Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endotoxemia was evoked by bolus injection of Escherichia coli endotoxin (2 ng/kg body weight) in six healthy subjects to investigate the early kinetics of cytokine release in relation to the development of clinical and hematologic abnormalities frequently seen in gram-negative septicemia. The plasma concentration of tumor necrosis factor (TNF) increased markedly after 30 to 45 minutes, and reached a maximal level after 60 to 90 minutes. In each volunteer, the initial increase of plasma interleukin 6 (IL-6) concentrations occurred 15 minutes after the initial TNF increase, and maximal IL-6 concentrations were reached at 120 to 150 minutes. A transient increase in body temperature and pulse rate occurred simultaneously with the initial TNF and IL-6 increases, whereas a significant decrease in blood pressure occurred after 120 minutes. These changes were proportional to the changes in TNF and IL-6 concentrations. Coagulation activation, as assessed by a rise of prothrombin fragments and thrombin-antithrombin III complexes, was noted after 120 minutes, in the absence of activation of the contact system. A two- to sixfold increase in the concentrations of tissue plasminogen activator (t-PA) and von Willebrand factor antigen indicated endothelial cell activation. This increase started at 120 and 90 minutes, respectively. The release of t-PA coincided with activation of the fibrinolytic pathway, as measured by plasmin-alpha 2-antiplasmin complexes. The fibrinolytic activity of t-PA was subsequently offset by release of plasminogen activator inhibitor, observed 150 minutes after the endotoxin injection, and reaching a peak at 240 minutes. No complement activation was detected. These results show that in humans endotoxin induces an early, rapidly counteracted fibrinolytic response, and a more long-lasting activation of thrombin by a mechanism other than contact system activation. In addition, our data suggest that endotoxin-induced leukopenia and endothelial cell activation are mediated by TNF.
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PMID:Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. 212 34

Thrombin, plasmin and tissue plasminogen activator (one- and two-chain forms) were examined with respect to their reaction with the suicide substrate, 3,4-dihydro-3-benzyl-6-chloromethylcoumarin, at 4 degrees C. The enzymes were irreversibly inhibited and the apparent second-order rate constants ki/Ki were 31,000, 316, 187 and 250 M-1.s-1, respectively. The extent of fibrin clot lysis induced by urokinase and two-chain tissue plasminogen activator was considerably decreased after treatment of these enzymes with the dihydrocoumarin derivative (molar excess of inhibitor over enzyme ranging from 6 to 21 for urokinase and 50 to 1500 for tissue plasminogen activator). This inhibitor has been tested as anticoagulant in human plasma and was effective at prolonging the prothrombin time from 12 to 40 s.
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PMID:Reaction of thrombin and proteinases of the fibrinolytic system with a mechanism-based inhibitor, 3,4-dihydro-3-benzyl-6-chloromethylcoumarin. 213

Various parameters of the haemostatic and, more importantly, of the fibrinolytic systems were examined in 5 patients with severe pre-eclampsia/eclampsia. All 5 showed signs of haemolysis, elevated liver enzymes and low platelet count (HELLP syndrome). A significant decrease in platelet count (46.4 X 10(9)/litre) and an increase in beta-thromboglobulin (137 ng/ml) were observed in the HELPP patients in comparison with normal pregnant women (267 X 10(9)/litre and 49.3 ng/ml, respectively). No significant differences in fibrinogen levels, activated partial thromboplastin time, prothrombin time and fibrin(ogen) degradation products between the HELLP patient group and the normal pregnant group were observed. However, the antigenic levels of tissue-type plasminogen activator and type 1 plasminogen activator inhibitor were significantly higher in the HELLP pre-eclamptic women than in gestational age-matched controls. In contrast, the antigen levels of type 2 plasminogen activator inhibitor were significantly lower in the patients. These results indicate that platelet activation and alterations in plasminogen activator inhibitors type 1 and type 2 may be involved in the pathophysiological pathway of this syndrome.
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PMID:Clinical and haemostatic parameters in the HELLP syndrome: relevance of plasminogen activator inhibitors. 214 63

