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

A consumption coagulopathy syndrome has frequently been reported in association with some cases of acute nonlymphoblastic leukemia (ANLL) and mainly in acute promyelocytic leukemia (M3). Eighteen cases of ANLL have been studied on admission, before chemotherapy was started. Levels of antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (T-AT-III), tissue plasminogen activator, plasminogen (Pg), alpha-2-antiplasmin (alpha-2-AP), D-dimer (DD) and fibrinogen (Fg) were determined. The results showed normal levels of AT-III and PS, decreased levels of PC, alpha-2-AP, Pg and Fg in some cases, and an elevation of DD and T-AT III complex in almost all patients. There was a continuous evolution of data from M1 cases in which only slight alterations were seen up to M3 cases where all those pathologic data were observed.
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PMID:A continuous spectrum of hypercoagulability exists in acute nonlymphoblastic leukemia. 128 98

We observed the changes of molecular markers for hemostatic activation in a patient with acute pulmonary embolism treated with 2 x 10(7) unit tissue plasminogen activator (t-PA). Blood samples were obtained before, just after, at 30 min, 1, 2, 6, and 24 hours after the infusion. Molecular markers included thrombin-antithrombin III complex (TAT), plasminogen-alpha 2 plasmin inhibitor complex (PIC), and thrombomodulin (TM). Marked elevation of TAT was observed from immediately after the t-PA infusion to 6 hours after, although it had been observed for only 1 hour in our previous report on the cases of acute myocardial infarction. PIC level was significantly increased during t-PA infusion but returned to almost baseline value 6 hours after the end of t-PA infusion. This finding was almost the same as the one previously reported concerning acute myocardial infarction cases. TM level increased throughout the evaluation, and remained so, even on the 7th day after t-PA infusion. Our present data revealed a clear difference between the reactive TAT increases after t-PA therapy in acute myocardial infarction cases and in acute pulmonary embolism cases. Our present data also revealed a prolonged elevation of TM during the acute period of pulmonary embolism. It is therefore necessary to keep an eye on the changes of molecular markers for hemostatic activation after t-PA therapy in acute pulmonary embolism.
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PMID:[The changes in molecular markers for hemostatic activation after t-PA therapy in case of pulmonary embolism]. 131 73

Heparin is indispensable anticoagulant for cardiopulmonary bypass, but the dose of heparin is even now under discussion. In this study, hemostatic fluctuation was analyzed during and after the bypass using hemostatic molecular markers. The subjects were 16 adult cases of open heart surgery, 12 males, 4 females. The average age was 55.0 year. Operations were aortocoronary bypass in 12, valvular surgery in 3 and ASD patch closure in one with moderate hypothermic cardiopulmonary bypass. At the beginning of cardiopulmonary bypass, 3 mg/kg heparin was administered and the equivalent amount of protamine sulfate was used for neutralization at the end of the bypass. Platelet count, hematocrit, antithrombin III (ATIII), beta-thromboglobulin, platelet factor 4, fibrinopeptide A, thrombin antithrombin III complex, FDP, D dimer FDP, plasmin alpha 2 plasmin inhibitor complex, tissue plasminogen activator (t-PA), and thrombomodulin (TM) were measured through the operation up to two weeks after surgery. ATIII decreased to 50% of control value all through the bypass. Platelet markers increased immediately, and the activated state continued 3 hours after the bypass. Coagulation markers increased markedly after the aortic declamping, and reached at its peak by three times as control value, immediately after the protamine neutralization and continued for 3 hours. During the bypass, fibrinogenolysis caused by t-PA which was stimulated by non-physiological circulation and stimulating substances, was observed. Fibrinolysis occurred following the hypercoagulability after the neutralization. TM was within normal range before the aortic declamping. But increased gradually after the declamp, and reached twice as much as the base line. It could be concluded that hypercoagulability and high platelet activation might play a role of perioperative thrombosis. Hypercoagulability and increase of serum TM would be related to reperfusion of the lung. The increasing of TM would reflect broad injury of vessel walls after the bypass, because plasma TM increased following the generalized injury of endothelial cells.
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PMID:[A clinical study on hemostatic fluctuation during and after cardiopulmonary bypass using hemostatic molecular markers]. 133 89

