Studies on the Participation of Hageman Factor in Fibrinolysis

1970 ◽  
Vol 24 (01/02) ◽  
pp. 001-009 ◽  
Author(s):  
R.P McDonagh ◽  
J.H Ferguson
Keyword(s):  
Cytochrome C ◽  
Plasminogen Activator ◽  
Specific Inhibition ◽  
Hageman Factor ◽  
One Stage ◽  
Marked Inhibition ◽  
Normal Plasma ◽  
Generation Test

SummaryThe specific inhibition of the kaolin-mediated Hageman factor activation by the polycations : lysozyme, spermine tetrahydrochloride, and cytochrome c was confirmed. These polycations were without any antiplasmin or antiplasminogen-activator activity when tested in a one-stage lysis system. However, marked inhibition of plasminogen-activator generation in normal plasma by these polycations was noted in the activator-generation test. The proposed role of Hageman factor as that of a lysokinase or indirect activator of plasminogen is supported by these experiments.

The Formation of Intermediate Product I in a Purified System The Role of Factor IX or of its Precursor and of a Hageman Factor-PTA Fraction

1961 ◽  
Vol 6 (02) ◽  
pp. 224-234 ◽  
Author(s):  
E. T Yin ◽  
F Duckert
Keyword(s):  
Intermediate Product ◽  
Factor Ix ◽  
Assay Method ◽  
Lag Phase ◽  
Factor X ◽  
Haemophilia B ◽  
Hageman Factor ◽  
One Stage ◽  
The One

Summary1. The role of two clot promoting fractions isolated from either plasma or serum is studied in a purified system for the generation of intermediate product I in which the serum is replaced by factor X and the investigated fractions.2. Optimal generation of intermediate product I is possible in the purified system utilizing fractions devoid of factor IX one-stage activity. Prothrombin and thrombin are not necessary in this system.3. The fraction containing factor IX or its precursor, no measurable activity by the one-stage assay method, controls the yield of intermediate product I. No similar fraction can be isolated from haemophilia B plasma or serum.4. The Hageman factor — PTA fraction shortens the lag phase of intermediate product I formation and has no influence on the yield. This fraction can also be prepared from haemophilia B plasma or serum.

Role of α2-Antiplasmin in Fibrin-Specific Clot Lysis with Single-Chain Urokinase-Type Plasminogen Activator in Human Plasma

1991 ◽  
Vol 65 (04) ◽  
pp. 394-398 ◽  
Author(s):  
P J Declerck ◽  
H R Lijnen ◽  
M Verstreken ◽  
D Collen
Keyword(s):  
Human Plasma ◽  
Plasminogen Activator ◽  
Clot Lysis ◽  
Minor Role ◽  
Single Chain ◽  
Plasma Clot ◽  
Normal Plasma ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

SummaryThe role of plasma α2-antiplasmin (α2-AP) in the fibrinspecificity of clot lysis by recombinant single-chain urokinase-type plasminogen activator (rscu-PA) and in the conversion of rscu-PA to its two-chain derivative (rtcu-PA, urokinase) was investigated in an in vitro human plasma clot lysis system. Fifty % lysis in 2 h of a 0.1 ml 125l-fibrin labeled human plasma clot immersed in 0.5 ml normal human plasma was obtained with 1.4 ± 0.15 µg/ml rscu-PA (mean ± SD, n = 8). This was associated with degradation of 23 ± 7% of fibrinogen and generation of 0.20 ± 0.09 µg/ml rtcu-PA. In α2-AP-depleted plasrna 50% clot lysis in 2 h required 2-fold less rscu-PA which was associated with 3-fold more extensive fibrinogen degradation and 2-fold more rtcu-PA generation. Fifty % lysis in? h, of a 0.1 ml α2-AP-depleted plasma clot, subriersed in 0.5 ml normal plasma, was obtained with 0.80 ± 0.05 µg/ml rscu-PA (n = 3, p <0.001 vs normal clot) and was associated with 17 ± 6% fibrinogen breakdown (p : 0.22 vs normal clot) and 0.08 ± 0.02 µg/ml rtcu-PA generation (p < 0.05 vs normal clot). In α2-AP-depleted plasma the equipotent rscu-PA concentration was 4-fold lower than in normal plasma and was associated with 3-fold more fibrinogen degradation and a similar extent of rtcu-PA generationThus, α2-AP in plasma contributes significantly to the fibrinspecificity of rscu-PA, primarily via prevention of conversion in plasma of rscu-PA to rtcu-PA. Clot associated α2-AP increases the resistance of the clot to lysis with rscu-PA, but plays an only minor role in the fibrin-specificity of clot lysis in normal plasma.