Patients with acute myeloid leukemia have multiple hemostatic and thrombotic complications, which may or may not result from disseminated intravascular coagulation. Previous studies incorporating routine coagulation analyses failed to detect any clinically useful information in most of these patients. In this study, the first comprehensive evaluation of the various aspects of the hemostatic system in a population of patients with acute myeloid leukemia was performed. Eighteen patients (23-71 years of age) were studied at either diagnosis or relapse. Hemostatic studies were performed at onset and on days 3, 7, and 30 after initiation of therapy. The bone marrow blast counts ranged from 8% to 98%; prothrombin time and activated partial thromboplastin time showed only minor prolongations in a few of these patients. However, in all patients measurement of platelet-associated markers revealed elevated platelet factor 4 and thromboxane B2 and normal 6-keto-prostaglandin F1 alpha levels. Fibrinolytic markers showed an increase in D-dimer and tissue plasminogen activator and a decrease in alpha 2-antiplasmin levels. Plasminogen, plasminogen activator inhibitor, and fibrinogen levels were normal. Coagulation markers demonstrated a decrease in protein C and antithrombin III levels and an elevation of the thrombin-antithrombin complex. The pretreatment values for all hemostatic markers studied were similar to the values obtained on days 3, 7, and 30 during treatment. This investigation demonstrated a subclinical activation of the components of the hemostatic system possibly leading to a hypercoagulable state. Although only six patients (33%) experienced hemorrhagic complications, the risk of bleeding and/or thrombosis was strongly evident in all patients. The significance of finding abnormal levels of specific molecular markers of hemostasis will be established in the future application of such markers in clinical evaluations of leukemic patients known to be at risk for coagulation disorders.
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PMID:Global and molecular hemostatic markers in acute myeloid leukemia. 222 Jun 67

This study, including 33 consecutive patients was designed to assess the haemostatic alterations occurring during repair of thoracoabdominal aneurysms. The surgical procedure consisted in Dacron graft replacement of the diseased aorta, using neither cardiopulmonary bypass, nor any shunting technique, nor any heparin. Blood samples were drawn before anaesthesia, before and 30 min after unclamping, and on the first postoperative day. The measured parameters were: haematocrit, platelet count, bleeding, activated cephalin, thrombin and prothrombin times, and concentrations of fibrinogen, factors V, VII, X and II, anti-thrombin III, proteins C and S, fibrin degradation products, D-dimers, alpha 2-antiplasmin, plasminogen, tissue plasminogen activator, plasminogen activator inhibitor, and serum protein. Eight patients developed severe multiple haemorrhages; 3 of them died during the procedure because of uncontrollable bleeding. Although the measured parameters were similar in the "bleeding" and control (n = 25) groups before surgery, there was, before unclamping in the first group, an important increase in activated cephalin and thrombin times, with a fall in concentrations of factor II and V, protein C, fibrinogen, and alpha 2-antiplasmin, and in platelet numbers. After unclamping, these changes worsened further, with an increase in prothrombin time and in fibrinogen levels (0,8 g.l-1), without any increase in fibrin degradation products. Abnormal bleeding started about 30 min after this in all the patients of the "bleeding" group. These changes, involving the fibrinolytic system as well as a fall in concentration of all the coagulation factors, can probably be partly explained by the clamping and unclamping of mesenteric vessels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mechanisms and prediction of hemorrhagic complications during surgery of thoraco-abdominal aortic aneurysms]. 224 Jun 94

Bleeding complications during liver transplantation have been attributed to accelerated fibrinolysis. In order to determine its cause, 11 adults (mean age: 38.9 +/- 13.2 yr) undergoing liver transplantation were studied. There were three groups of patients: cirrhosis (n = 4), fulminating hepatitis (n = 4) and one group including a primary biliary cirrhosis, a hepatic metastasis and a hepatoma. The following factors were studied in the immediate preoperative period, at different surgical times throughout the procedure and 2-3 h after the end of the abdominal sutures: platelet count, prothrombin concentration, fibrinogen, activated kephalin time, factors II, V, VII + X and VIIIc, antithrombin III, protein C, D-dimers, fibrinogen and fibrin degradation products (PDF), plasma plasminogen, tissue plasminogen activator (tPA) and the fast tPA inhibitor (PAi). Preoperatively, only the two patients with hepatic cancer had a normal haemostatic profile. Throughout the procedure, all patients had only moderate changes in platelets, coagulation factors and their inhibitors, and plasminogen, because platelet concentrates and fresh frozen plasma were transfused. Levels of tPA rose, becoming very high during the anhepatic period and just after graft reperfusion. An abrupt fall occurred at the end of surgery. There were important individual differences in tPA activity. PAi activity was low during the preanhepatic and anhepatic stages, rising rapidly after revascularization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fibrinolytic activity in patients undergoing hepatic transplantation]. 249 27

