Tissue Plasminogen Activator as an Antiangiogenic Agent in Experimental Corneal Neovascularization in Rabbits

Background: We evaluated the diagnostic efficacy of tissue plasminogen activator (tPA), using an enzyme-linked immunosorbent assay (ELISA) and compared it with an ELISA D-dimer (VIDAS D-dimer) in acute pulmonary embolism (PE). Patients and methods: We studied 127 consecutive outpatients with clinically suspected PE. The diagnosis of PE was based on a clinical probability pretest for PE and a strict protocol of imaging studies. A plasma sample to measure the levels of tPA and D-dimer was obtained at enrollment. Diagnostic accuracy for tPA and D-dimer was determined by the area under the receiver operating characteristic (ROC) curve. Sensitivity, specificity, predictive values, and the diagnostic utility of tPA with a cutoff of 8.5 ng/mL and D-dimer with a cutoff of 500 ng/mL, were calculated for PE diagnosis. Results: PE was confirmed in 41 patients (32 %). Areas under ROC curves were 0.86 for D-dimer and 0.71 for tPA. The sensitivity/negative predictive value for D-dimer using a cutoff of 500 ng/mL, and tPA using a cutoff of 8.5 ng/mL, were 95 % (95 % CI, 88–100 %)/95 % (95 % CI, 88–100 %) and 95 % (95 % CI, 88–100 %)/94 %), respectively. The diagnostic utility to exclude PE was 28.3 % (95 % CI, 21–37 %) for D-dimer and 24.4 % (95 % CI, 17–33 %) for tPA. Conclusions: The tPA with a cutoff of 8.5 ng/mL has a high sensitivity and negative predictive value for exclusion of PE, similar to those observed for the VIDAS D-dimer with a cutoff of 500 ng/mL, although the diagnostic utility was slightly higher for the D-dimer.

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The L-Arginine: Nitric Oxide Pathway Contributes to the Acute Release of Tissue Plasminogen Activator in vivo in Man

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(97)87918-1 ◽

1998 ◽

Vol 31 (2) ◽

pp. 442A

Author(s):

D Newby

Keyword(s):

Nitric Oxide ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Tissue Plasminogen ◽

Nitric Oxide Pathway

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Desmopressin Stimulates Parallel Norepinephrine and Tissue Plasminogen Activator Release in Normal Subjects and Patients with Diabetes Mellitus

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642768 ◽

1988 ◽

Vol 59 (02) ◽

pp. 269-272 ◽

Cited By ~ 13

Author(s):

M B Grant ◽

C Guay ◽

R Lottenberg

Keyword(s):

Diabetes Mellitus ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Time Course ◽

Vascular Endothelial Cells ◽

Normal Subjects ◽

Plasma Norepinephrine ◽

Endogenous Catecholamine ◽

Tissue Plasminogen ◽

Patients With Diabetes

SummaryDesmopressin acetate administration markedly stimulates release of tissue plasminogen activator (t-PA) from vascular endothelial cells. The mechanism for this effect is unknown. Because infusion of epinephrine has been shown to increase t-PA levels, we examined the role of endogenous catecholamine mediation of t-PA release by desmopressin. Intravenous desmopressin acetate (0.3 μg/kg) was infused over 30 min in 9 controls and 11 subjects with diabetes mellitus, a condition associated with abnormalities of the fibrinolytic system. Plasma was collected in the supine, overnight fasted state at 15 min intervals (0-60 min) for measurement of t-PA activity, t-PA antigen and fractionated catecholamines. t-PA activity peaked at 30-45 min and subsequently decreased. The norepinephrine levels paralleled the t-PA activity. t-PA activity increased 10-fold from 0.14 ± .12 to 1.49 ± 0.79 IU/ml (Mean ± SD) and plasma norepinephrine increased 2- fold from 426 ± 90 to 780 ± 292 pg/ml. However, epinephrine and dopamine levels did not change significantly. The response to desmopressin of control and diabetic subjects was not shown to differ and their data were combined. We conclude that desmopressin increases plasma norepinephrine in addition to t-PA and that the parallel time course of change suggests a possible role for norepinephrine in mediating endothelial cell t-PA release.

