Coagulability of Blood and Fibrinolysis Related to Age and Lipids

1975 ◽  
Author(s):  
T. Matsuda
Keyword(s):  
Factor Viii ◽  
Antithrombin Iii ◽  
Normal Subjects ◽  
Factor Vii ◽  
Factor V ◽  
Factor X ◽  
Progressive Decline ◽  
Cholesterol Levels ◽  
Α2 Macroglobulin ◽  
Older Subjects

Levels of factor VIII, factor VII-X, factor X, factor V, fibrinogen, antithrombin III, euglobulin lysis times, plasminogen, α2-macroglobulin, α1-antitrypsin and FDP were determined in 487 healthy normal subjects from age 20 to 94. In subjects over age 60, serum lipids were determined simultaneously.In the subjects over age 60, levels of factor VIII, fibrinogen, antithrombin III, α2-maeroglobulin, α1-antitrypsin and FDP were higher, factor V activity was lower, and euglobulin lysis times were shorter than in subjects under age 50. In the older subjects, levels of factor VII-X, factor X fibrinogen, antithrombin III, plasminogen and FDP showed slight but progressive decline with age. In these subjects over age 60, serum cholesterol levels were significantly correlated with levels of factor VII-X, factor X, antithrombin III, plasminogen and FDP; antithrombin III concentration was significantly correlated with factor X activity but not with factor VII-X activity; euglobulin lysis times were correlated with obesity.

HEPARIN IS NOT AN EFFICIENT INHIBITOR OF THE FACTOR Xa-DEPENDENT ACTIVATION OF FACTOR V AND FACTOR VIII

1987 ◽  
Author(s):  
F A Ofosu ◽  
G J Modi ◽  
M R Buchanan ◽  
J Hirsh ◽  
M A Blajchman
Keyword(s):  
Factor Viii ◽  
Antithrombin Iii ◽  
Specific Inhibitor ◽  
Factor Xa ◽  
Factor V ◽  
Factor X ◽  
Inhibitory Effects ◽  
Efficient Inhibitor ◽  
System 1 ◽  
Prothrombin Activation

We have previously proposed that the steps in coagulation most sensitive to inhibition by heparin are the thrombin-dependent activation of factor V and factor VIII. This observation was based on the demonstration that therapeutic concentrations of heparin or 1μM of the thrombin specific inhibitor, phe-pro-arg CH2Cl (PPACK) completely inhibited the activation of prothrombin when contact-activated plasma (CAP) was recalcified for up to 1 min. Under similar conditions, heparin and PPACK only partially inhibited the activation of factor X. Moreover, the addition of thrombin (lOnM) to CAP 1 min before that of heparin or PPACK reversed their inhibitory effects. We now provide further support for our hypothesis by showing that when the activity of thrombin is suppressed by heparin or PPACK, efficient activation of radiolabelled prothrombin occurs only when the factor Xa then present activates factor V and factor VIII. We compared the effects of HEP of PPACK on the following four systems for initiating the activation of prothrombin: (1) CAP; (2) CAP + lOnM thrombin; (3) CAP + InM Xa and (4) unactivated plasma + InM Xa + InM Va + coagulant phospholipids. In each system, the enzymes were added 1 min before the heparin or PPACK. In the absence of heparin or PPACK, all four systems generated the same amount of thrombin activity in 45s. Complete inhibition of prothrombin activation by heparin and PPACK was observed only in system 1 which did not contain exogenous thrombin or factor Xa. No inhibition by heparin or PPACK was observed when thrombin or factor Xa was added to CAP in systems (2) and (3). Only partial inhibition was observed in system (4) which contained exogenous prothrombi-nase complex. Factor Xa thus provides an effective by-pass mechanism for the activation of factor VIII and factor V in plasma containing therapeutic concentrations of heparin. Our data provide further evidence that the heparin-antithrombin III system is not effective in inactivating factor Xa. These results support the hypothesis that in unactivated normal plasma, the primary anticoagulant effect of heparin is the inhibition of the thrombin-dependent activation of factor V and factor VIII.