Certain group A streptococci are known to possess a receptor for the human enzyme plasmin. Plasmin is a member of a super gene family that includes other serine proteases and kringle containing proteins. In this study we have examined the interaction of a group A streptococcus with structurally related proteins, including plasmin, glu-plasminogen, tissue plasminogen activator, kallikrein, factor XII, prothrombin, thrombin, trypsin, and urokinase. Our studies indicate that only the key fibrinolytic enzyme, plasmin, demonstrates significant binding activity to the group A streptococcus.
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PMID:Group A streptococci bind human plasmin but not other structurally related proteins. 255 Oct 62

A thorough screening procedure to diagnose congenital coagulation disorders must start from a careful collection of the personal and family clinical history, followed by a two-step laboratory screening. The first step is aimed at detecting the most frequent and well established causes of hemorrhage by a simple battery of laboratory tests such as bleeding time, platelet count, prothrombin time and activated partial thromboplastin time. The second step is to be performed in case of a past history of bleeding, but normal first-step laboratory screening and is aimed at detecting the less frequent abnormalities of hemostasis such as factor XIII, antiplasmin, platelet factor 3, von Willebrand factor, tissue plasminogen activator and dysfibrinogenemia, to which the first-step screening tests are not sensitive.
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PMID:Screening for congenital coagulation disorders. 263 99

There is uncertainty as to which preoperative examinations are necessary before performing regional anesthesia. Therefore an interdisciplinary consensus conference was established to obtain recommendations on some of the open questions related to this topic. Preoperative laboratory examinations are not necessary prior to peripheral nerve blocks near large vessels if these are easy to compress. In patients on anticoagulant therapy direct puncture of the vessel should be avoided. Prior to spinal or epidural anesthesia, no preoperative laboratory examinations are necessary if no anamnestic or clinical evidence of coagulation disorders exists. Otherwise the following examinations are useful: clotting time, prothrombin time, partial thromboplastin time (PTT), and thrombocyte count. Low-dose heparin prophylaxis is no contraindication to spinal or epidural anesthesia. However, in patients at increased risk of bleeding or with low body weight, PTT and thrombocyte count are necessary. Since at present no definite data exist as to the bleeding risk in patients treated with low-molecular-weight heparin prophylaxis, spinal/epidural anesthesia should be performed in controlled studies only under these conditions. This particular precaution seems to be necessary because low-molecular-weight heparin increases levels of plasminogen activators (t-PA) and therefore has fibrinolytic activity. If plasma expanders are administered perioperatively, the highest bleeding risk exists after dextran infusions. There is also an increased bleeding risk if nonsteroidal anti-inflammatory drugs, especially acetylsalicylic acid, are administered repeatedly within 5 days prior to spinal/epidural anesthesia. In these patients preoperative determination of the clotting time appears necessary.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hemostatic requirements for the performance of regional anesthesia. Workshop on hemostatic problems in regional anesthesia]. 268 21

In an open-study design five healthy volunteers were first given 2500 IU sodium heparin intravenously and then, after 72 h, another injection of the same dosage of sodium heparin followed immediately by 400 mg defibrotide intravenously. In two separate experiments, prothrombin time, activated partial prothrombin time, antithrombin III, tissue plasminogen activator, its inhibitor and plasma heparin levels were measured at baseline and after 15 min in one experiment, and at baseline and after 2 h in the other experiment. The most important finding was that an interaction exists between heparin and defibrotide on haemostatic activity: activated partial prothrombin time was increased three-fold in volunteers given the defibrotide--heparin combination compared with volunteers given heparin alone. This statistically and clinically significant effect was evident 15 min after administration of defibrotide--heparin and was still present after 2 h. Possible explanations for this effect are discussed briefly.
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PMID:Effects of a defibrotide-heparin combination on some measures of haemostasis in healthy volunteers. 270 75


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