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 the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid, on the development of diabetes, insulin resistance, and abnormalities of blood coagulation in male WBN/Kob rats, a model of spontaneous diabetes mellitus. After 8-month oral EPA-E treatment, the incidence of diabetes at a dose of 0.1, 0.3, and 1.0 g/kg was 92%, 50%, and 17%, respectively. Its incidence was suppressed significantly and dose-dependently at a dose of 0.3 g/kg or higher compared with the rate (100%) for the vehicle control. Additionally, EPA-E significantly and dose-dependently decreased the elevation of plasma glucose after an oral glucose load and increased the glucose infusion rate (GIR) during the euglycemic insulin-glucose clamp test at a dose of 0.1 g/kg or higher compared with the vehicle control. Furthermore, EPA-E significantly and dose-dependently ameliorated coagulation-related parameters, including the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen level, and factor II, V, VII, VIII, IX, X, XI, and XII and antithrombin III (AT III) activities, and fibrinolysis-related parameters, including plasminogen, tissue-type plasminogen activator (t-PA), alpha2-plasmin inhibitor (alpha2-PI), and plasminogen activator inhibitor (PAI), and also suppressed ADP- or collagen-induced platelet aggregation and the cholesterol to phospholipid (C/P) molar ratio in platelet membranes at a dose of 0.1 g/kg or higher. These data demonstrate multiple actions of the product in these laboratory animals. These include changes in platelet function, coagulation/fibrinolysis factors, plasma immunoreactive insulin secretion, and plasma glucose/insulin resistance.
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PMID:Long-term administration of highly purified eicosapentaenoic acid ethyl ester prevents diabetes and abnormalities of blood coagulation in male WBN/Kob rats. 1091 4

Protein C is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C: APC) by thrombin in the presence of thrombomodulin. APC plays an important role in regulating coagulation and fibrinolysis by inactivating not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). The aim of the present study was to examine the effect of a human APC product (designated as CTC-111), compared with that of heparin, on the disseminated intravascular coagulation (DIC) induced by lipopolysaccharide (LPS) in rats. LPS (1 mg/kg/h) infusion was performed through a femoral vein for 4 h. One-fifth amount of the total dosage of CTC-111 or heparin was injected into the other femoral vein, followed by a 4-h infusion of the remainder. Both CTC-111 (10,000-100,000 U/kg) and heparin (400-800 IU/kg) inhibited the decrease in platelet count and fibrinogen level equally. The prolonged activated partial thromboplastin time and prothrombin time observed in DIC rats were further elongated in both CTC-111- and heparin-treated rats. But, this prolongation was less in CTC-111-treated rats than in the heparin-treated ones. Heparin inhibited the increase in fibrin and fibrinogen degradation products more prominently than CTC-111. On the other hand, CTC-111 strongly inhibited the increase in PAI-1 activity but heparin did not. These results suggest that CTC-111 may enhance fibrinolysis through its direct inhibitory effect on PAI-1. The parameters for liver or renal damage, i.e., plasma glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), creatinine (Cre) and blood urea nitrogen (BUN), were significantly increased by LPS infusion. Both CTC-111 (100,000 U/kg) and heparin (800 IU/kg) decreased the increase in GOT and GPT levels significantly, whereas neither affected the increase in Cre or BUN. From these results, the activation of the blood coagulation system might partially contribute to the progression of liver damage caused by LPS, and might be less involved in the progression of renal damage in this model. In conclusion, CTC-111 showed both anticoagulant and profibrinolytic activity in the LPS-induced DIC model without excessive prolongation of coagulation time. From these results, CTC-111 is expected to be a useful remedy for DIC without the risk of bleeding.
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PMID:Effect of activated human protein C on disseminated intravascular coagulation induced by lipopolysaccharide in rats. 1105 Jun 97

The influence of thyroid failure on haemostasis is controversial, both hypocoagulable and hypercoagulable states have been reported. Since both subclinical and overt hypothyroidism have been associated with atherosclerosis, a hypercoagulable state in addition might represent a risk factor for thromboembolic disease. We investigated various haemostatic variables in 42 women with subclinical hypothyroidism and compared them to 66 euthyroid controls. Prothrombin time, activated partial thromboplastin time, fibrinogen, factor VII activity (FVII:C), factor VII antigen (FVII:Ag), factor VIII activity, von Willebrand factor (vWF), antithrombin III, heparin cofactor II, protein C, protein S, plasminogen, antiplasmin, plasminogen activator inhibitor and tissue plasminogen activator, as well as common lipid variables, were measured. Factor VII:C (P < 0.02) and the ratio FVII:C/FVII:Ag (P < 0.01) were significantly increased in subclinical hypothyroid patients compared to the control group. Both parameters remained higher in hypothyroid patients after exclusion of 18 women on oestrogen replacement therapy. No differences were found between the groups with respect to vWF or the other haemostatic and lipid variables tested. Patients with subclinical hypothyroidism had significantly higher levels of FVII:C. The greater increase in FVII:C compared to that of FVII:Ag, as shown by the increase in their ratio, might reflect the presence of activated FVIIa. This might mean a hypercoagulable state, which could contribute to the increased prevalence of coronary heart disease reported in such patients. A hypercoagulable state might be another argument in favour of thyroxine replacement treatment in subclinical hypothyroidism, especially in patients with additional risk factors for vascular disease.
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PMID:Haemostatic profile in hypothyroidism as potential risk factor for vascular or thrombotic disease. 1116 51