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A Collaborative Study to Establish the 2nd International Standard for Tissue Plasminogen Activator (t-PA)

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646067 ◽

1987 ◽

Vol 58 (04) ◽

pp. 1085-1087 ◽

Cited By ~ 23

Author(s):

P J Gaffney ◽

A D Curtis

Keyword(s):

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Collaborative Study ◽

Chinese Hamster ◽

World Health ◽

Clot Lysis ◽

Expert Committee ◽

Single Chain ◽

International Standard ◽

Tissue Plasminogen

SummaryAn international collaborative study involving ten laboratories located in eight different countries was undertaken in order to replace the current International Standard (I.S.) for tissue plasminogen activator (t-PA). Two lyophilised candidate preparations of high purity were assessed in comparison with the current I.S. for t-PA using only a clot lysis assay. One preparation (coded 861670) was purified from a cultured melanoma cell supernatant and was about 98% single chain t-PA while the other preparation (coded 861624) was derived from Chinese hamster ovary (CHO) cells following DNA recombinant procedures and was 75% single chain t-PA.Both candidate preparations of t-PA compared in quite a satisfactory manner with the current I.S. from the viewpoint of the biometrics of parallel line bioassays and both preparations were quite stable for long periods at low temperatures and stable from up to 1 month at temperatures of 20° and 38° C. Both fultil the criteria to serve as a satisfactory Znd International Standard for t-PA. The Fibrinolysis Subcommittee of the International Committee for Thrombosis and Haemostasis recommended the melanoma source t-PA (861670) as the next I.S. in order to maintain continuity with the 1st I.S. which was also a melanomatype preparation. The data from the ten laboratories indicated that each ampoule of the new proposed standard contains 850 international units of t-PA activity by the clot lysis assay. It is planned to present the results of this study to the Expert Committee on Biological Standardization of the World Health Organization at its next meeting and to request that the preparation of t-PA, coded 861670, be established as the 2ndlnternational Standard for t-PA.

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Coagulation and Fibrinolytic Activity in Behçet's Disease

Thrombosis and Haemostasis ◽

10.1055/s-0038-1646409 ◽

1991 ◽

Vol 66 (03) ◽

pp. 292-294 ◽

Cited By ~ 57

Author(s):

K K Hampton ◽

M A Chamberlain ◽

D K Menon ◽

J A Davies

Keyword(s):

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Behçet’S Disease ◽

Fibrinolytic Activity ◽

Behcet’S Disease ◽

Behçet's Disease ◽

Plasminogen Activator Inhibitor ◽

Behcet's Disease ◽

Tissue Plasminogen ◽

Von Willebrand

SummaryCoagulation and fibrinolytic activities were studied in 18 subjects with Behçet's disease and compared with results from 14 matched control patients suffering from sero-negative arthritis. Significantly higher plasma concentrations (median and range) were found in Behçet's patients for the following variables: fibrinogen 3.7 (1.7-6.9) vs 3.0 (2.0-5.1) g/1, p <0.05; von Willebrand factor antigen, 115 (72-344) vs 74 (60-119)%, p <0.002; plasminogen activator activity (106/ECLT2) 219 (94-329) vs 137 (78-197) units, p <0.002; tissue plasminogen activator inhibitor (t-PA-I) activity, 9.1 (5.5-19.3) vs 5.1 (1.8-12.0) IU/ml, p <0.002; and PAI-1 antigen, 13.9 (4.5-20.9) vs 6.4 (2.4-11.1) ng/ml, p <0.002. Protein C antigen was significantly lower: 97 (70-183) vs 126 (96-220)%, p <0.02. No differences were observed in antithrombin III activity or antigen, factor VIII coagulant activity, fibrinopeptides A and Bβ15-42, plasminogen, α-2-antiplasmin, functional and immunological tissue-plasminogen activator, thrombin-antithrombin complexes and D-dimer. Levels of tissue plasminogen activator inhibitor (activity and antigen) correlated with disease activity while fibrinogen and von Willebrand factor concentrations did not. Seven of the 18 subjects with Behçet's disease had suffered thrombotic events but it was not possible to distinguish these from the 11 patients without thrombosis using the assays performed. The results suggest the abnormal fibrinolytic activity in Behçet's disease is due to increased inhibition of tissue plasminogen activator. No abnormality of coagulation or fibrinolytic activity specific to Behçet's disease was detected.

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