COAGULATION, FIBRINOLYSIS AND PLATELET FUNCTION DURING COUMARIN THERAPY

1987 ◽  
Author(s):  
D A Taberner ◽  
J M Thomson ◽  
L Poller
Keyword(s):  
Factor Viii ◽  
Protein C ◽  
T Test ◽  
Factor Vii ◽  
Factor V ◽  
Factor X ◽  
Complex Activity ◽  
Oral Anticoagulant Treatment ◽  
Protein C Activity ◽  
Paired T Test

The inactivation of factors VIII:C, V:C and fast acting TPA inhibitor by activated Protein C indicates that oral anticoagulation is more than simple reduction of prothrombin complex activity. To investigate these changes, six patients were studied after stopping oral anticoagulant treatment. Protein C activity and C antigen, Factors VIII:C, VIII:vWFAg, V:C, V:Ag, X:C, VII:C, fibrinogen and TPA activity were measured during long-term nicoumalone therapy (duration of therapy 8-96 months, mean 28 months), and after discontinuation on days 2, 4, 8, 10, 15, 30 and 42.The INR on the last day of therapy ranged between 2.0 - 3.3, (mean 2.6). Protein C activity and antigen and factor X became normal by day 8; factor II by day 10. Factor VII activity peaked on day 8, falling to resting levels by day 30. Factor VIII parameters remained high throughout, whereas Factor V antigen showed no significant change. Factor V activity was not quantifiable untill day 8 because of non-parallelism (? PIVKA effect), but was higher on day 8 than day 42 (p < 0.002 paired “t” test) . The higher levels of factor V activity could be protein C dependent, but the high factor VIII appears unrelated. Fibrinogen levels were higher on coumarin treatment (p < 0.05 paired “t” test) and took 30 days to fall to resting level. The effect of Protein C on TPA inhibitor would be expected to increase the activity of TPA, but this activity remained unchanged. Raised fibrinogen levels did not, therefore, appear to be mediated by the effect of protein C on fibrinolysis. Fibrinogen levels in plasma influence ADP induced platelet aggregation which is known to be increased in patients receiving coumarin drugs. In conclusion, patients on coumarin treatment, in addition to showing a reduction in protein C activity, also have higher fibrinogen levels and increased platelet aggregability all of which may be undesirable.

Effect of physical exercise on blood clotting and fibrinolysis

1963 ◽  
Vol 18 (2) ◽  
pp. 337-344 ◽  
Author(s):  
Sotirios G. Iatridis ◽  
John H. Ferguson
Keyword(s):  
Blood Clotting ◽  
Normal Subjects ◽  
Factor Vii ◽  
Strenuous Exercise ◽  
Factor Xii ◽  
Factor V ◽  
Factor X ◽  
Plasma Factor ◽  
Deficient Subject ◽  
Direct Activator

The effect of strenuous exercise on the clotting and fibrinolytic systems was studied on 1 Hageman-deficient and 59 normal subjects (males aged 18–37 years). In the normal subjects there was a significant shortening of the whole-blood clotting time and of the partial thromboplastin time both in glass and in siliconized tubes. Plasma factor VIII (AHF or AHG) assays rose to 188% (average), but the specificity of the test is questioned. Factor XII (HF) increased to 318% (average) unequivocally. A postexercise increased heparin tolerance was also noted. There was no significant increase in the levels of fibrinogen, prothrombin, factor V (AcG), or factor VII (proconvertin) and factor X (Stuart). Fibrinolytic activity as measured by the euglobulin lysis and plasma plate methods increased significantly in most of the normal subjects. The data suggest that the fibrinolytic factor which increases after exercise is not active plasmin, but is related to the “activator” mechanisms. A plasma lysokinase (indirect activator) seems to preponderate in over half the cases. In 20% of cases a plasminoplastin (direct activator) may be involved. In the Hageman-deficient subject there was no improvement in clotting, and the slight changes in some of the fibrinolysis tests were nonsignificant. Submitted on October 16, 1962 Submitted on October 16, 1962

