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)

Diabetes mellitus (DM) is associated with an increased incidence of vascular complications. Abnormalities in the hemostatic system contribute at least in part to the development of vascular disease or atherosclerosis. In order to assess the actual degree of activation of the coagulation and fibrinolytic systems in diabetics, plasma levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2-plasmin inhibitor complex (PAP) were measured together with tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) in 18 patients with DM (three patients with type I DM and 15 with type II DM). Mean plasma levels of TAT (2.5 +/- SD 1.2 ng/mL) and PAP (0.9 +/- 1.2 micrograms/mL) were significantly elevated in diabetics as compared with healthy subjects (1.7 +/- 0.3 ng TAT and 0.2 +/- 0.1 micrograms PAP per mL of plasma; p = 0.009 and 0.02, respectively). Plasma antigen concentration of t-PA but not of PAI-1 was also elevated. No difference was found in the levels of these variables between type I and type II diabetics or between patients with and without retinopathy or nephropathy. These findings indicate that continuous activation of coagulation and fibrinolysis actually occurs in the majority of the patients with DM.
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PMID:Activation of blood coagulation and fibrinolysis in diabetes mellitus: evaluation by plasma levels of thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex. 238 33

The effect of heparin as an anticoagulant was examined and the extent of fibrinolytic activity during cardiopulmonary bypass (CPB) was measured. Twenty patients undergoing valve replacement or aortocoronary bypass surgery were studied. Fibrinopeptide A (FPA) levels gradually became elevated as CPB proceeded, and antithrombin III (AT III) decreased during CPB. This indicates that despite the use of heparin, the coagulation system was activated, leading to fibrin formation in the microcirculation. On the other hand, fibrinopeptide B (FPB beta 15-42) also increased to four times the preoperative value at two hours on CPB. Intrinsic fibrinolytic activity, as determined by the activity of kaolin-activated euglobulin, was transiently increased only at the beginning of CPB. The C1 inactivator-resistant fibrinolytic activity and tissue plasminogen activator antigen (t-PA;Ag) increased sharply during CPB and reached maximum levels one hour after the start of CPB, indicating that enhanced fibrinolytic activity during CPB is predominantly of extrinsic origin as the result of t-PA release from the vascular walls. It is concluded from the above findings that thrombin activity continues during CPB. Enhanced fibrinolytic activity during CPB appears to be important because t-PA activates plasminogen predominantly where fibrin is formed, leading to dissolution of the microthrombi formed during CPB.
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PMID:Alterations in coagulation and fibrinolysis associated with cardiopulmonary bypass during open heart surgery. 253 75

Changes in the protein C-thrombomodulin (PC-TM) system in relation to other coagulofibrinolytic parameters were examined in 25 patients undergoing open heart surgery. Although all patients were given heparin, a decrease in antithrombin III (ATIII) and progressive increase in thrombin-ATIII complex (TAT) and fibrinopeptide A (FPA) levels were noted during cardiopulmonary bypass, which indicated that heparinization did not completely inhibit the formation of thrombin and its function. C1-inactivator (INA) resistant fibrinolytic activity increased markedly during CPB, in parallel with the change of tissue plasminogen activator antigen (t-PA;Ag), which indicates that fibrinolytic activity during CPB is mainly of extrinsic origin caused by t-PA. Protein C antigen (PC;Ag), protein S antigen (PS;Ag), and thrombomodulin antigen (TM;Ag) were all decreased significantly during CPB. This is considered to reflect the activation and consumption of the PC-TM system in response to generated thrombin. Furthermore, enhancement of the extrinsic fibrinolytic system is easily explained by the action of activated PC, which counteracts plasminogen activator inhibitor (PAI-1), to cause enhancement of t-PA activity.
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PMID:The role of the protein C-thrombomodulin system in physiologic anticoagulation during cardiopulmonary bypass. 255 68

An increase in plasma fibrinogen content and a decrease in level of antithrombin III in plasma with ageing may cause a thrombotic tendency in the elderly, although the main cause of thrombosis in the aged is atherosclerotic change seen in these subjects. Coagulability of blood is maintained in the so-called therapeutic range in aged patients receiving oral anticoagulant, as well as in younger subjects, however, it has been pointed out that there is an increasing risk of hemorrhage, especially of intracranial hemorrhage, with advancing age. Intracranial hemorrhage is not necessarily a rare complication of anti-platelet or thrombolytic therapy in the aged. Another hazard of aspirin therapy in the aged is the abrupt development of peptic ulcer. The authors administered 40 mg of aspirin per day to ten volunteers. In these subjects, platelets in the venous blood taken in a glass tube were strongly stimulated by coagulating whole blood in the tube for 60 minutes at 37 degrees C. Under this condition, arachidonic acid in platelets was converted to thromboxane B2, which is a stable metabolite of thromboxane A2 that causes platelet aggregation and vasoconstriction to accelerate thrombus formation. After ingestion of the minidose aspirin for one week, the concentration of thromboxane B2 in the serum (not in the plasma) of the volunteers decreased to 7% of the values determined before the administration of the drug, because of inhibition of cyclo-oxygenase in the platelets by aspirin. However, concentration of 6-keto-PGF1 alpha, which is a stable metabolite of prostacyclin that originates from arachidonic acid by cyclo-oxygenase in the vessel wall, did not markedly decrease after the treatment with aspi2+ t-PA and hybrid of t-PA and scu-PA in the aged are discussed. If antithrombotic therapy is always safe in the aged, it may be rational and economical to select subjects predisposed to thrombosis among patients with atherosclerosis. Determination of levels of fibrinogen, beta-thromboglobulin and/or thrombin-antithrombin III complex in plasma may be useful to predict thrombosis.
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PMID:[Antithrombotic drugs]. 267 54

