Plasma Inhibitors of the Components of the Fibrinolytic Pathway in Man

Schreiber, Alan D.; Kaplan, Allen P.; Austen, K. Frank

doi:10.1172/jci107312

Cited by 66 publications

(29 citation statements)

References 17 publications

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“…thrombin (26), kallikrein (27,17), and trypsin (28), form a complex in which the enzymes retain their ability to degrade low molecular weight substrates while their proteolytic activity is lost. In contrast, Cd inactivator inhibits the proteolytic and esterolytic actions of kallikrein equally (23,29 (Fig. 5) with antikallikrein antibody indicate that kallikrein incubated with plasma produces a new species distinct from free kallikrein but with migration similar to Cl inactivator, detected by a specific antibody.…”

Section: Discussionmentioning

confidence: 93%

“…Harpel (22) was unable to separate the kallikrein from factor XI by isoelectric focusing, acrylamide gel electrophoresis, or G-200 Sephadex. Schreiber, Kaplan, and Austen (23) found that the isoelectric points of kallikrein, plasminogen proactivator, and factor XI are a few tenths pH apart and a kallikrein preparation demonstrated a broad band from pH 7.5 to 8.9 after focusing (24). Prekallikrein purified by Kaplan, Kay, and Austen (24) contained IgG as detected by radial immunodiffusion.…”

Section: Discussionmentioning

confidence: 99%

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Immunochemical Studies of Plasma Kallikrein

Bagdasarian¹,

Lahiri²,

Talamo³

et al. 1974

J. Clin. Invest.

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A B S T R A C T A monospecific antibody against humanplasma kallikrein has been prepared in rabbits with kallikrein further purified to remove gamma globulins. The antisera produced contained antikallikrein and also anti-IgG, in spite of only 8% contamination of kallikrein preparation with IgG. The latter antibody was removed by adsorption of antisera with either Fletcher factordeficient plasma or with purified IgG. Both kallikrein and prekallikrein (in plasma) cross-react with the antibody with no apparent difference between the precipitation arcs developed during immunoelectrophoresis and no significant difference in reactivity when quantified by radial immunodiffusion.Kallikrein antibody partially inhibits the esterolytic and fully inhibits the proteolytic activity of kallikrein. In addition, the antibody inhibits the activation of prekallikrein, as measured by esterase or kinin release. The magnitude of the inhibition is related to the molecular weight of the activator used. Thus, for the four activators tested, the greatest inhibition is observed with kaolin and factor XIIA, while large activator and the low molecular weight prekallikrein activators are less inhibited.With

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Immunochemical Studies of Plasma Kallikrein

Bagdasarian¹,

Lahiri²,

Talamo³

et al. 1974

J. Clin. Invest.

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“…Kininogen was located antigenically by electroimmunodiffusion (counterimmunoelectrophoresis), performed as described by Schreiber et al (37). The precipitin lines were graded by inspection on a 0-4+ scale.…”

Section: Methodsmentioning

confidence: 99%

Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways.

Colman¹,

Bagdasarian²,

Talamo³

et al. 1975

J. Clin. Invest.

322

194

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A B S T R A C T An asymptomatic woman (Ms. \Vil-liams) was found to have a severe abnormality in the surface-activated intrinsic coagulation, fibrinolvtic, and kinin-generating pathways. Assays for known coagulation factors were normal while Fletcher factor (prekallikrein) was 45%, insufficient to account for the observed markedly prolonged partial thromboplastin time. Plasminogen proactivator was present at 20% of normal levels and addition of highly purified plasminogen proactivator containing 10% plasminogen activator partially corrected the coagulation and fibrinolytic abnormalities but not the kinin-generating defect. This effect was due to its plasminogen activator content. In addition, Williams trait plasma failed to convert prekallikrein to kallikrein or release kiniin upon incubation with kaolin. Kininogen

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“…2 Other proteins known to influence fibrinolysis are, for instance, lipoprotein(a), 25 which competes with plasminogen for binding to fibrinogen; vitronectin, 26 which binds to PAI-1 and stabilizes it; histidine-rich glycoprotein, which binds to plasminogen and modulates plasminogen bioavailability for plasmin generation 27 ; and the plasmin inhibitors ␣ 2 -macroglobulin, ␣ 1 -antitrypsin, and C1 inhibitor. 28 We are currently examining possible genetic factors influencing CLT through quantitative trait loci analysis in an extended thrombophilic pedigree. 23 Part of the unexplained variation may be the result of lack of fit of the model as the linear regression model assumes a linear relation between the proteins and CLT, which may not always be completely accurate.…”

Section: Fibrinolysis and Risk Of Venous Thrombosismentioning

confidence: 99%

Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1

Meltzer

Lisman

Groot

et al. 2010

Blood

326

272

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Elevated plasma clot lysis time (CLT) increases risk of venous and arterial thrombosis. It is unclear which fibrinolytic factors contribute to thrombosis risk. In 743 healthy control subjects we investigated determinants of CLT. By comparison with 770 thrombosis patients, we assessed plasma levels of fibrinolytic proteins as risk factors for a first thrombosis. Plasminogen activator inhibitor-1 (PAI-1) levels were the main determinants of CLT, followed by plasminogen, thrombin-activatable fibrinolysis inhibitor (TAFI), prothrombin, and ␣2-antiplasmin. Fibrinogen, factor VII, X, and XI contributed minimally. These proteins explained 77% of variation in CLT. Levels of the fibrinolytic factors were associated with thrombosis risk (odds ratios, highest quartile vs lowest, adjusted for age, sex, and body mass index: 1.6 for plasminogen, 1.2 for ␣2-antiplasmin, 1.6 for TAFI, 1.6 for PAI-1, and 1.8 for tissue plasminogen activator [t-PA]). Adjusting for acute-phase proteins attenuated the risk associated with elevated plasminogen levels. The risk associated with increased t-PA nearly disappeared after adjusting for acute-phase proteins and endothelial activation. TAFI and PAI-1 remained associated with thrombosis after extensive adjustment. In conclusion, CLT reflects levels of all fibrinolytic factors except t-PA. Plasminogen, TAFI, PAI-1, and t-PA are associated with venous thrombosis. However, plasminogen and t-PA levels may reflect underlying risk factors. (Blood. 2010;116(1):113-121)

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Plasma Inhibitors of the Components of the Fibrinolytic Pathway in Man

Cited by 66 publications

References 17 publications

Immunochemical Studies of Plasma Kallikrein

Immunochemical Studies of Plasma Kallikrein

Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways.

Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1

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