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)

The t-PA/PAI-1 complex is a good indicator of the release of fibrinolysis activators and inhibitors from the vascular wall, but its clinical significance in chronic ischemic heart disease is unclear. The plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and the t-PA/PAI-1 complex (including various coagulation factors) were assayed in 72 patients with coronary artery disease (CAD) and 29 control (C) subjects. The CAD patients were subdivided into 3 groups: single-vessel disease (G1, n = 30), double-vessel disease (G2, n = 20), and triple-vessel disease (G3, n = 22). The patients with triple-vessel disease had higher fibrinogen values (G3: 318 +/- 75 mg/dl, C: 263 +/- 56), factor VII activity (G3: 143 +/- 36%, C: 123 +/- 14), and t-PA antigen levels (G3: 4.7 +/- 0.8 ng/ml, C: 3.3 +/- 0.7) than controls. Patients with double- and triple-vessel disease also showed higher levels of factor VIII, vWF antigen, thrombin-antithrombin III complex (G1: 2.3 +/- 0.6 ng/ml, G2: 2.7 +/- 0.5, G3: 3.1 +/- 0.5, C: 2.0 +/- 0.5), and t-PA/PAI-1 complex (G1: 13.9 +/- 6.1 ng/ml, G2: 16.4 +/- 4.6, G3: 18.2 +/- 5.9, C: 10.7 +/- 4.9) than control subjects. The t-PA/PAI-1 complex levels were correlated significantly with the activities of factors VII and VIII and the thrombin-antithrombin III complex. These findings suggest that patients with CAD have greater blood coagulability than controls, and that this difference is related to the severity of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma t-PA/PAI-1 complex and blood coagulability in patients with coronary artery disease. 152 91

16 coagulant and 7 fibrinolytic parameters were determined in 121 normal subjects and 456 patients with various types of viral hepatitis. The results showed that plasma concentration of F VIII: c, vWF: Ag and vWF: Ag/VIII: c (P less than 0.01) were much higher than those in the controls. Plasma level of other coagulant factors was progressively reduced when the severity of hepatitis was decreased. The changes of fibrinolytic activity suggest that t-PA, PL and FDP were increased, while PAI, PLG, and alpha-PI were decreased. The results of this study may provide an experimental basis for further study of hemorrhage mechanism and prognosis in patients with viral hepatitis.
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PMID:[Changes in plasma coagulant factors and plasma fibrinolytic activity in patients with viral hepatitis]. 166 71

The effects of desmopressin and dextran on haemostasis and fibrinolysis were studied in four healthy volunteers. Both drugs were compared to placebo, each volunteer being subject to four experiments. Dextran 70 (30 g i.v.) moderately decreased VIII:C and vWF:Ag and slightly increased antithrombin III, also when haemodilution and diurnal variation were considered. Desmopressin (0.3 micrograms/kg BW i.v.), alone as well as in combination with dextran, increased VIII: C, vWF:Ag, protein C and tPA and decreased PAI-1. The combination of desmopressin and dextran stimulated coagulation and fibrinolysis and might be of relevance to surgical blood loss as well as to postoperative thromboembolism.
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PMID:Effects of desmopressin and dextran on coagulation and fibrinolysis in healthy volunteers. 171 90

The fibrinolytic response to venous occlusion was studied in 17 patients with inflammatory bowel disease: 7 with Crohn's disease, 10 with ulcerative colitis and compared with those obtained in 20 controls. Patients with inflammatory bowel disease showed decreased tissue-type plasminogen activator antigen release (t-PA Ag), no significant Von Willebrand antigen release (vWF Ag), and a residual plasminogen activator inhibitor activity (PAI activity) after venous occlusion. These modifications were more important in the evolutive colitis group compared with the remission group. Hypofibrinolysis, as defined by a defective t-PA release, and a residual PAI activity after venous occlusion might contribute to digestive and/or extra digestive thrombotic manifestations observed during the course of inflammatory bowel diseases.
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PMID:[Impaired fibrinolytic response to the venous occlusion test in patients with cryptogenic colitis]. 178 49

The plasma levels of several haemostatic and fibrinolytic parameters were measured before and after delivery in 61 hypertensive pregnant women of whom 22 developed preeclampsia, and compared to the results obtained in 42 normal pregnant women. In the two last weeks before delivery (D less than or equal to -15) tPA antigen, PAI-1 activity, vWF:Ag/FVIII:C ratio, ATIII activity and platelet count were found to be significantly different in the hypertensive pregnant women with and without preeclampsia. Combined all together, an association of three of these five parameters were found to be pathological (i.e.:tPA:Ag greater than or equal to 19 ng/ml, PAI-1 activity greater than or equal to 58 IU/ml, vWF:Ag/FVIII:C ratio greater than or equal to 2.6, ATIII activity less than or equal to 73%) in none of the hypertensive women without preeclampsia and in only 35% of the preeclamptic group. A positive correlation was demonstrated between vWF:Ag/FVIII:C ratio and tPA:antigen levels suggesting that both tPA and vWF:Ag could be considered as early indicators of a possible micro angiopathy occurring in preeclampsia. However, due to the high dispersion of the results, it appears that the investigated haemostatic and/or fibrinolytic criteria give only presumptive arguments before assigning risk for preeclampsia development among hypertensive pregnant women.
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PMID:Are haemostatic and fibrinolytic parameters predictors of preeclampsia in pregnancy-associated hypertension? 179 89