Recent studies have focused on a myriad of mechanisms by which inflammation can potentiate blood clotting. Inflammatory mediators like endotoxin and tissue necrosis factor (TNF)-alpha can cause the expression of tissue factor on monocytes and, possibly, endothelium, thereby initiating the coagulation cascade. Activation of the complement system can lead to exposure of membrane surfaces capable of amplifying the initial tissue factor stimulus by facilitating the assembly of the factor VIIIa-factor IXa and the factor Xa-factor Va complexes. Inflammatory mediators, particularly interleukin-6, can also increase the levels of fibrinogen, an acute-phase reactant. In addition, the inflammatory mediators can elevate the levels of plasminogen activator inhibitor, thus suppressing the fibrinolytic system. These studies alone, however, do not prove that inflammation can trigger clinically relevant thrombus formation in vivo. For instance, TNF-alpha has been studied in cancer patients as a potential cure for cancer, and even though these patients are hypercoaguable, thrombosis was not commonly observed as a side effect of the near-lethal doses of TNF-alpha that were administered. Based on primate studies, inflammatory mediators like TNF-alpha can promote clot deposition effectively only if there is reduced flow and inhibition of the natural anticoagulant pathways. The requirement for multiple simultaneous injurious events probably explains why inflammation alone is not observed as a major cause of thrombosis.
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PMID:Does inflammation contribute to thrombotic events? 1125 39

This paper aimed to investigate the effect of lumbrokinase on the anticoagulation and fibrinolysis in treating cerebral infarction. Lumbrokinase was used in patients with cerebral infarction. Patients were randomly divided into treatment group (n = 31) and control group (n = 20). Single blind method was used in this investigation. The Chinese stroke score was used to evaluate the results of treatment before and after administration of lumbrokinase. Kaolin partial thromboplastin time (KPTT), prothrombin time (PT), fibrinogen content, vWF content were analyzed, and tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor (PAI) activity, D-dimer level were assayed. In both groups, the stroke score decreased after administration, but in the treatment group, it was more obvious. In the treatment group, KPTT was prolonged, t-PA activity and D-dimer level increased, while the content of fibrinogen decreased significantly. There were no significant changes of PT and PAI activity in both groups. It is concluded that lumbrokinase is beneficial to the treatment of cerebral infarction. The effect of lumbrokinase is related to the inhibition of intrinsic coagulation pathway and the activation of fibrinolysis via an increase of t-PA activity.
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PMID:Changes in coagulation and tissue plasminogen activator after the treatment of cerebral infarction with lumbrokinase. 1132 42

Aprotinin reduces blood transfusion requirements in orthotopic liver transplantation (OLT). Concern has been voiced about the potential risk for thrombotic complications when aprotinin is used. The aim of this study is to evaluate the effects of aprotinin on the two components of the hemostatic system (coagulation and fibrinolysis) in patients undergoing OLT. As part of a larger, randomized, double-blind, placebo-controlled study, we compared coagulation (fibrinogen level, activated partial thromboplastin time [aPTT], prothrombin time, and platelet count) and fibrinolytic variables (tissue-type plasminogen activator [tPA] antigen and activity, plasminogen activator inhibitor activity, and D-dimer), as well as thromboelastography (reaction time [r], clot formation time, and maximum amplitude) in 27 patients administered either high-dose aprotinin (2 x 10(6) kallikrein inhibitor units [KIU] at induction, continuous infusion of 1 x 10(6) KIU/h, and 1 x 10(6) KIU before reperfusion; n = 10), regular-dose aprotinin (2 x 10(6) KIU at induction and continuous infusion of 0.5 x 10(6) KIU/h; n = 8), or placebo (n = 9) during OLT. Blood samples were drawn at seven standardized intraoperative times. Baseline characteristics were similar for the three groups. During the anhepatic and postreperfusion periods, fibrinolytic activity (plasma D-dimer and tPA antigen levels) was significantly lower in aprotinin-treated patients compared with the placebo group. Interestingly, coagulation times (aPTT and r) were significantly more prolonged in aprotinin-treated patients than the placebo group. No difference was seen in the incidence of perioperative thrombotic complications in the entire study population (n = 137). Aprotinin has an anticoagulant rather than a procoagulant effect. Its blood-sparing (prohemostatic) effect appears to be the overall result of a strong antifibrinolytic and a weaker anticoagulant effect. These findings argue against a prothrombotic effect of aprotinin in patients undergoing OLT.
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PMID:Aprotinin in orthotopic liver transplantation: evidence for a prohemostatic, but not a prothrombotic, effect. 1167 89