One-stage Assay for Hageman Factor (Factor XII). Further Studies on the Role of Hageman Factor in Blood Coagulation

1963 ◽  
Vol 09 (03) ◽  
pp. 557-569 ◽  
Author(s):  
C Haanen ◽  
John G. G Schoenmakers
Keyword(s):  
Factor Ix ◽  
Factor Xii ◽  
Charged Surface ◽  
Dilution Curve ◽  
Adsorbed State ◽  
Hageman Factor ◽  
High Affinity ◽  
One Stage ◽  
Glass Surfaces

SummaryA one stage assay for Hageman Factor (HF) activity is described. Maximal standardization was achieved by lyophilizing substrate plasma, cephalin suspension and standard reference plasma in small aliquots. A dilution curve was constructed, using a highly purified HF preparation. The assay is not completely specific and is invalidated by the presence of activated Factor IX and XI. So all materials to be tested were first adsorbed on Al(OH)3-gel to exclude Factor IX and possibly most of Factor XI.Purified activated HF still possesses a high affinity for glass surfaces, thus activation may not alter the molecule at the side of affinity for the glass surface. Moreover purified activated HF is still more active in the presence of glass thus in the adsorbed state. These observations support the idea that the so called activation of Hageman Factor is a reversible phenomenon, whereby the molecule unfolds and uncovers active groups as soon as it is adsorbed on a negatively charged surface.

Some Observations on the Rôle of Hageman Factor in Blood Coagulation

1961 ◽  
Vol 6 (02) ◽  
pp. 261-269 ◽  
Author(s):  
C Haanen ◽  
F Hommes ◽  
Gerdy Morselt
Keyword(s):  
Blood Coagulation ◽  
Clotting Factors ◽  
Sulphated Polysaccharides ◽  
Hageman Factor ◽  
Normal Plasma ◽  
Plasma Factors ◽  
Positively Charged

SummaryThe defective thromboplastin formation in Hageman factor deficient plasma is completely corrected using incubation tubes which have been coated previously with normal plasma. Positively or negatively charged molecules as protamin and sulphated polysaccharides interfere with this correction in a way that gives evidence Hageman factor is a positively charged protein.The defective thromboplastin generation of Hageman factor deficient incubation mixtures is corrected by addition of a purified Hageman factor preparation. Pre-incubation of Hageman factor with HF deficient serum improves the thromboplastin formation further, while pre-incubation of Hageman factor with HF deficient plasma abolishes this correction complete. Possibly here lies the key for the fact that serum clotting factors augment and plasma factors deteriorate during the clotting process.

scholarly journals Assessment of Hageman factor activation in human plasma: quantification of activated Hageman factor-C1 inactivator complexes by an enzyme- linked differential antibody immunosorbent assay

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 636-641
Author(s):  
AP Kaplan ◽  
B Gruber ◽  
PC Harpel
Keyword(s):  
Complex Formation ◽  
Immunosorbent Assay ◽  
Time Dependent ◽  
Enzyme Linked Immunosorbent Assay ◽  
Contact Activation ◽  
Hageman Factor ◽  
Normal Plasma ◽  
Dose Dependent Increase ◽  
Dose Dependent

An enzyme-linked immunosorbent assay has been developed for the quantitation of activated Hageman factor-C1 inactivator (HF-C1 INH) complexes. Addition of increasing quantities of either of the major forms of activated Hageman factor (HFa or HFf) to normal plasma or to Hageman factor-deficient plasma leads to a dose-dependent increase in activated HF-C1 INH complexes. As little as 0.5 micrograms/mL of activated HF added to plasma can be detected, corresponding to activation of approximately 2% of plasma HF. The sensitivity of the assay is increased at least tenfold when complexes are formed in HF- deficient plasma, indicating competition between unactivated HF and activated HF-C1 INH complexes for binding to the antibody. Specificity is demonstrated in that addition of activated HF to hereditary angioedema plasma yields less than 1% of the activated HF-C1 INH complex formation obtained with normal plasma. Kaolin activation of HF- deficient plasma yields no detectable complex formation. Kaolin activation of prekallikrein-deficient plasma demonstrates a time- dependent increase in formation of activated HF-C1 INH complex consistent with the ability of HF in this plasma to autoactivate as the time of incubation with the surface is increased. Kaolin treatment of high-molecular weight (HMW) kininogen-deficient plasma yields an even more profound abnormality in the rate of formation of activated HF-C1 INH complexes reflecting the complex role of HMW kininogen in the initiation of contact activation. Although addition of corn inhibitor to plasma prevents activated HF-C1 INH complex formation, it does not inhibit activated HF sufficiently fast to prevent prekallikrein activation.