scholarly journals Activation of human factor VII by activated factors IX and X

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1143-1150 ◽  
Author(s):  
DR Masys ◽  
SP Bajaj ◽  
SI Rapaport
Keyword(s):  
Human Factors ◽  
Factor Viii ◽  
Active Site ◽  
Human Factor ◽  
Antithrombin Iii ◽  
Factor Ix ◽  
Factor Vii ◽  
Activate Factor ◽  
Factor X ◽  
Activated Factor Vii

Factor VII clotting activity increases about five-fold when blood is clotted in glass. Prior studies suggested that this results from activation induced by activated factor IX (IXa). However, in purified systems containing phospholipid and calcium, activated factor X (Xa) is known to activate factor VII rapidly. Therefore, we studied activation of factor VII by IXa and X, in systems using purified human factors. Concentrations of IXa and Xa were calculated from total activated protein concentrations rather than from active site concentrations. In the presence of phospolipid and calcium, both IXa and Xa activated factor VII 25-fold; however, Xa was roughly 800 times more efficient than IXa. Without added phospholipid, activation of factor VII by both Xa and IXa was markedly slowed, and Xa was roughly 20 times more efficient than IXa. When both phospholipid and calcium were omitted, activation of factor VII by either enzyme was negligible. Adding normal prothrombin, but not decarboxylated prothrombin, substantially slowed activation of factor VII by both Xa and IXa. Adding thrombin-activated factor VIII and antithrombin-III did not change rates of factor VII activation by either enzyme. These results from purified systems do not provide an explanation for the prior data from plasma systems.

Generation Of Coagulation Factors By The Isolated Rat Liver Perfused With A Synthetic Blood Substitute

1981 ◽  
Author(s):  
C A Owen ◽  
E J W Bowie
Keyword(s):  
Factor Viii ◽  
Rat Liver ◽  
Blood Substitute ◽  
Factor Ix ◽  
Factor Vii ◽  
Clotting Factor ◽  
Isolated Perfused Rat Liver ◽  
Factor Xii ◽  
Factor V ◽  
Factor X

Measuring the release of small amounts of a clotting factor from an isolated perfused rat liver is difficult if the perfusate already contains some of the factor. Further, platelet-containing perfusates generate a coagulant activity that may invalidate clotting assays.We have successfully employed a completely synthetic blood substitute for rat liver perfusions. The perfusate is “Fluosol-43” generously furnished by Alpha Therapeutic Corporation. The oxygen-carrying perfluorochemical is FC-43 (perfluorotributylamine) and the substitute for albumin is hydroxyethyl starch. Using the Brauer perfusion technique, we found that rat livers in 5 hours released an average of 2.3% of the normal plasma concentration of prothrombin, 8.4% factor V, 16.2% factor VII, 7.0% factor IX, 3.7% factor X, 28.3% factor XI and 12.3% factor XII. Antithrombin III and plasminogen were also generated.Only minute amounts of factor VIII were released unless serum, cryoprecipitate or cryoprecipitate-free plasma was added; then the yield was 8.8% on average. The more “venom factor” (platelet aggregability with Bothrops alternata venom) added to the synthetic perfusate, the more factor VIII was released.

scholarly journals Localization of the Inhibitory Site(s) of Pentosan Polysulphate in Blood Coagulation

1988 ◽  
Vol 60 (02) ◽  
pp. 220-225 ◽  
Author(s):  
R Wagenvoord ◽  
H Hendrix ◽  
C Soria ◽  
H C Hemker
Keyword(s):  
Factor Viii ◽  
Blood Coagulation ◽  
Antithrombin Iii ◽  
Inhibitory Effect ◽  
Independent Effect ◽  
Factor V ◽  
Factor X ◽  
Enzymatic Function ◽  
Factor Viiia ◽  
Pentosan Polysulphate

