Mechanism of Action of Synthetic Fibrinolytic Compounds

1970 ◽  
Vol 24 (03/04) ◽  
pp. 495-506
Author(s):  
W Baumgarten ◽  
L. I Priester ◽  
D. W Stiller ◽  
A. E William Duncan
Keyword(s):  
Mechanism Of Action ◽  
Plasma Proteins ◽  
Fibrinolytic Activity ◽  
Fibrin Clot ◽  
Plasma Clot ◽  
Active Compounds ◽  
Preformed Plasma ◽  
Fibrinolytic Potential ◽  
Fibrinolytic Compounds

SummaryThe mechanism of dissolution of a preformed plasma clot was explored.Our experiments showed clearly that the purified fibrin clot, made by extensive washing of a plasma clot, was resistant to lysis and that the fibrinolytic potential of the active fibrinolytic compounds was related to the presence of other plasma proteins in addition to fibrinogen.The activation of the fibrinolytic precursors was reversible inasmuch as removal of the fibrinolytic compounds negated the fibrinolytic activity of the protein-fibrinolytic compound mixture.Antifibrinolytic compounds which had been shown to interfer with fibrinolysis by streptokinase-activated plasminogen inhibited dissolution of the preformed plasma clot by fibrinolytically active compounds.The fibrinolytic potential of fibrinolytic compounds was additive; however, no apparent synergism was observed.The implication of these results to the mechanism of synthetic fibrinolysis was discussed.

scholarly journals THE FIBRINOLYTIC ACTIVITY OF HEMOLYTIC STREPTOCOCCI

1933 ◽  
Vol 58 (4) ◽  
pp. 485-502 ◽  
Author(s):  
William S. Tillett ◽  
R. L. Garner
Keyword(s):  
Fibrinolytic Activity ◽  
Bacterial Species ◽  
Surrounding Medium ◽  
Fibrin Clot ◽  
Animal Origin ◽  
Complete Dissolution ◽  
Experimental Conditions ◽  
Plasma Clot ◽  
Human Fibrinogen ◽  
Normal Human

Broth cultures of hemolytic streptococci derived from patients are capable of rapidly liquefying normal human fibrin clot. The active fibrinolytic principle is also contained in sterile, cell-free filtrates of broth cultures. The degree of activity of filtrates parallels the activity of whole broth cultures sufficiently closely to indicate that large amounts of the fibrinolytic substance are freely excreted into the surrounding medium and pass readily through Berkefeld V, Seitz, and Chamberland filters. The occurrence of fibrinolysis is most strikingly observed when plasma or fibrinogen is mixed with active cultural material before clot formation is effected. Under the standard experimental conditions described, complete dissolution of human plasma clot (whole oxalated plasma + CaCl2) occurs in about 10 minutes; complete dissolution of human fibrinogen clot (chemically isolated fibrinogen + thrombin) takes place in about 2 minutes. Titration of filtrate activity is recorded in Table IV. Twenty-eight strains of Streptococcus hemolyticus, isolated from patients suffering from various manifestations of streptococcus infection, have been tested for the capacity to liquefy fibrin clot. Broth cultures of all of the strains induced fibrinolysis. Of 18 strains of Streptococcus hemolyticus of animal origin, only three were capable of causing dissolution of clot. Completely negative results were obtained with 38 strains of other bacterial species. The list is presented on pages 492 and 493. The plasma of many patients recovered from acute hemolytic streptococcus infections, when clotted in the presence of active cultures, is highly resistant to fibrinolysis. Furthermore, serum, derived from patients whose plasma clot is resistant, often confers on normal plasma clot an antifibrinolytic property. One example of the resistance possessed by the blood of convalescent patients is presented in this report. A second paper, now in preparation, will give in detail a large number of observations on the relation of infection to the development of resistance to the fibrinolytic activity of hemolytic streptococci. In contrast to the susceptibility of normal human fibrin clot to liquefaction by active culture, normal rabbit fibrin clot is totally resistant to dissolution when tested under comparable conditions. The insusceptibility of rabbit fibrin clot is manifest provided the coagulum is composed of rabbit constituents. When human thrombin is used to clot rabbit plasma or fibrinogen in the presence of active cultures, fibrinolysis is not prohibited. The rôle of thrombin in determining the resistance or susceptibility of rabbit fibrin to dissolution offers a suggestive approach to problems relating to the underiving mechanism.