The Prephase Accelerator. Present Status

1961 ◽  
Vol 6 (02) ◽  
pp. 254-260 ◽  
Author(s):  
F Duckert
Keyword(s):  
Present Status ◽  
Factor Ix ◽  
Quantitative Assay ◽  
Assay Method ◽  
Clotting Factors ◽  
Haemophilia B ◽  
Hageman Factor ◽  
One Stage ◽  
The One ◽  
Generation Test

SummaryThe properties of the prephase accelerator (PPA) are indicated as well as its differentiation from other known clotting factors. PPA is either a reaction product or a degratation product. For its normal formation genuine factor IX, PTA and ? Hageman factor are necessary.The one-stage quantitative assay method for factor “IX” does not determine the factor lacking in haemophilia B. This method gives a measure of PPA.Some practical observations are made concerning the value of the one-stage assay method for factor “IX” and of the thromboplastin generation test for the diagnosis of haemophilia B.

scholarly journals Assessment of Hageman factor activation in human plasma: quantification of activated Hageman factor-C1 inactivator complexes by an enzyme- linked differential antibody immunosorbent assay

Blood ◽  
1985 ◽  
Vol 66 (3) ◽  
pp. 636-641 ◽  
Author(s):  
AP Kaplan ◽  
B Gruber ◽  
PC Harpel
Keyword(s):  
Complex Formation ◽  
Immunosorbent Assay ◽  
Time Dependent ◽  
Enzyme Linked Immunosorbent Assay ◽  
Contact Activation ◽  
Hageman Factor ◽  
Normal Plasma ◽  
Dose Dependent Increase ◽  
Dose Dependent

Abstract An enzyme-linked immunosorbent assay has been developed for the quantitation of activated Hageman factor-C1 inactivator (HF-C1 INH) complexes. Addition of increasing quantities of either of the major forms of activated Hageman factor (HFa or HFf) to normal plasma or to Hageman factor-deficient plasma leads to a dose-dependent increase in activated HF-C1 INH complexes. As little as 0.5 micrograms/mL of activated HF added to plasma can be detected, corresponding to activation of approximately 2% of plasma HF. The sensitivity of the assay is increased at least tenfold when complexes are formed in HF- deficient plasma, indicating competition between unactivated HF and activated HF-C1 INH complexes for binding to the antibody. Specificity is demonstrated in that addition of activated HF to hereditary angioedema plasma yields less than 1% of the activated HF-C1 INH complex formation obtained with normal plasma. Kaolin activation of HF- deficient plasma yields no detectable complex formation. Kaolin activation of prekallikrein-deficient plasma demonstrates a time- dependent increase in formation of activated HF-C1 INH complex consistent with the ability of HF in this plasma to autoactivate as the time of incubation with the surface is increased. Kaolin treatment of high-molecular weight (HMW) kininogen-deficient plasma yields an even more profound abnormality in the rate of formation of activated HF-C1 INH complexes reflecting the complex role of HMW kininogen in the initiation of contact activation. Although addition of corn inhibitor to plasma prevents activated HF-C1 INH complex formation, it does not inhibit activated HF sufficiently fast to prevent prekallikrein activation.

