 in patients with malignant disorders. 1055

We studied the short- and long-term histological responses induced by conventional and modified electronically detachable coils (GDCs) in experimental aneurysms. Eighteen carotid bifurcation aneurysms were produced microsurgically in rabbits. Six animals each were treated either with conventional or with GDCs coated with a mixture of tissue-thromboplastin to enhance intra-aneurysmal thrombus formation and of plasminogen activator inhibitor type-1 (PAI-1) in inhibit intra-aneurysmal clot fibrinolysis. Six served as untreated controls. Follow-up angiograms were obtained immediately and at 3, 6, 9, 12, 17, and 24 weeks after embolization prior to sacrifice of the animals. All aneurysms were studied macroscopically and histopathologically with the coils in situ. Five of six control aneurysms remained patent. Endovascular occlusion rates between > 90% and 100% were achieved in nine of twelve coiled aneurysms. Follow-up angiography demonstrated recanalization and coil compaction in 5 of them. Gross and microscopic histopathological examination revealed a membrane covering the orifice, intra-aneurysmal scar formation, and development of a neo-intima in both treatment groups at 17 and 24 weeks postembolization. The granulation tissue response appeared to be equally distributed in aneurysms treated with either uncoated or coated coils. Further quantitative morphometric studies are needed to prove if a thrombogenic/antithrombolytic coil-coating might be of value in providing a more enduring anatomic result after GDC-treatment of human brain aneurysms.
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PMID:Histopathological findings in experimental aneurysms embolized with conventional and thrombogenic/antithrombolytic Guglielmi coils. 1066 19

Formation of the blood clot is a slow but normal physiological process occurring as a result of the activation of blood coagulation pathways. Nature's guard against unwanted blood clots is the fibrinolytic enzyme system. In healthy people, there is a delicate dynamic balance between blood clot formation and blood clot dissolution. Available evidence suggests that exercise and physical training evoke multiple effects on blood hemostasis in normal healthy subjects and in patients. A single bout of exercise is usually associated with a transient increase in blood coagulation as evidenced by a shortening of activated partial thromboplastin time (APTT) and increased Factor VIII (FVIII). The rise in FVIII is intensity dependent and continues into recovery. The effects of acute exercise on plasma fibrinogen have yielded conflicting results. Thus, the issue of whether exercise-induced blood hypercoagulability in vitro mirrors an in vivo thrombin generation and fibrin formation remains disputable. Exercise-induced enhancement of fibrinolysis has been repeatedly demonstrated using a wide range of exercise protocols incorporating various exercise intensities and durations. Moderate exercise appears to enhance blood fibrinolytic activity without a concomitant activation of blood coagulation mechanisms, whereas, very heavy exercise induces simultaneous activation of blood fibrinolysis and coagulation. The increase in fibrinolysis is due to a rise in tissue-type plasminogen activator (tPA) and decrease in plasminogen activator inhibitor (PAI). The mechanism of exercise-induced hyperfibrinolysis is poorly understood, and the physiological utility of such activation remains unresolved. Strenuous exercise elicits a transient increase in platelet count, but there are conflicting results concerning the effect of exercise on platelet aggregation and activation. Few comprehensive studies exist concerning the influence of exercise training on blood hemostasis, making future investigation necessary to identify whether there are favorable effects of exercise training on blood coagulation, fibrinolysis, and platelet functions.
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PMID:Blood hemostasis in exercise and training. 1079 81

Total fibrinolytic activity in the vasculature is finely tuned by the balance between tissue plasminogen activator and plasminogen activator inhibitor type 1 (PAI-1). Although PAI-1 targets plasminogen activators, it also reacts with other serine proteases such as thrombin and factor Xa. The latter was shown to interact with PAI-1 only when a physiological concentration of calcium ions (Ca++) is present. Through such interaction, thrombin and Ca++-bound factor Xa shortened fibrin clot lysis times in a purified system by neutralizing PAI-1 activity. Both unfractionated heparin and vitronectin were shown to enhance the clot lysis further. Together with the cleavage and inactivation of PAI-1 by human neutrophil elastase, which was reported previously from our laboratory, such neutralization of PAI-1 activity by these serine proteases was shown to be strongly involved in the coagulation-associated enhancement of fibrinolytic activity.
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PMID:Coagulation-associated enhancement of fibrinolytic activity via a neutralization of PAI-1 activity. 1080 80

We investigated the age-related changes in blood coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats, animals that exhibit spontaneously diabetes mellitus at more than 6 months of age. The rats aged 6 months or more showed significant hyperglycemia, hypoinsulinemia, and hyperlipidemia. As changes in coagulation parameters, the data indicated significant increases in factors II, V, VII, VIII, IX, X, and XII activities; a significant decrease in antithrombin III activity in rats more than 6 months of age; significant increases in fibrinogen level and factor XI activity; and significant decreases in prothrombin time and activated partial thromboplastin time in those more than 9 months of age. As changes in fibrinolytic parameters, the animals showed significant decreases in plasminogen and tissue-type plasminogen activator, and significant increases in alpha2-plasmin inhibitor and plasminogen activator inhibitor at more than 6 months of age. In addition, there were significant correlations between the plasma levels of coagulation/fibrinolytic markers and the 4-hour fasting glucose or lipids. Furthermore, they displayed significant increases in ADP- or collagen-induced platelet aggregation and in cholesterol/phospholipid molar ratio in platelets at more than 9 months of age. The increase in cholesterol/phospholipid ratio may be responsible for hyperaggregation of platelets in diabetic animals. These findings suggest that WBN/Kob rats are suitable for research on blood coagulation abnormalities in diabetes. However, further studies are needed to clarify the details of the mechanisms involved.
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PMID:Age-related changes in coagulation, fibrinolysis, and platelet aggregation in male WBN/Kob rats. 1089 50


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