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)

Desmopressin (DDAVP) 0.3 micrograms/kg was administered intravenously to three normal volunteers and 12 patients with von Willebrand's disease (vWD), congenital or acquired platelet function defect, or uremic bleeding to assess its effects and side effects. DDAVP significantly shortened the bleeding time as compared with basal values. The mean peak post-DDAVP level of factor VIII coagulant activity increased 5.9 +/- 0.5 (mean +/- SEM) fold, von Willebrand factor antigen increased 3.7 +/- 0.3 fold, von Willebrand factor ristocetin cofactor activity increased 4.6 +/- 0.6 fold and the tissue-type plasminogen activator antigen increased 3.4 +/- 0.6 fold. Analysis of the multimeric structure of the von Willebrand factor revealed that type I vWD had complete correction after DDAVP infusion transiently. Except for a mild drop in both systolic and diastolic blood pressures, few side effects were noted. By concomitant intravenous infusion of DDAVP and oral administration of tranexamic acid, we successfully treated two cases of type I vWD undergoing tooth extraction, and one case of acquired bleeding disorder undergoing a biopsy of a mandibular mass, and a uremic patient complicated by intractable traumatic hematuria. Our experiences confirmed that most patients with vWD and some patients with congenital or acquired bleeding disorders can be treated effectively by DDAVP infusion without the need for plasma product replacement. In this study we found that a patient with a variant form of type I vWD had prolongation of the bleeding time, thrombocytopenia and platelet aggregation after DDAVP infusion.
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PMID:Experience of desmopressin (DDAVP) administration in patients with congenital and acquired bleeding disorders. 136 75

When patients with mild haemophilia or von Willebrand disease (vWD) are repeatedly treated with desmopressin (DDAVP) at relatively short time intervals, some of them may become less responsive or unresponsive. The development of tachyphylaxis would limit the usefulness of DDAVP in clinical management of these patients. On the other hand, tachyphylaxis is not consistent, and its patterns of development are unknown. The aim of this study was to evaluate in controlled conditions the occurrence of tachyphylaxis by giving intravenous DDAVP (0.3 microgram/kg) on four consecutive days to a selected group of patients with mild haemophilia A (n = 22) and type I vWD (n = 15). After each dose, we measured parameters known to change after DDAVP, i.e. factor VIII coagulant activity, bleeding time, von Willebrand factor antigen, ristocetin cofactor and tissue-type plasminogen activator antigen. We found that on average the responses obtained after the second dose of DDAVP were approximately 30% less than those obtained after the first, but were not further reduced after the third and fourth dose. At all time intervals after DDAVP, patients with vWD responded relatively better than patients with haemophilia, and there were fewer vWD patients who responded poorly or became unresponsive. In vWD patients there were no significant changes in the bleeding time responses and in blood pressure and heart rate. The clinical implications of these findings are that repeated doses of DDAVP can be given efficaciously to many patients (particularly to those with vWD), even though responses lower than those seen after the first dose should be expected.
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PMID:Patterns of development of tachyphylaxis in patients with haemophilia and von Willebrand disease after repeated doses of desmopressin (DDAVP). 141 7

Plasma levels of tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) antigen and t-PA/PAI-1 complex were measured in plasmas from 18 healthy subjects and 75 patients with various diseases (28 patients with haematological malignancies, 20 with thrombotic diseases, five with infectious diseases, four with liver diseases, ten with bleeding disorders and eight miscellaneous conditions). In addition, we studied ten patients with bleeding disorders after DDAVP infusion and 18 healthy subjects after venous occlusion. Plasma levels of t-PA antigen, PAI-1 antigen and t-PA/PAI-1 complex were increased in the patients compared with the healthy subjects. t-PA/PAI-1 complex levels correlated well with t-PA antigen levels and molar concentrations of t-PA antigen were similar to those of the t-PA/PAI-1 complex. Venous occlusion induced an increase in both t-PA antigen and PAI-1 antigen and the molar concentration of the t-PA/PAI-1 complex was equivalent to that of t-PA antigen. Following DDAVP infusion, the levels of t-PA antigen and t-PA/PAI-1 complex increased but PAI-1 antigen levels decreased, and the increase of t-PA antigen was greater than that of t-PA/PAI-1 complex. These findings indicate that PAI-1 antigen exceeds t-PA antigen in healthy subjects and in patients with various diseases. We conclude that part of the t-PA/PAI-1 complex is rapidly cleared from the circulation and that free t-PA increases after DDAVP infusion.
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PMID:Behaviour of tissue plasminogen activator, plasminogen activator inhibitor 1 and their complex in various disease states. 142 Aug 14

The contribution of activation of the contact system to activation of the fibrinolytic system in vivo was investigated in healthy volunteers and in factor XII deficient patients. The plasminogen activating activity in normal plasma was only partially blocked (for 77%) with specific antibodies to tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). The residual activity could be quenched by a monoclonal antibody that inhibits factor XII activity and was not present in patients with a factor XII deficiency. The formation of plasmin upon the DDAVP stimulus as reflected by circulating plasmin-alpha 2-antiplasmin (PAP) complexes was lower in factor XII deficient patients than in healthy volunteers. These results indicate that in vivo the plasminogen activating activity is partially dependent on activation of the contact system. This fibrinolytic activity is impaired in factor XII deficient patients which may explain the occurrence of thromboembolic complications in these patients.
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PMID:Contact system dependent fibrinolytic activity in vivo: observations in healthy subjects and factor XII deficient patients. 146 34