The Preparation and Evaluation of a Standardized Fibrin Plate for the Assessment of Fibrinolytic Activity

1970 ◽  
Vol 23 (02) ◽  
pp. 202-210 ◽  
Author(s):  
R Bishop ◽  
H Ekert ◽  
G Gilchrist ◽  
E Shanbrom ◽  
L Fekete
Keyword(s):  
Test Specimen ◽  
Fibrinolytic Activity ◽  
Clinical Laboratory ◽  
Fibrin Clot ◽  
Fibrinolytic Enzyme ◽  
Agarose Gel ◽  
Fibrin Plate ◽  
Percent Concentration ◽  
Human Plasminogen ◽  
Preparation And Evaluation

SummaryA new fibrin plate technic for evaluating components of the fibrinolytic system has been developed. It provides quick, accurate, and easily interpreted results for the fibrinolytic profile. The standardized human plasminogen-free fibrin plates can be produced in bulk and stored for prolonged periods of time. A test specimen placed in a well punched in the buffered agarose gel diffuses into the agar and lyses the fibrin clot, forming a clear reaction zone. The zone diameter is directly proportional to the log of the percent concentration of available fibrinolytic enzyme in the specimen. The plates may be used to quantitate total plasminogen, and estimate available plasmin and active plasmin. A good correlation between results obtained using these fibrin plates and caseinolytic methods was found. Performance and interpretation of tests of fibrinolysis done on these new fibrin plates indicate that it may be the most sensitive technic available for clinical laboratory work.

scholarly journals Fibrin Clot Formation and Lysis in Plasma

2020 ◽  
Vol 3 (4) ◽  
pp. 67
Author(s):  
Julie Brogaard Larsen ◽  
Anne-Mette Hvas
Keyword(s):  
Fibrinolytic Activity ◽  
Research Laboratory ◽  
Ex Vivo ◽  
Fibrin Clot ◽  
Clot Formation ◽  
Coagulation Assays ◽  
Fibrin Formation ◽  
Over Time ◽  
Routine Coagulation

Disturbance in the balance between fibrin formation and fibrinolysis can lead to either bleeding or thrombosis; however, our current routine coagulation assays are not sensitive to altered fibrinolysis. The clot formation and lysis assay is a dynamic plasma-based analysis that assesses the patient’s capacity for fibrin formation and fibrinolysis by adding an activator of coagulation as well as fibrinolysis to plasma and measuring ex vivo fibrin clot formation and breakdown over time. This assay provides detailed information on the fibrinolytic activity but is currently used for research only, as the assay is prone to inter-laboratory variation and as it demands experienced laboratory technicians as well as specialized personnel to validate and interpret the results. Here, we describe a protocol for the clot formation and lysis assay used at our research laboratory.

ACTIVATION PATHWAYS OF PLASMINOGEN BY UROKINASE AND TISSUE PLASMINOGEN ACTIVATOR IN THE PLASMA OR CLOTTED PLASMA: COMAPRISON WITH PURIFIED SYSTEMS

1987 ◽  
Author(s):  
Y Makino ◽  
M Yoshida ◽  
Y Takada ◽  
A Takada
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Fibrin Clot ◽  
Activation Process ◽  
Plasma Clot ◽  
Native Form ◽  
Tissue Plasminogen ◽  
Cross Linkage ◽  
Activation Pathways

The activation pathways of a native plasminogen (Glu-plg) were studied in the plasma and purified systems. When purified Glu-plg was activated by urokinase (UK) or tissue plasminogen activator (t-PA), the activation of Glu-plg proceeded very slowly in the presence of fibrinogen, but rapidly in the presence of non crosslinked or cross-linked fibrin. Little formation of modified pig (Lys-plg) was observed in the presence of fibrinogen, but significant amounts of Lys-plg were formed in the presence of fibrin clot. The addition of α2antiplasmin (α2AP) to the mixture of Glu-plg, UK or t-PA, and fibrinogen or fibrin resulted in little formation of Lys-plg in the presence of fibrinogen but significant formation of Lys-plg in the presence of non cross-linked or cross linked fibrin. Alphapantiplasmin did not prevent the formation of Lys-plg from Glu-plg by plasmin in the presence of fibrin regardless of possible cross-linkage of α2AP to fibrin. In contrast to purified system, the activation of Glu-plg by UK or t-PA in the presence of plasma clot resulted in little formation of Lys pig The addition of thrombin and Ca++ to the plasma activated by UK or t-PA resulted in little formation of Lys-plg. These results suggest that Glu-plg was mainly directly activated by UK or t-PA to Glu-plasmin (then Lys-plasmin) in the plasma or plasma clot (non cross-linked or cross-linked), and that some of Glu-plg was converted to Lys-plg by preformed plasmin after UK or t-PA induced activation of Glu-plg in the presence of fibrin. It should be stressed that not all the molecules of Glu-plg were converted to Lys-plg in the presence of fibrin before their activation by activators. Some amounts of Glu-plg were present throughout the activation process in its native form.