Activation of cytochrome c to a peroxidase compound I-type intermediate by H2O2: relevance to redox signalling in apoptosis

2004 ◽  
Vol 71 ◽  
pp. 97-106 ◽  
Author(s):  
Mark Burkitt ◽  
Clare Jones ◽  
Andrew Lawrence ◽  
Peter Wardman
Keyword(s):  
Cytochrome C ◽  
Hydroxyl Radical ◽  
Redox Regulation ◽  
Chemotherapeutic Agents ◽  
Tyrosyl Radical ◽  
Compound I ◽  
Definitive Evidence ◽  
Enhanced Production ◽  
Physico Chemical

The release of cytochrome c from mitochondria during apoptosis results in the enhanced production of superoxide radicals, which are converted to H2O2 by Mn-superoxide dismutase. We have been concerned with the role of cytochrome c/H2O2 in the induction of oxidative stress during apoptosis. Our initial studies showed that cytochrome c is a potent catalyst of 2′,7′-dichlorofluorescin oxidation, thereby explaining the increased rate of production of the fluorophore 2′,7′-dichlorofluorescein in apoptotic cells. Although it has been speculated that the oxidizing species may be a ferryl-haem intermediate, no definitive evidence for the formation of such a species has been reported. Alternatively, it is possible that the hydroxyl radical may be generated, as seen in the reaction of certain iron chelates with H2O2. By examining the effects of radical scavengers on 2′,7′-dichlorofluorescin oxidation by cytochrome c/H2O2, together with complementary EPR studies, we have demonstrated that the hydroxyl radical is not generated. Our findings point, instead, to the formation of a peroxidase compound I species, with one oxidizing equivalent present as an oxo-ferryl haem intermediate and the other as the tyrosyl radical identified by Barr and colleagues [Barr, Gunther, Deterding, Tomer and Mason (1996) J. Biol. Chem. 271, 15498-15503]. Studies with spin traps indicated that the oxo-ferryl haem is the active oxidant. These findings provide a physico-chemical basis for the redox changes that occur during apoptosis. Excessive changes (possibly catalysed by cytochrome c) may have implications for the redox regulation of cell death, including the sensitivity of tumour cells to chemotherapeutic agents.

Differential Role of Components of the Fibrinolytic System in the Formation and Removal of Thrombus Induced by Endothelial Injury

1999 ◽  
Vol 81 (04) ◽  
pp. 601-604 ◽  
Author(s):  
Hiroyuki Matsuno ◽  
Osamu Kozawa ◽  
Masayuki Niwa ◽  
Shigeru Ueshima ◽  
Osamu Matsuo ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Thrombus Formation ◽  
Endothelial Injury ◽  
Fibrinolytic System ◽  
Tissue Type ◽  
Clot Lysis ◽  
Wild Type ◽  
Type Plasminogen Activator ◽  
Pai 1

SummaryThe role of fibrinolytic system components in thrombus formation and removal in vivo was investigated in groups of six mice deficient in urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), or plasminogen activator inhibitor-1 (PAI-1) (u-PA-/-, t-PA-/- or PAI-1-/-, respectively) or of their wild type controls (u-PA+/+, t-PA+/+ or PAI-1+/+). Thrombus was induced in the murine carotid artery by endothelial injury using the photochemical reaction between rose bengal and green light (540 nm). Blood flow was continuously monitored for 90 min on day 0 and for 20 min on days 1, 2 and 3. The times to occlusion after the initiation of endothelial injury in u-PA+/+, t-PA+/+ or PAI-1+/+ mice were 9.4 ± 1.3, 9.8 ± 1.1 or 9.7 ± 1.6 min, respectively. u-PA-/- and t-PA-/- mice were indistinguishable from controls, whereas that of PAI-1-/- mice were significantly prolonged (18.4 ± 3.7 min). Occlusion persisted for the initial 90 min observation period in 10 of 18 wild type mice and was followed by cyclic reflow and reocclusion in the remaining 8 mice. At day 1, persistent occlusion was observed in 1 wild type mouse, 8 mice had cyclic reflow and reocclusion and 9 mice had persistent reflow. At day 2, all injured arteries had persistent reflow. Persistent occlusion for 90 min on day 0 was observed in 3 u-PA-/-, in all t-PA-/- mice at day 1 and in 2 of the t-PA-/-mice at day 2 (p <0.01 versus wild type mice). Persistent patency was observed in all PAI-1-/- mice at day 1 and in 5 of the 6 u-PA-/- mice at day 2 (both p <0.05 versus wild type mice). In conclusion, t-PA increases the rate of clot lysis after endothelial injury, PAI-1 reduces the time to occlusion and delays clot lysis, whereas u-PA has little effect on thrombus formation and spontaneous lysis.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

Sign in / Sign up

Export Citation Format

Share Document