Various thrombosis related parameters of the hemostatic system were evaluated in 11 patients who had had bone marrow transplantation (BMT). At 0, 1, 3 and 6 months after BMT, antithrombin III, heparin cofactor II, protein S (PS), factor VIII:C, von Willebrand factor (vWF:Ag, vWF:RiCof), tissue plasminogen activator (tPA), plasminogen activator inhibitor, thrombin antithrombin III complexes (TAT), d-dimers (DD) and antiphospholipid antibodies (APA) were determined. A statistically significant rise in the levels of vWF was observed after BMT, with a similar trend for tPA. High TAT and/or DD were detected in 10/11 patients and positive APA only in 5/11. Of the other parameters only free PS was permanently low, with normal total PS and C4bBP. These findings suggest persistent thrombin generation peri- and post-BMT. The significantly high vWF and the low free PS could foster a procoagulant state.
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PMID:[Tendency to thrombosis following bone marrow transplantation?]. 190 84

There is a circadian variation in the time of onset of thrombotic disorders. The thrombotic tendency of blood is influenced by many factors including complex interactions between endothelial cells, platelets and red blood cells. We studied the circadian variation of various indices of these cells' functions in 10 young healthy male volunteers. Six blood samples were collected at 4 h intervals from 12.00 until 08.00 the following morning. The volunteers carried out normal daily activities until 00.00 at which time they went to bed. They remained in bed until 08.00 the following morning. The following were measured on each sample: plasma factor VIII von Willebrand factor antigen (FVIII vWF Ag), tissue plasminogen activator activity (tPA), plasminogen activator inhibitor (PAI), prostacyclin stimulating factor (PGI2 SF), fibrinopeptide A (FPA), 11 dehydro-thromboxane B2 (11-dehydro-TXB2) and red cell deformability (RCD). The following parameters demonstrated significant circadian variation: tPA P less than 0.001, PAI P less than 0.04 and 11-dehydro-TXB2 P less than 0.005 (two-way analysis of variance). tPA was highest at 16.00-20.00 and lowest at 08.00; PAI was highest at 08.00 and lowest at 20.00; TXB2 had a peak at 16.00 and trough at 04.00. As the behaviour of endothelial cells and platelets influence the rheological properties of blood, circadian variations in their behaviour may contribute to the time of onset of thrombotic disorders.
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PMID:Circadian variation of endothelial cell function, red blood cell deformability and dehydro-thromboxane B2 in healthy volunteers. 193 30

One hundred patients with a history of thrombophilia were divided into two groups based on fibrinolytic response to venous occlusion. Good responders with a euglobulin clot lysis time less than or equal to 105 min showed significant release of tPA, PAI and vWF. Of the poor responders with an ECLT greater than 105 min, 24% showed a subnormal increase in tPA, and a significant proportion of these also showed a reduced or absent rise in vWF. We have shown poor fibrinolytic response was related to either raised levels of PAI, poor release of both tPA and vWF, or poor release of tPA or vWF alone suggesting different mechanisms of fibrinolytic impairment. Protein S levels were not significantly changed in either group following occlusion.
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PMID:Changes in endothelial-related coagulation proteins in response to venous occlusion. 164 31

The venous occlusion test was applied to 17 patients with inflammatory bowel disease (IBD; 7 cases of Crohn's disease, 10 cases of ulcerative colitis). Results were compared to those obtained in 20 healthy matched control subjects. Patients with IBD had significantly decreased t-PA Ag release (p less than 0.001) and had no significant vWF Ag release. Residual PAI activity was evidenced after venous stasis in the IBD group but not in the control group. Hypofibrinolysis was more important in patients with an evolutive IBD than in patients with IBD in remission. Impaired systemic fibrinolytic capacity might contribute to an increased risk for thromboembolic complications and to the pathogenesis of inflammatory bowel disease.
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PMID:Impaired fibrinolytic capacity in patients with inflammatory bowel disease. 211 29

Three patients with congenital, nephrogenic diabetes insipidus (NDI) from two unrelated families were tested for haemostatic and fibrinolytic responses to DDAVP infusion and venous occlusion. None of the three patients showed a response of factor VIII:C, vWF:Ag or t-PA to DDAVP, a V2-agonist. However, the baseline levels of these factors in the patients' plasma were normal and during venous occlusion a rise in t-PA antigen and t-PA activity was observed in all patients. One patient showed a definite response of the t-PA antigen level to exercise. It is concluded that (extrarenal) V2-receptor-mediated responses are absent in these patients, but that baseline homeostasis and the response to venous occlusion and physical exertion are intact. Presumably, these depend on other mechanisms. This observation denies a central role for vasopressin receptors in the on-demand regulation of clotting and clot dissolving properties of the blood.
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PMID:Normal homeostasis of fibrinolysis in nephrogenic diabetes insipidus in spite of defective V2- receptor-mediated responses of tissue plasminogen activator release. 213 55


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