Fibrolase, an Active Thrombolytic Enzyme in Arterial and Venous Thrombosis Model Systems

1996 ◽  
pp. 427-438 ◽  
Author(s):  
F. S. Markland
Keyword(s):  
Venous Thrombosis ◽  
Model Systems ◽  
Thrombosis Model

Acyl-Enzymes as Thrombolytic Agents in Dog Models of Venous Thrombosis and Pulmonary Embolism

1984 ◽  
Vol 51 (02) ◽  
pp. 248-253 ◽  
Author(s):  
R J Dupe ◽  
P D English ◽  
R A G Smith ◽  
J Green
Keyword(s):  
Pulmonary Embolism ◽  
Side Effects ◽  
Venous Thrombosis ◽  
Active Site ◽  
Acute Pulmonary Embolism ◽  
Quantitative Model ◽  
Beagle Dog ◽  
Thrombosis Model ◽  
Derivatives Of

SummaryA quantitative model of venous thrombosis in the beagle dog is described. The model was adapted to permit ageing of isolated experimental clots in vivo. A model of acute pulmonary embolism in this species is also described. In the venous thrombosis model, infusion of streptokinase (SK) or SK-activated human plasmin gave significant lysis but bolus doses of SK. plasmin complex were ineffective. Active site anisoylated derivatives of SK. plasminogen complex, SK-activated plasmin and activator-free plasmin were all active when given as bolus doses in both models. At lytic doses, the acyl-enzymes caused fewer side-effects attributable to plasminaemia than the corresponding unmodified enzymes.

Antithrombotic Properties of a Truncated Recombinant Tissue Factor Pathway Inhibitor in an Experimental Venous Thrombosis Model

1993 ◽  
Vol 23 (1) ◽  
pp. 112-117 ◽  
Author(s):  
Jan Holst ◽  
Bengt Lindblad ◽  
David Bergqvist ◽  
Ole Nordfang ◽  
Per B. Østergaard ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Thrombosis Model ◽  
Tissue Factor Pathway

Thrombolysis with Systemically Administered t-PA in a New Venous Thrombosis Model

1989 ◽  
Vol 99 (1) ◽  
pp. 100???104 ◽  
Author(s):  
Richard E. Hayden ◽  
Patrick W. McLear ◽  
John G. Phillips ◽  
Steven M. Dawson
Keyword(s):  
Venous Thrombosis ◽  
Thrombosis Model

Reversal of anticoagulant effects of edoxaban, an oral, direct factor Xa inhibitor, with haemostatic agents

2012 ◽  
Vol 107 (02) ◽  
pp. 253-259 ◽  
Author(s):  
Toshio Fukuda ◽  
Yuko Honda ◽  
Chikako Kamisato ◽  
Toshiro Shibano ◽  
Yoshiyuki Morishima
Keyword(s):  
Venous Thrombosis ◽  
Prothrombin Complex Concentrate ◽  
Bleeding Time ◽  
Factor Viia ◽  
Thrombus Formation ◽  
Factor Xa ◽  
Factor Xa Inhibitor ◽  
Direct Factor ◽  
Thrombosis Model ◽  
Haemostatic Agents

SummaryEdoxaban, an oral, direct factor Xa inhibitor, has a similar or low incidence of bleeding events compared with other anticoagulants in clinical trials. Therefore, agents to reverse the anticoagulant effects of edoxaban could be desirable in emergency situations. In this study, the reversal effects of haemostatic agents were determined on prothrombin time (PT) prolongation in vitro and bleeding time prolongation in vivo by edoxaban. PT using human plasma was measured in the presence of edoxaban at therapeutic and excess concentrations with the haemostatic agents, prothrombin complex concentrate (PPSB-HT), activated prothrombin complex concentrate (Feiba), and recombinant factor VIIa (rFVIIa). In rats, rFVIIa and Feiba was given during intensive anticoagulation with edoxaban. The haemostatic effect was evaluated in a model of planta template bleeding and a potential prothrombotic effect was evaluated in a venous thrombosis model. PPSB-HT, Feiba, and rFVIIa concentration-dependently shortened PT prolonged by edoxaban. Among these, rFVIIa and Feiba showed potent activities in reversing the PT prolongation by edoxaban. rFVIIa (1 and 3 mg/kg, i.v.) and Feiba (100 U/kg, i.v.) significantly reversed edoxaban (1 mg/kg/h)-induced prolongation of bleeding time in rats. In a rat venous thrombosis model, no potentiation of thrombus formation was observed when the highest dose (3 mg/kg) of rFVIIa was added to edoxaban (0.3 and 1 mg/kg/h) compared with the control. The present study indicated that rFVIIa, Feiba, and PPSB-HT have the potential to be reversal agents for edoxaban.

