The Effect of Sulfhydrylinhibitors and Glycine Derivatives on Fibrin  Polymerization and the Physical Strength of Fibrin in Plasma

Gormsen, J; Sivertsen, U

doi:10.1055/s-0038-1654841

Cited by 9 publications

(6 citation statements)

References 6 publications

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“…This has been previously shown by thromboelastograms of plasma clots from a patient congenitally deficient in Factor X I 1 1 (Beck, Duckert and Ernst, 1961). Gormsen and Silverntsen (1964) found the same thromboelastographic characteristics in plasma treated with various sulphydryl inhibitors. These authors did not demonstrate an effect on the urea solubility of clots with glycine-amide or glycine methyl ester.…”

Section: Discussionsupporting

confidence: 76%

The Mechanism of Enhanced Streptokinase‐Induced Clot Lysis following In‐vitro Factor‐XIII Inactivation

Henderson

Nussbaum

1969

Br J Haematol

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Summary. Factor‐XIII (fibrin stabilizing factor, FSF) activity in human plasma may be inhibited in vitro by a variety of sulphydryl inhibitors and by several derivatives of glycine. Incorporation of small amounts (40 units) of streptokinase (SK) into a clot formed from plasma after in vitro inactivation of Factor XIII, resulted in marked shortening of clot lysis times compared to controls without Factor‐XIII inactivation. Enhancement of SK‐induced clot lysis by the sulphydryl inhibitors is in part related to Factor‐XIII inactivation. Further acceleration of lysis is noted with concentrations greater than the minimal amount necessary for complete Factor‐XIII inhibition. At higher concentrations, clotting is delayed and ultimately completely inhibited. These reagents also produce marked changes on the thromboelastogram consistent with a weakened clot structure. No evidence to suggest increased plasminogen‐plasmin conversion, enhanced plasmin activity or inhibition of anti‐plasmin by sulphydryl inhibitors could be found. Glycine ethyl ester (GEE) incorporation results in marked enhancement of SK‐induced plasma clot lysis in vitro and pronounced changes on the thromboelastogram. The enhanced clot lysis is related to Factor‐XIII inhibition. No further acceleration of clot lysis was obtained once Factor‐XIII activity was completely inhibited. GEE alone shows an additional effect of inhibiting anti‐plasmin activity. Thus enhanced SK‐induced clot lysis following in vitro inhibition of Factor‐XIII activity with sulphydryl inhibitors and derivatives of glycine is considered to be due to the greater ease with which plasmin may act on a weakened clot. GEE, in addition to promoting the formation of a weaker clot, inhibits anti‐plasmin activity, and so further increases the relative effectiveness of streptokinase.

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Section: Discussionsupporting

confidence: 76%

The Mechanism of Enhanced Streptokinase‐Induced Clot Lysis following In‐vitro Factor‐XIII Inactivation

Henderson

Nussbaum

1969

Br J Haematol

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“…Quality criteria of urea treated fibrinogen: pH, ionic strength, and thrombin clottability (dilute thrombin solution, 10 NIH u/ml) were checked each time to be identical with a corresponding solution of untreated fibrinogen. Estimations of polymerization rate and degree were checked by random experiments (Gormsen & Sivertsen 1964). The urea concentration was always controlled after dialysis (urease method, Department of Clinical Chemistry, Sundby Hospital) and found to be from 0-3 x 10-4 moV1, concentrations which in the fibrin substrate of fibrin plates have no inhibitory effect on plasmin lysis.…”

Section: Methodsmentioning

confidence: 99%

Demonstration of Different D‐ and E‐Antigenic Intermediates During Plasmin Degradation of Non‐Stabilized and Stabilized Fibrin Clots

Gormsen

Feddersen

1973

Scandinavian Journal of Haematology

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The degradation scheme of stabilized and non‐stabilized (solubility criteria) human fibrin clots, as obtained by porcine plasmin and urokinase activation of human plasminogen, is illustrated by crossed immuno‐electrophoresis in agarose using antifibrinogen and monospecific anti‐D and anti‐E serum and is further characterized by Sephadex G 150 filtration and by sodium dodecyl sulphate polyacrylamide electrophoresis. Heat labile E‐antigenic fractions exhibiting slow migration in agarose appear early during digestion of fibrin and are especially characteristic for the degradation of stabilized fibrin, whereas only traces are found during degradation of non‐stabilized fibrin. They decrease in concentration and disappear as the final E‐antigenic fraction with distinct anodic mobility in agarose develops. The intermediary fractions are eluted by Sephadex G 150 filtration before the final plasmin resistant E‐fraction. Some of these intermediates may have a molecular weight from more than 50, 000 to around 250, 000, whereas the final E‐antigenic plasmin resistant has a molecular weight of 50, 000. The plasmin‐resistant heat‐labile D‐fragments found during digestion of non‐stabilized fibrin have a molecular weight of around 100, 000, whereas plasmin‐resistant D‐antigenic fractions found during degradation of stabilized fibrin have a molecular weight of around 190, 000, all molecular weights approximated (non‐reduced freeze dried Sephadex filtrates).

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“…Our data clearly indicate that in the presence of FSF, fibrin formed by ancrod is markedly more susceptible to plasmin degradation than fibrin formed by thrombin. This usually has been attributed solely to the fact that ancrod-formed fibrin is noncross-linked (24,29,47), since it has been shown that urea-soluble, noncross-linked clots are less resistant to lysis than crosslinked clots (48,49). In accord with these observations, results shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Mechanism of ancrod anticoagulation

Pizzo¹,

Schwartz²,

Hill³

et al. 1972

J. Clin. Invest.

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A B S T R A C T Fibrin formed in response to ancrod, reptilase, or thrombin was reduced by P-mercaptoethanol and examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was found that ancrod progressively and totally digested the a-chains of fibrin monomers at sites different than plasmin; however, further digestion of fibrin monomers by either reptilase or thrombin was not observed. Highly purified ancrod did not activate fibrin-stabilizing factor (FSF); however, the reptilase preparation used in these experiments, like thrombin, activated FSF and thereby promoted cross-link formation. Fibrin, formed by clotting purified human fibrinogen with ancrod, reptilase, or thrombin for increasing periods of time in the presence of plasminogen, was incubated with urokinase and observed for complete lysis. Fibrin formed by ancrod was strikingly more vulnerable to plasmin digestion than was fibrin formed by reptilase or thrombin. The lysis times for fibrin formed for 2 hr by ancrod, reptilase, or thrombin were 18, 89, and 120 min, respectively.Evidence was also obtained that neither ancrod nor reptilase activated human plasminogen. These results indicate that fibrin formed by ancrod is not cross-linked and has significantly degraded a-chains; as expected, ancrodformed fibrin is markedly susceptible to digestion by plasmin.

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The Effect of Sulfhydrylinhibitors and Glycine Derivatives on Fibrin Polymerization and the Physical Strength of Fibrin in Plasma

Cited by 9 publications

References 6 publications

The Mechanism of Enhanced Streptokinase‐Induced Clot Lysis following In‐vitro Factor‐XIII Inactivation

The Mechanism of Enhanced Streptokinase‐Induced Clot Lysis following In‐vitro Factor‐XIII Inactivation

Demonstration of Different D‐ and E‐Antigenic Intermediates During Plasmin Degradation of Non‐Stabilized and Stabilized Fibrin Clots

Mechanism of ancrod anticoagulation

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