We investigated heparin cofactor II (HC II) levels and their relationship to other haemostatic factors in the elderly in comparison with antithrombin III (AT III). We measured plasma HC II activity levels in 166 subjects aged from 61 to 99 years using a chromogenic method. HC II levels (94.4 +/- 18.5%) in the healthy elderly subjects were significantly (p less than 0.001) lower than in 40 healthy adult controls under 60 years of age (mean age: 51.5 years; 111.6 +/- 21.2%). HC II levels in the elderly subjects decreased further with age (r = 0.308, p less than 0.001) and the extent of the decrease was more marked than that for AT III (r = 0.179, p less than 0.05). There was no significant sex difference in HC II levels in the elderly. HC II levels correlated significantly with AT III levels and with acute phase reactants including sialic acid, fibrinogen, and PAI-1. HC II levels also correlated with factor VII, plasminogen, alpha 2-plasmin inhibitor, serum lipid, pseudocholinesterase, and albumin levels. These correlations were also found for AT III except active PAI-1 and tPA-PAI-1 complexes, but the correlations with acute phase reactants were stronger for HC II than AT III. We divided 154 elderly subjects into 4 groups by their pseudocholinesterase and albumin levels to estimate the effect of nutritional status on antithrombin activity in the elderly. HC II levels were normal in the elderly subjects with a good nutritional state (103 +/- 18%), but were significantly decreased in those with malnutrition (85 +/- 15%, p less than 0.001). AT III levels also showed the same tendency. These results indicate a decrease in the reserve capacity to inhibit thrombin generation at sites of atherosclerosis in response to trigger events. The deficiency of two major antithrombin factors in the elderly may indicate a tendency to thrombosis, especially in individuals with malnutrition. When considering the clinical significance of HC II, several other parameters, including age, nutritional status, hepatic synthetic ability, and the presence or absence of acute phase reaction should also be assessed.
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PMID:Heparin cofactor II deficiency in the elderly: comparison with antithrombin III. 138 49

Lipoprotein(a) (Lp(a)) has been established as an important independent risk factor for the development of cardiovascular disease. Apolipoprotein(a), together with apo B-100 the apolipoprotein of Lp(a), is homologeous to plasminogen but lacks fibrinolytic capacity and appeared to interfere with fibrinolysis in in vitro and ex vivo experiments. We determined the correlations between Lp(a) and other blood lipids (serum cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), coagulation parameters (fibrinogen, factor VII, factor VIII:C fibrin monomers, thrombin-antithrombin III) and fibrinolysis parameters (tissue plasminogen activator antigen, plasminogen activator inhibitor-1 and D-dimer) in 54 patients with essential hypertension, in 65 non-insulin-dependent diabetic patients and in 116 insulin-regulated diabetic patients. Signs of activated coagulation and increased reactive fibrinolysis were found in all three patient groups. In the hypertensive patients, Lp(a) was significantly correlated with LDL-cholesterol (r = 0.25, P = 0.04) and triglycerides (r = -0.30, P = 0.03), while in insulin-regulated diabetics, Lp(a) was also correlated with LDL-cholesterol (r = 0.20, P = 0.03). In the hypertensive patients and both diabetic groups there was no correlation of Lp(a) with coagulation or fibrinolysis parameters. These data show that Lp(a) concentrations are not related to coagulation or fibrinolysis parameters in hypertensive or diabetic patients and confirm the presence of an activated coagulation system in these patient groups.
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PMID:Low order correlations of lipoprotein(a) with other blood lipids and with coagulation and fibrinolysis parameters in hypertensive and diabetic patients. 138 33

Cardiopulmonary bypass during open-heart surgery is sometimes associated with excessive perioperative bleeding. Following a non-randomized study suggesting that desmopressin acetate (desmopressin) reduced blood product requirements in these patients, we conducted a double-blind, placebo-controlled randomized trial of desmopressin (0.3 micrograms/kg, i. v.) in 92 patients with overt bleeding and a prolonged bleeding time. Mean blood loss during the first 24 h post-treatment was similar in the desmopressin and placebo groups (582 vs 465 ml, respectively; p = 0.15). Red-cell (p = 0.76), fresh frozen plasma (r = 0.66) and platelet unit (p = 0.74) requirements were also similar. The haemostatic effect of desmopressin has been attributed to the release of von Willebrand factor (vWF) and a reduced bleeding time. In our study, vWF and factor VIII:C levels increased while the bleeding time decreased significantly at 90 min and 24 h in both groups and, although vWF and factor VIII:C levels were slightly higher in desmopressin-treated patients at 90 min, the difference was not significant. Thrombin-antithrombin III complex, fibrinogen degradation product and tissue plasminogen activator levels, reflecting activation of the coagulation and fibrinolytic systems, respectively, decreased uniformly in both groups. We conclude that desmopressin is not useful in reducing blood loss or blood product requirements in patients with excessive immediate postoperative bleeding.
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PMID:Desmopressin has no beneficial effect on excessive postoperative bleeding or blood product requirements associated with cardiopulmonary bypass. 141 52