Effects on longevity extension and mechanism of action of carnosic acid in Caenorhabditis elegans

2019 ◽  
Vol 10 (3) ◽  
pp. 1398-1410 ◽  
Author(s):  
Chunxiu Lin ◽  
Xiaoying Zhang ◽  
Jie Xiao ◽  
Qiqi Zhong ◽  
Yong Kuang ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Mechanism Of Action ◽  
Carnosic Acid ◽  
Active Compounds

The study offers methods and models for elucidating healthspan promotion and mechanism, valuable for studies of other naturally active compounds.

Hematologic response of fish to changes in gas or hydrostatic pressure

1980 ◽  
Vol 239 (1) ◽  
pp. R161-R167 ◽  
Author(s):  
E. Casillas ◽  
L. S. Smith ◽  
J. J. Woodward ◽  
B. G. D'Aoust
Keyword(s):  
Hydrostatic Pressure ◽  
Plasma Proteins ◽  
Fibrinolytic Activity ◽  
Coagulation System ◽  
Related Phenomenon ◽  
Protein Levels ◽  
Diffuse Intravascular Coagulation ◽  
Rapid Decompression ◽  
Increased Pressure ◽  
Increased Susceptibility

Hematologic changes were studied in fingering salmon after rapid decompression from combined or independent exposure to gas and hydrostatic pressure. After decompression, fingerling salmon saturated with excess gas under pressure (10.1-40.6 m of seawater) suffered a decrease in thrombocyte counts and fibrinogen, prolonged prothrombin (PT) times, and increased fibrinolytic activity, plasma proteins, and erythrocyte counts in proportion to severity of the dive. After decompression, fingerling salmon exposed to increased pressure experienced an increase in thrombocyte counts and available fibrinogen, shortened PT times, increased erythrocyte counts, and decreased plasma protein levels. It appeared that pressure causes activation of the blood coagulation system of fish. This activation may predispose the fish to increased susceptibility to bubble-induced diffuse intravascular coagulation after rapid decompression. Furthermore, hemoconcentration after decompression may be a pressure-related phenomenon and not a response to bubble-induced anoxia.

Effects of exercise and conditioning on clotting and fibrinolytic activity in men

1987 ◽  
Vol 62 (4) ◽  
pp. 1416-1421 ◽  
Author(s):  
E. W. Ferguson ◽  
L. L. Bernier ◽  
G. R. Banta ◽  
J. Yu-Yahiro ◽  
E. B. Schoomaker
Keyword(s):  
Fibrinolytic Activity ◽  
Blood Clotting ◽  
Degradation Products ◽  
Clot Lysis ◽  
Plasma Clot ◽  
Fitness Program ◽  
Fibrin Degradation Products ◽  
Before And After ◽  
Plasmin Inhibitor ◽  
Sedentary Subjects

Sixty healthy men in three physical fitness categories (sedentary, on no organized fitness program; joggers, running 5–15 miles/wk; and marathoners, running greater than 50 miles/wk) were evaluated for changes in blood clotting and fibrinolytic activity before and after maximum exercise on a treadmill according to the Bruce protocol. The rate of blood clotting, as measured by prothrombin times, partial thromboplastin times and thrombin times, was accelerated by exercise (all P less than 0.005). The ability of euglobulin clots and plasma clots to lyse incorporated 125I-fibrin, termed 125I-euglobulin clot lysis (IEL) and 125I-plasma clot lysis (IPCL), were used as indexes of fibrinolytic activity. Marathoners had greater increases in fibrinolytic activity with exercise (76% compared with 63% for joggers and 55% for sedentary subjects by IEL; 427% compared with 418% for joggers and 309% for sedentary subjects by IPCL; all P less than 0.05). Fibrin degradation products increased with exercise (P less than 0.005 for the total group of 60 subjects). The absolute concentrations of alpha 2-plasmin inhibitor, alpha 2-macroglobulin, and antithrombin III increased with exercise (all P less than 0.005), but when concentrations were corrected for acute shifts of plasma water during exercise, the quantity of these inhibitors actually decreased (all P less than 0.005). The changes in clotting assays with exercise were not significantly correlated with changes in whole blood lactate, blood pyruvate, or rectal temperatures. Fibrinolytic assays before and after exercise correlated poorly to moderately with blood lactates (IEL: r = 0.441 and r = 0.425, respectively; IPCL: r = 0.294 and r = 0.544, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Plasma Fibrin Clot Properties as Determinants of Bleeding Time in Human Subjects: Association with Histidine-Rich Glycoprotein