Pigs are often used as animal models in research on blood coagulation and fibrinolysis. The usefulness of the assays applied within this field, and the knowledge of reference intervals are therefore essential and of utmost importance. In the study reported here, we investigated the applicability of commercial human coagulation and fibrinolysis assays for use with porcine plasma. In total, 22 functional and immunologic assays were applied to plasma obtained from domestic pigs, and the following blood coagulation and fibrinolysis variables were measured: prothrombin time, activated partial thromboplastin time, tissue factor, tissue factor pathway inhibitor, factor VII, protein C, protein S, prothrombin fragment 1+2, antithrombin, thrombin-antithrombin complexes, fibrinogen, soluble fibrin, urokinase-type plasminogen activator, plasmin inhibitor, plasminogen activator inhibitor 1, and D-dimer. We found that 11 of 12 functional assays, but only 3 of 10 immunoassays, were applicable to porcine plasma, and we determined the normal range of these variables. We conclude that human functional assays are useful in porcine plasma, whereas only a few immunologic assays can be used. However, precautions must be taken in interpretation of the results and in extrapolation toward human results because possible differences between porcine and human values can be due to species variations and/or methodologic errors.
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PMID:Usefulness of human coagulation and fibrinolysis assays in domestic pigs. 1190 Apr 11

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.
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PMID:Lonomia genus caterpillar envenomation: clinical and biological aspects. 1191 Jan 97

Sepsis and trauma are the two most common causes of disseminated intravascular coagulation and multiple organ dysfunction syndrome. Both disseminated intravascular coagulation and the systemic inflammatory response syndrome often lead to multiple organ dysfunction syndrome. The current studies have evaluated the relationship between the anaphylatoxin, C5a, and changes in the coagulation/fibrinolytic systems during the cecal ligation and puncture (CLP) model of sepsis in rats. CLP animals treated with anti-C5a had a much improved number of survivors (63%) compared to rats treated with pre-immune IgG (31%). In CLP rats treated with pre-immune IgG there was clearly increased procoagulant activity with prolongation of the activated partial thromboplastin time and prothrombin time, reduced platelet counts, and increased levels of plasma fibrinogen. Evidence for thrombin formation was indicated by early consumption of factor VII:C, subsequent consumption of factors XI:C and IX:C and anti-thrombin and increased levels of the thrombin-anti-thrombin complex and D-dimer. Limited activation of fibrinolysis was indicated by reduced plasma levels of plasminogen and increased levels of tissue plasminogen activator and plasminogen activator inhibitor. Most of these parameters were reversed in CLP rats that had been treated with anti-C5a. Production of C5a during sepsis may directly or indirectly cause hemostatic defects that can be reduced by blockade of C5a.
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PMID:Anti-c5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis. 1200 Jul 38

The pathophysiological basis of hemorrhage in dengue infections remains poorly understood, despite the increasing global importance of these infections. A large prospective study of 167 Vietnamese children with dengue shock syndrome documented only minor prolongations of prothrombin and partial thromboplastin times but moderate to severe depression of plasma fibrinogen concentrations. A detailed study of 48 children revealed low plasma concentrations of the anticoagulant proteins C, S, and antithrombin III, which decreased with increasing severity of shock, probably because of capillary leakage. Concurrent increases in the levels of thrombomodulin, tissue factor, and plasminogen activator inhibitor type 1 (PAI-1) indicated increased production of these proteins. Thrombomodulin levels suggestive of endothelial activation correlated with increasing shock severity, whereas PAI-1 levels correlated with bleeding severity. Dengue virus can directly activate plasminogen in vitro. Rather than causing true disseminated intravascular coagulation, dengue infection may activate fibrinolysis primarily, degrading fibrinogen directly and prompting secondary activation of procoagulant homeostatic mechanisms.
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PMID:Coagulation abnormalities in dengue hemorrhagic Fever: serial investigations in 167 Vietnamese children with Dengue shock syndrome. 1211 93


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