The antithrombotic and haemostatic effects of LASSBio-752: a synthetic, orally active compound in an arterial and venous thrombosis model in rats

2017 ◽  
Vol 69 (10) ◽  
pp. 1374-1380 ◽  
Author(s):  
Flávia S. Frattani ◽  
Lidia M. Lima ◽  
Eliezer J. Barreiro ◽  
Russolina B. Zingali
Keyword(s):  
Venous Thrombosis ◽  
Active Compound ◽  
Thrombosis Model ◽  
Orally Active

A quantitative venous thrombosis model with stasis based on vascular lesion

1989 ◽  
Vol 53 (2) ◽  
pp. 197-201 ◽  
Author(s):  
Rodolfo Pescador ◽  
Roberto Porta ◽  
Angelo Conz ◽  
Marisa Mantovani
Keyword(s):  
Venous Thrombosis ◽  
Vascular Lesion ◽  
Thrombosis Model

Absence of Potentiation with Murine Antiplatelet GPIIb/IIIa Antibody of Thrombolysis with Recombinant Tissue-Type Plasminogen Activator (rt-PA) in a Canine Venous Thrombosis Model

1989 ◽  
Vol 61 (01) ◽  
pp. 093-096 ◽  
Author(s):  
D Spriggs ◽  
H K Gold ◽  
Y Hashimoto ◽  
E Van Houtte ◽  
J Vermylen ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Venous Thrombosis ◽  
Plasminogen Activator ◽  
Femoral Vein ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Thrombosis Model ◽  
Type Plasminogen Activator ◽  
Coronary Artery Thrombosis ◽  
Canine Coronary Artery

SummaryF(ab’)2 fragments of a murine monoclonal anti-platelet GPIIb/ IIIa antibody (7E3) are a potent platelet aggregation inhibitor, which in a canine coronary artery thrombosis model accelerate lysis with recombinant tissue-type plasminogen activator (rt-PA) and prevent reocclusion (7).In the present study, we have investigated the potential value of platelet aggregation inhibition as adjunctive therapy to lysis of venous thrombi, by measuring the thrombolytic potency of 7E3- F(ab’)2 and rt-PA used alone or in combination, in dogs with a 125I-fibrin labeled femoral vein thrombus. The dose-response of thrombolysis with rt-PA infused over 4 hours was linear: doses of 0.075 mg/kg, 0.15 mg/kg and 0.3 mg/kg produced 37 ± 3, 57 ± 11 and 83 ± 4% lysis respectively, against a background value of 20 ± 2%. With F(ab’)2 fragments of 7E3 given as a bolus of 1.2 mg/ kg, which saturated 70% of the platelet GPIIb/IIIa receptors and prolonged the bleeding to more than 30 min, lysis was not significantly increased over background. Combination of 0.3 or 0.6 mg/kg of 7E3-F(ab’)2 with either 0.03 or 0.06 mg/kg of rt-PA did not produce more lysis than obtained with a comparable dose of rt-PA alone. No significant changes in plasma fibrinogen or α2- antiplasmin were observed with either agent alone or with the combination. It is concluded that extensive inhibition of platelet aggregation does not potentiate the thrombolytic effect of rt-PA in this venous thrombosis model.

Fibrin Specific Thrombolysis by Two-Chain Urokinase-Type Plasminogen Activator Cleaved after Arginine 156 by Thrombin

1990 ◽  
Vol 64 (03) ◽  
pp. 426-432 ◽  
Author(s):  
David M Abercrombie ◽  
Bruce Buchinski ◽  
Kathleen A Salvato ◽  
Gerald F Vovis ◽  
David C Stump ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Thrombolytic Agent ◽  
Chain Molecule ◽  
Amidolytic Activity ◽  
Linear Dose ◽  
Thrombosis Model ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Dose Responses

SummaryScu-PA was cleaved by thrombin after arginine-156 to yield a two-chain molecule with low amidolytic activity and resistance to cleavage by plasmin. 125I-fibrin-labeled clots were dissolved in vitro by thrombin-cut scu-PA, but only at concentrations 10- to 50-fold greater than that needed for scu-PA. Three hours of incubation produced 100, 80, and 31% lysis with 100, 50, and 25 pg/ml thrombin-cut scu-PA. Thrombin-cut scu-PA, scu-PA, and tcu-PA yielded linear dose responses in the rabbit jugular venous thrombosis model. The dose required to reach 40% lysis was 2 mg/kg for scu-PA, 3 mg/kg for tcu-PA, and 4 mg/kg for thrombin-cut scu-PA. No significant consumption of fibrinogen or alpha2-antiplasmin levels was observed with thrombin-cut scu-PA while the level of fibrinogen and alpha2-antiplasmin decreased to about 50 and 40%, respectively, with scu-PA and to less than 10% of baseline with tcu-PA. Thus, while less potent than scu-PA, thrombin-cut scu-PA appears to be a more fibrin-specific thrombolytic agent than scu-PA.

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