SummaryWe studied the inhibitory effect of pentosan polysulphate (PPS, Hémoclar®) on thrombin formation in blood coagulation. In contrast to a current hypothesis (1) the anti thrombin III independent effect of PPS on blood coagulation is not caused by preventing the binding of the factors IX, IXa, X, Xa, VIII, V, Va and II onto procoagulant phospholipids.We investigated the activation by thrombin of factors I, V and VIII. A strong inhibitory effect of PPS on factor VIII activation could be observed. Inhibition of the activation of factor V to the same extent requires about 30-fold higher concentrations of PPS, whereas the activation (clotting) of fibrinogen is not inhibited. The effect of PPS on factor VIIIa is two-fold: A) it inhibits its formation and B) it inhibits its function probably by the formation of a factor VIIIa-PPS complex.Prothrombinase, constituted of purified factors Xa, Va and phospholipids was not inhibited by PPS, neither were incomplete forms of this enzyme, lacking phospholipids or factor Va. The complete factor X activating enzyme (factors IXa, VIIIa and phospholipids), however, was strongly inhibited, but incomplete forms, lacking factor VIII, were not. The inhibition of the complete enzyme can be explained by reversible binding of PPS to factor VIIIa (causing an inhibition of its function) and it is not an effect on the enzymatic function of the complete enzyme. On saturation of the enzyme with an excess of factor VIIIa no inhibition by PPS is noticed.We postulate therefore that the antithrombin III independent inhibitory effect of PPS on thrombin generation on blood coagulation is by interaction with factor VIIIa. This effect is additional to the heparin-like action of PPS, i.e. potentiation of the activity of antithrombin III and/or heparin cofactor II. At concentrations attained during therapeutic use the action of pentosan polysulphate on factor VIIIa is the only one that will significantly inhibit the coagulation mechanism.

Cloning and Characterization of the Murine Coagulation Factor X Gene

2000 ◽  
Vol 83 (05) ◽  
pp. 732-735 ◽  
Author(s):  
Adrian Cooper ◽  
Zhong Liang ◽  
Francis Castellino ◽  
Elliot Rosen
Keyword(s):  
Factor Viii ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Coagulation Factor Viii ◽  
Start Codon ◽  
Factor Vii ◽  
Factor V ◽  
Factor X ◽  
Coagulation Factor Vii ◽  
Coagulation Factor V

SummaryThe gene encoding murine coagulation factor X (fX) was isolated and characterized from a λFIX II library generated from murine genomic DNA. The 20130 bp sequence contains 18049 nucleotides that extend from the initiating methionine to the polyadenylation site. 1056 nucleotides 5’ of the start codon were determined and contain putative start sites for the FX mRNA as well as sites for binding of putative transcription factors. The sequence extends 1024 3’ of the polyadenylattion site.The gene contains 8 exons and 7 introns which were determined by comparing the mouse FX cDNA and gene sequences. The exonic structure of the gene is similar to that of the other mammalian vitamin K-dependent serine proteases of the coagulation system. These include an exon encoding the prepropepetide, the gladomain, a short helical stack, two exons for the two EGF domains, the activation pepetide, and two exons encoding the serine protease domain. The 5’ sequence of the mouse FX gene overlaps with the 3’ region of the FVII gene indicating that the murine FVII and FX gene are arranged in a head to tail arrangement as they are in humans. Abbreviations: fVII, coagulation factor VII; fIX, coagulation factor IX; fX, coagulation factor X; PC, Protein C; fV, coagulation factor V; fVa, activated coagulation factor V; fVIII, coagulation factor VIII; fVIIIa, activated coagulation factor VIII.

scholarly journals Activation of human factor VII by activated factors IX and X

Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1143-1150 ◽  
Author(s):  
DR Masys ◽  
SP Bajaj ◽  
SI Rapaport
Keyword(s):  
Human Factors ◽  
Factor Viii ◽  
Active Site ◽  
Human Factor ◽  
Antithrombin Iii ◽  
Factor Ix ◽  
Factor Vii ◽  
Activate Factor ◽  
Factor X ◽  
Activated Factor Vii