Eighty patients undergoing total hip replacement (THR) were randomly allocated to three groups. Group I (n = 29) received general anaesthesia, Group II (n = 29) epidural anaesthesia and Group III (n = 22) the same epidural as Group II and the same general anaesthesia as Group I but with a lower isoflurane concentration. Prothrombin time (PT), activated thromboplastin time (APTT), fibrinogen (FG), plasminogen (PG), antithrombin III (AT III), protein C (Proc C), alpha-2-antiplasmin (alpha 2AP), Factor VIII coagulating activity (F VIII:C), von Willebrand factor antigen (vWF:Ag), von Willebrand ristocetin cofactor (vWF:Rcof), tissue plasminogen activator (tPA) as antigen and activity were measured before induction (A), at the end of surgery (B), on the first postoperative morning (C) and 7 days postoperatively (D). The most relevant finding was that AT III was equally depressed immediately after surgery in all groups, but returned to normal significantly faster in the epidural group (mean values at C: 96.2% in Group I, 104.1% in Group II, 92.7% in Group III). The faster return to normal of AT III after epidural anaesthesia could be one of the mechanisms responsible for the beneficial effect of this technique on the prevention of thromboembolic complications.
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PMID:Coagulation and fibrinolytic parameters in patients undergoing total hip replacement: influence of the anaesthesia technique. 268 46

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

Fibrin II monomer has a dramatic inhibitory effect on the rate of heparin-catalyzed inactivation of human alpha-thrombin by antithrombin III. At 6 microM fibrin II monomer, equivalent to the concentration of fibrinogen in plasma, the second-order rate constant was reduced by a factor of 308--from 2.05 x 10(8) M-1.s-1 to 6.65 x 10(5) M-1.s-1. Fibrin II monomer minimally affected the uncatalyzed rate of thrombin inactivation showing a reduction in the second-order rate constant by a factor of only 1.6. Fibrinogen and the product of plasmin degradation of fibrinogen, fragment E, at 6 microM concentrations also decreased the second-order rate constant for heparin-catalyzed thrombin inactivation, but by factors of only 2.7 and 1.9, respectively. On the basis of these observations it is proposed that protection of thrombin from inactivation by heparin-antithrombin III by fibrin II monomer can explain the limited efficacy of heparin in preventing coronary reocclusion in patients treated with tissue plasminogen activator and other fibrinolytic agents.
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PMID:Fibrin monomer protects thrombin from inactivation by heparin-antithrombin III: implications for heparin efficacy. 272 39

Inflammatory bowel disease (IBD) is known to be associated with a thrombotic tendency, which is often attributed to thrombocytosis, elevated fibrinogen, or decreased antithrombin III. We prospectively studied eight patients with IBD, seven of whom had little or no disease activity, to determine if they had any laboratory abnormality known to be associated with an increased risk of thrombosis. Abnormalities in fibrinolysis were noted in five patients: four with high plasminogen activator inhibitor levels and one with poor release of tissue plasminogen activator following venous occlusion. Circulating immune complexes were present in the sera of five patients. Fibrinogen was mildly elevated in one patient, and two patients had mild thrombocytosis. Decreased levels of antithrombin III, protein C, or protein S were not observed. There appears to be a high incidence of abnormalities in fibrinolysis in inactive IBD, which may contribute to the high frequency of thrombosis seen in IBD. The presence of circulating immune complexes may contribute to vascular injury and thrombosis.
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PMID:Prothrombotic abnormalities in inflammatory bowel disease. 274 49

Hemostatic changes were evaluated in ten patients with acute lymphoblastic leukemia and lymphoma who received chemotherapy with L-asparaginase, vincristine, and prednisolone for 1 week. Following treatment, prothrombin time and activated partial thromboplastin time were significantly prolonged, while a marked decrease in fibrinogen levels was observed. The values for cross-linked fibrin degradation products, however, remained within normal limits during treatment, which excluded the possibility of disseminated intravascular coagulation. The concentrations of coagulation inhibitors (antithrombin III, protein C, and protein S), plasminogen, and alpha 2 antiplasmin also significantly decreased; however, levels of both tissue-type plasminogen activator and plasminogen activator inhibitor, which are synthesized in endothelial cells, increased during the treatment. Although a decrease was observed in concentrations of many coagulation factors, including subunits A and B of factor XIII, the activity and antigenicity of factor VII significantly increased following the treatment. From this study, we concluded that these hemostatic abnormalities caused by the administration of L-asparaginase produced a labile condition that easily inclines to bleeding or thrombosis.
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PMID:Changes in hemostatic and fibrinolytic proteins in patients receiving L-asparaginase therapy. 275

Fetal and neonatal lamb hemostasis were studied from the 60th day of pregnancy to birth. Platelet counts and blood coagulation, as assessed by tests such as recalcification time and thromboelastography, were similar in fetuses, neonates, and adult sheep. The values of coagulation factors were low, ie, vitamin K-dependent Factors II, VII, IX, and X remained unchanged (30 and 40% of adult reference values) until the last 10 days of gestation, and then increased until birth (40 to 60%). Values of fibrinogen and Factor V followed a similar pattern, although their activities became identical to adult values at birth. Also, we measured values of protein C and antithrombin III, which are synthesized by the liver. The importance of hepatic failure and fetal vitamin K deficiency were discussed. Factors VIII and XII activities increased gradually during pregnancy to reach adult values at birth. Fetal fibrinolytic activity increased. This could not be explained by the values of tissue-type plasminogen activator (it was not detectable) or by the presence of its fast-acting inhibitor, whose concentration did not decrease.
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PMID:Hemostasis development in the lamb fetus and neonate. 291 28


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