Recent epidemiological studies have shown some beneficial health effects of the long chain (n-3) polyunsaturated fatty acids found in fatty fish. Although the results of these studies are often ambiguous and inconclusive, they have prompted many intervention trials to study the effects of n-3 fatty acids (FA) on the cardiovascular risk profile. However screening of the literature revealed that many of the beneficial effects of fish (oil) were obtained in intervention studies which had several serious shortcomings in their design. Therefore we started a placebo controlled randomised trial with increasing doses of n-3FA (respectively 0; 1.12; 2.24 and 3.37 g n-3 FA/day) and in order to have a maximum compliance this study was done in healthy monks. Fifty eight subjects took the fish oil capsules during 12 months and were thereafter followed for another 6 months. We couldn't detect any effect of n-3 FA supplementation on total cholesterol, HDL cholesterol, LDL cholesterol, apo A1, Lp(a), HbA1C, glucose, fibrinogen, factor VIII, antithrombin III, plasminogen activator inhibitor, tissue plasminogen activator and von Willebrand factor concentration, on bleeding time or on systolic or diastolic blood pressure. A pronounced significant dose dependent decrease of triglyceride levels was seen, while a slight but statistical significant decrease of apo B levels was observed in the highest fish oil dose. As the importance of triglycerides in the pathogenesis of atherosclerosis is still under discussion, the clinical relevance of these finding is not clear at the moment. It seems therefore improbable that the anti-atherosclerotic action of n-3 FA is due to an effect on the lipid, apoprotein, coagulation or fibrinolysis parameters as measured in our study. Hence further research must be focused on other parameters (prostaglandins) which can be influenced by n-3 FA and which probably play an equally important role in the atherosclerotic process.
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PMID:Influence of supplementation with N-3 fatty acids on different coronary risk factors in men--a placebo controlled study. 141 84

Plasma concentration of thrombin-antithrombin III complex (TAT), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), PAI-2, D-dimer complex and urokinase-plasminogen activator (u-PA) activity were studied in 30 patients with acute nonlymphoblastic leukemia (ANLL), before and during antileukemic therapy. Fifteen patients showed signs of disseminated intravascular coagulation (DIC), 10 of them classified as M3, 2 as M2 and 3 as M5 subtypes. The initial levels of TAT complex were elevated in all ANLL patients. This increase was more pronounced in patients with DIC (p less than 0.05). TAT increased significantly during the treatment period in all cases. u-PA and PAI-1 levels were elevated but there were no statistically significant differences between patients with and without DIC. PAI-2 levels were below the limit of detection in controls and in patients. However, the initially elevated D-dimer complex levels were significantly higher in DIC cases (p less than 0.01) and they increased during the treatment period. A significant and positive correlation between D-dimer and TAT complex values was found in DIC patients (r = 0.68, p less than 0.001). The high TAT complex and D-dimer levels further increased during chemotherapy treatment strongly suggest a hypercoagulable state with secondary activation of fibrinolysis not severe enough to manifest itself as clinically evident DIC in the majority of cases.
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PMID:Increase in the D-dimer levels during treatment in patients with acute myelogenous leukemia. 142 55

Effects of anticoagulant or fibrinolytic therapy on anterior chamber fibrin following cataract surgery was evaluated. In one series of experiment, various amounts of antithrombin III (ATIII), an anticoagulant, were injected into the anterior chamber of the rabbit eye immediately after phacoemulsification of the lens. In another series, various amounts of tissue plasminogen activator (TPA), a fibrinolytic agent, were injected into the anterior chamber 24 hours after phacoemulsification when it was filled with fibrin. The extent of the fibrin clot was graded using a slit lamp microscope, and the aqueous flare intensity was determined with a laser cell-flare meter for 2 weeks after operation. The eyes treated with TPA was also examined with light and electron microscopy. ATIII showed an inhibitory effect on fibrin formation, but complete inhibition was not obtained even with the highest concentration used. In contrast, the fibrin clot was completely resolved even with the lowest dose of TPA used, while no side effect such as inflammation or bleeding was seen. Histological examinations revealed no pathological changes in eyes treated with TPA. TPA may be a promising agent for fibrin resolution after cataract surgery.
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PMID:[Anticoagulant and fibrinolytic therapies for anterior chamber fibrin following cataract surgery in the rabbit eye]. 144 47

Semen specimens from four groups of patients were evaluated for coagulation and fibrinolysis factors: a group of patients with infertile semen and involuntary childlessness (n = 35), a group with fertile semen and involuntary childlessness (n = 39), a group with fertile semen and proven fertility before vasectomy (n = 34) and a group with infertile semen after vasectomy (n = 147). The third patient group with proven fertility before vasectomy was considered as a control group. Only small amounts of fibrinogen, factor VIII:c, plasminogen, antithrombin III, fibrin monomers and plasminogen activator inhibitor-1 were detected in seminal plasma. The thrombin-antithrombin III, D-dimer and tissue plasminogen activator regular concentrations were measured and the D-dimer/thrombin-antithrombin III ratios calculated. The reference ranges were assessed and the quantities were compared in the different patient groups. Significant differences were demonstrated between the prevasectomy group (= control group) and both the postvasectomy and the infertility groups with respect to D-dimer and D-dimer/thrombin-antithrombin III ratio. We conclude that both coagulation and fibrinolysis play a part in coagulum formation and liquefaction of seminal plasma. The balance between coagulation and fibrinolysis (expressed as D-dimer/thrombin-antithrombin III ratio) was significantly different between the control group and the three patient groups. The coagulation/fibrinolysis balance was impaired in the semen from post vasectomy patients and from those with involuntary childlessness and the D-dimer/thrombin-antithrombin III ratios in both these patient groups were very similar.
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PMID:Coagulation and fibrinolysis markers in seminal plasma of patients under evaluation for involuntary childlessness. 144 60


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