Abstract Factor VII clotting activity increases about five-fold when blood is clotted in glass. Prior studies suggested that this results from activation induced by activated factor IX (IXa). However, in purified systems containing phospholipid and calcium, activated factor X (Xa) is known to activate factor VII rapidly. Therefore, we studied activation of factor VII by IXa and X, in systems using purified human factors. Concentrations of IXa and Xa were calculated from total activated protein concentrations rather than from active site concentrations. In the presence of phospolipid and calcium, both IXa and Xa activated factor VII 25-fold; however, Xa was roughly 800 times more efficient than IXa. Without added phospholipid, activation of factor VII by both Xa and IXa was markedly slowed, and Xa was roughly 20 times more efficient than IXa. When both phospholipid and calcium were omitted, activation of factor VII by either enzyme was negligible. Adding normal prothrombin, but not decarboxylated prothrombin, substantially slowed activation of factor VII by both Xa and IXa. Adding thrombin-activated factor VIII and antithrombin-III did not change rates of factor VII activation by either enzyme. These results from purified systems do not provide an explanation for the prior data from plasma systems.

Self-Damping Mechanism in Blood Coagulation

1974 ◽  
Vol 32 (01) ◽  
pp. 057-064 ◽  
Author(s):  
Y Nemerson ◽  
S.A Silverberg ◽  
J Jesty
Keyword(s):  
Tissue Factor ◽  
Blood Coagulation ◽  
Calcium Ions ◽  
Control Mechanism ◽  
Factor Vii ◽  
Damping Factor ◽  
Factor V ◽  
Factor X ◽  
Extrinsic Pathway ◽  
Two Systems

SummaryTwo reactions of the extrinsic pathway of coagulation, the activations of Factor X and prothrombin, have been studied in purified systems and shown to be self-damping. Factor X was activated by the tissue factor - Factor VII complex, and prothrombin by two systems: the coagulant protein of Taipan venom, and the physiological complex of activated Factor X, Factor V, lipid, and calcium ions. In each case the yield of enzyme, activated Factor X or thrombin, is a function of the concentration of activator. These and other observations are considered as a basis for a control mechanism in coagulation.

Haemostatic Parameters and Lifestyle Factors in Elderly Men in Italy and The Netherlands

1996 ◽  
Vol 76 (03) ◽  
pp. 411-416 ◽  
Author(s):  
Fransje C H Bijnen ◽  
Edith J M Feskens ◽  
Simona Giampaoli ◽  
Alessandro Menotti ◽  
Flaminio Fidanza ◽  
...  
Keyword(s):  
Alcohol Use ◽  
The Netherlands ◽  
Antithrombin Iii ◽  
Lifestyle Factors ◽  
Activated Partial Thromboplastin Time ◽  
Factor Vii ◽  
Fat Intake ◽  
Factor X ◽  
Elderly Men ◽  
History Of

SummaryThe association between plasma fibrinogen, factor VII, factor X, activated partial thromboplastin time, antithrombin III and the lifestyle factors cigarette smoking, alcohol use, fat intake and physical activity was assessed in 802 men aged 70-90 years in Zutphen (The Netherlands), Montegiorgio and Crevalcore (Italy).Smoking was positively associated with fibrinogen, also after adjustment for other lifestyle factors, age, use of anticoagulants and aspirin like drugs, body mass index, and history of myocardial infarction. Alcohol use was associated with increased levels of factor X and decreased levels of antithrombin III. Fat intake was positively associated with antithrombin III. Between cohorts, considerable differences were observed in levels of haemostatic parameters and the lifestyle factors. Compared to the mediterranean cohorts the Zutphen cohort showed the highest levels of fibrinogen and factor VII. Differences in lifestyle factors could, however, not explain differences between cohorts in levels of any of the haemostatic parameters, despite the observed associations between lifestyle factors and haemostatic parameters.

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