Nine healthy volunteers and 23 patients with various types of von Willebrand disease were studied before and after DDAVP infusion. We investigated the behaviour of factor VIII/von Willebrand factor measurements, and of tissue plasminogen activator and urokinase-type plasminogen activator. In mild von Willebrand disease the increase of both plasminogen activators was similar to that seen in normal controls. A different fibrinolytic behaviour was found in the type I platelet low and in the type III von Willebrand disease patients. An impaired and absent fibrinolytic response to DDAVP was seen in the former and in the latter von Willebrand disease, respectively. A close relation between either u-PA and t-PA or von Willebrand factor was observed. The possibility of a linkage among these three proteins was discussed.
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PMID:Urokinase-type plasminogen activator release after DDAVP in von Willebrand disease: different behaviour of plasminogen activators according to the synthesis of von Willebrand factor. 152 8

In the present study 57 consecutive patients with a first episode of venographically proven deep vein thrombosis were investigated to evaluate the release of tissue-type plasminogen activator (t-PA) and of urokinase-type plasminogen activator (u-PA) in response to DDAVP stimulation as well as the resting plasminogen activator inhibitor (PAI) concentration, comparing this to the results obtained in 66 similar patients with a clinical suspicion of thrombosis but with a normal venogram. All assays were performed without knowledge of the patient's status. Four patients in the deep vein thrombosis-group (7%) had an absent u-PA antigen response upon DDAVP infusion, while a normal response was observed in all control subjects. Patients and controls showed similar increases in t-PA antigen level upon DDAVP. High resting PAI antigen levels were encountered in 5 patients in the deep vein thrombosis-group (9%) and in 6 subjects in the control group (9%). The results from this controlled study indicate that a defective release of u-PA may occur in patients with deep vein thrombosis and may have pathogenetic significance. Furthermore it is concluded that elevation of PAI levels cannot be considered as a specific risk factor for venous thrombosis.
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PMID:Deep vein thrombosis and fibrinolysis. Defective urokinase type plasminogen activator release. 179 91

Twelve patients undergoing total hip replacement, with regional anaesthesia and with dextran infusion for plasma expansion and thromboprophylaxis, were given the vasopressin analogue desmopressin (DDAVP) or placebo in a randomized, double-blind prospective study. In controls (n = 6) we found a prolongation of the bleeding time, low factor VIII (FVIII) and von Willebrand factor (vWF) and a decrease in antithrombin III to levels known to be at risk for venous thrombosis. Desmopressin shortened postoperative bleeding time, gave an early FVIII/vWF complex increase, prevented antithrombin III from falling to critically low values and appeared to activate the fibrinolytic system, both by tPA increase and PAI-1 decrease. Thus in the controls we found changes in both coagulation and fibrinolysis indicating a haemorrhagic diathesis as well as a risk for thromboembolism. Desmopressin induced factor changes that possibly reduce both risks.
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PMID:Effects on coagulation and fibrinolysis of desmopressin in patients undergoing total hip replacement. 179 9

Desmopressin acetate (DDAVP) is known to stimulate the release of tissue-type plasminogen activator (t-PA) from endothelial cells, but it is unclear whether the increased t-PA actually elicits the plasmin generation and fibrin(ogen)olysis in the circulating blood. We measured plasma levels of plasmin-alpha 2-plasmin inhibitor complex, fibrinogen degradation products (FgDP) and fibrin degradation products (FbDP) following desmopressin infusion in 19 patients with bleeding disorders or thrombophilia. Administration of desmopressin (0.3-0.4 microgram/kg) produced a 4.0-fold increase in plasmin-alpha 2-plasmin inhibitor complex at 30 min, whereas neither FgDP nor FbDP was elevated significantly. These findings indicate that desmopressin infusion provokes the generation of plasmin in vivo, but most of the plasmin generated is complexed to alpha 2-plasmin inhibitor and does not degradate fibrin or fibrinogen.
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PMID:Plasmin generation and fibrin(ogen)olysis following desmopressin infusion. 182 8

A 20-min venous occlusion and a desmopressin acetate (DDAVP, 0.4 microgram.Kg-1, 15 min) infusion test have been compared to evaluate fibrinolytic capacity in proven coronary artery disease. Basal values of plasma tissue plasminogen activator (t-PA) activity and antigen and of t-PA inhibitor (PAI) were normally distributed in this patient group. However, after both stimuli, highly significant (P less than 0.005) increases of t-PA antigen and activity have been observed. Renormalization of t-PA levels after DDAVP infusion occurred more rapidly for antigen (120 min) than for activity concentrations (greater than 240 min). A DDAVP infusion test seems more appropriate for evaluation of the fibrinolytic capacity as the induced decrease in PAI level was significant (P less than 0.005) and lasted for at least 240 min, while it was not significant for the venous occlusion test.
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PMID:Comparison of the fibrinolytic response to desmopressin acetate (DDAVP) infusion versus venous occlusion in patients with coronary artery disease. 190 28

Thrombotic events are often due to fibrinolytic defects such as impaired tissue plasminogen activator (tPA) synthesis and/or release or increased plasminogen activator inhibitor (PAI) levels. In this report we describe four members of a family with a history of recurrent venous thrombosis, who demonstrated defective tPA release after dynamic tests. Two symptomatic patients and one asymptomatic individual showed absent or abnormally low tPA antigen (tPA:Ag) and activity (PA) increases after DDAVP infusion and/or 20 min of venous occlusion. In these patients PAI values were slightly higher than controls. A satisfactory tPA:Ag release was found in the fourth asymptomatic patient. All other coagulation tests were within the normal ranges. This familial defect of the fibrinolytic system seems to be inherited as an autosomal trait.
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PMID:Venous thrombosis and tissue plasminogen activator release deficiency: a family study. 190 2


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