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Konstanty Szułdrzyński ◽  
Miłosz Jankowski ◽  
Daniel P. Potaczek ◽  
Anetta Undas
Keyword(s):  
Wound Healing ◽  
Bleeding Time ◽  
Human Subjects ◽  
Fibrin Clot ◽  
Skin Wound ◽  
Clot Lysis ◽  
Skin Wound Healing ◽  
Plasma Clot ◽  
Primary Hemostasis ◽  
Complex Relationships

Aims. Fibrin formation and histidine-rich glycoprotein (HRG) are involved in primary hemostasis and wound healing. Little is known regarding the relationship of clot characteristics, bleeding time, and wound healing. Methods and Results. We studied 154 patients with coronary artery disease (CAD) and 154 subjects free of CAD matched for age, obesity, and current smoking. We evaluated bleeding time (BT) using standardized skin incisions on a forearm, along with plasma clot permeability (Ks), clot lysis time (CLT), and histidine-rich glycoprotein (HRG). Compared with controls, BT was 45% shorter in CAD cases. CAD patients had 32% lower Ks and 17% longer CLT as well as 50% lower HRG compared with controls (all p<0.001). After adjusting for potential confounders, Ks and HRG levels were independent predictors of prolonged BT in CAD patients (OR 23.70, 95% CI 4.65-120.8 and OR 10.27, 95% CI 2.05-51.31, respectively) and controls (OR 10.89, 95% CI 2.31-51.11 and OR 4.54, 95% CI 1.07-19.27, respectively). Scar formation (n=79, 25.6%) was independently predicted by both short and prolonged BT in CAD cases (OR 21.87, 95% CI 7.41-64.55 and OR 10.17, 95% CI 2.88-35.97) and controls (OR 5.94, 95% CI 2.29-15.41 and OR 14.76, 95% CI 4.29-50.77, respectively). Conclusions. The study shows that plasma fibrin clot density and HRG may influence BT and that appropriate skin wound healing is associated with medium BT. Translational Perspective. Elucidation of the complex relationships between plasma fibrin clot phenotype and wound healing might have important practical implications.

scholarly journals Identification of Fibrin Clot-Bound Plasma Proteins

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e41966 ◽  
Author(s):  
Simone Talens ◽  
Frank W. G. Leebeek ◽  
Jeroen A. A. Demmers ◽  
Dingeman C. Rijken
Keyword(s):  
Plasma Proteins ◽  
Fibrin Clot

L-Lysine: A Modulator for the Relative Activity of High Molecular Weight (HMW) and Low Molecular Weight(LHW) Urokinase(UK)

1979 ◽  
Author(s):  
L.L. Shen ◽  
W.H. Holleman
Keyword(s):  
Molecular Weight ◽  
Caproic Acid ◽  
Fibrin Clot ◽  
Relative Activity ◽  
Test Tube ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Plasma Clot ◽  
Concentration Dependent Manner ◽  
The Difference

L-Lysine(Lys), in a concentration dependent manner, progressively inhibited UK-activated lysis of human plasma clots as demonstrated by Ploug test-tube method and elastometric measurements. Lys was more effective with HMW UK than LMW UK, and the effect of Lys with LMW UK from tissue culture and urine sources was the same. Epsilon amino caproic acid(EACA) and tranexamic acid(TXA) were stronger inhibitors but inhibited HMW and LMW UK-induced lysis to the same degree. Elastometric measurements showed that Lys inhibition was not due to its interference with the initial clotting process nor to the reduction of clot rigidity. Amidolytic assays using chromogenic substrates showed that Lys had no direct effect, on UK, and that Lys enhanced the activation of the native Glu-plasminogen(Pg) by LMW UK, but not the activation by HMW UK. When the substrate was human fibrin clots, Lys enhanced the lysis induced by LMW UK while the lysis induced by HMW UK was inhibited; however, the extent of enhancement and inhibition was limited. We concluded that the mode of Lys action is not identical to that of EACA or TXA, and that the stronger Lys inhibition of plasma clot lysis as compared to fibrin clot lysis is due to the potentiation of plasma fibrinolytic inhibitors by Lys. The difference In effect of Lys on HMW and LMW UK-induced lyels is likely due to a partial conformation change of Glu-Pg molecule upon Lys binding. The relatively moderate interaction of Lys with Glu-Fg results In a mildly modified UK substrate which reacts preferentially with the enzyme smaller in size.

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