Inhibition of human activated Factor X by antithrombin III and alpha 1-proteinase inhibitor in human plasma.

Circumstantial evidence suggested that normal human plasma contained a substance regulating the neutralization of F.Xa by F.Xa inhibitor(XaI), (Yin et.al.,Adv.Exper. Med. & Biol., 52 : 239, 1975, Plenum Press, N.Y.).This plasma component has now been isolated and partially purified in our laboratory, and tentatively designated as “Anti-XaI”.In experiments employing purified components, when Anti-XaI was incubated at 37°C with F.Xa, Xal and heparin for two minutes at pH7.5, the amount of F.Xa inhibited was inversely proportional to the Anti-XaI concentration. But, when the F.Xa was replaced by thrombin in the incubation mixture, the neutralization of thrombin clotting activity was undisturbed.Anti-XaI was found to be neither PF3 nor PF4.These and other data strongly suggest that the “Antithrombin III pathway” is more complex than currently believed to be. In circulating blood an equilibrium state must exist between Anti-XaI and XaI.Under certain conditions when the Anti-XaI activity is predominant the rate of F.Xa neutralization bv XaI then becomes slower than the activation of prothrombin to thrombin by F.Xa.

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A Hitherto Undescribed Naturally Occurring Plasma Antagonist of Activated Factor X Inhibitor (Antithrombin III)

10.1055/s-0039-1684556 ◽

1979 ◽

Author(s):

E.T. Yin ◽

W.J. Salsgiver ◽

O. Tangen

Keyword(s):

Equilibrium State ◽

Human Plasma ◽

Antithrombin Iii ◽

Circumstantial Evidence ◽

Incubation Mixture ◽

Factor X ◽

Normal Human Plasma ◽

Plasma Component ◽

Naturally Occurring ◽

Normal Human

Circumstantial evidence suggested that normal human plasma contained a substance regulating the neutralization of F. Xa by F. Xa inhibitor (XaI), (Yin et.al., Adv. Exper. Med.& Biol., 52: 239, 1975, Plenum Press, N.Y.).This plasma component has now been isolated and partially purified in our laboratory, and tentatively designated as “Anti-Xal”.In experiments employing purified components, when Anti-Xal was incubated at 37°C with F. Xa. Xal and heparin for two minutes at pH7.5, the amount of F. Xa inhibited was inversely proportional to the Anti-XaI concentration. But, when the F. Xa was replaced by thrombin in the incubation mixture, the neutralization of thrombin clotting activity was undisturbed. Anti-Xa I was found to be neither PF3 nor PF6.These and other data strongly suggest that the “Antithrombin ill pathway” is more complex than currently believed to be. In circulating blood an equilibrium state must exist between Anti-Xal and Xal. Under certain conditions when the Anti-Xal activity is predominant the rate of F.Xa neutralization by Xal then becomes slower than the activation of prothrombin to thrombin by F.Xa.

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Normal human plasma contains a naturally occurring antagonist of activated factor X inhibitor (antithrombin III) activity

Thrombosis Research ◽

10.1016/0049-3848(79)90162-2 ◽

1979 ◽

Vol 15 (3-4) ◽

pp. 557-561 ◽

Cited By ~ 5

Author(s):

E.Thye Yin ◽

William J. Salsgiver ◽

Oddvar Tangen

Keyword(s):

Human Plasma ◽

Antithrombin Iii ◽

Factor X ◽

Normal Human Plasma ◽

Naturally Occurring ◽

Normal Human ◽

Antithrombin Iii Activity

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Inhibition of factor X and factor V activation by dermatan sulfate and a pentasaccharide with high affinity for antithrombin III in human plasma

European Journal of Biochemistry ◽

10.1111/j.1432-1033.1990.tb19363.x ◽

1990 ◽

Vol 193 (2) ◽

pp. 485-493 ◽

Cited By ~ 10

Author(s):

Frederick A. OFOSU ◽

Jean CHOAY ◽

Nooroldin ANVARI ◽

Lindsay M. SMITH ◽

Morris A. BLAJCHMAN

Keyword(s):

Human Plasma ◽

Antithrombin Iii ◽

Dermatan Sulfate ◽

Factor V ◽

Factor X ◽

High Affinity

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Potentially Thrombogenic Materials in Factor IX Concentrates

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647857 ◽

1975 ◽

Vol 33 (03) ◽

pp. 617-631 ◽

Cited By ~ 47

Author(s):

H. S Kingdon ◽

R. L Lundblad ◽

J. J Veltkamp ◽

D. L Aronson

Keyword(s):

Human Plasma ◽

Antithrombin Iii ◽

Factor Ix ◽

In Vitro Assays ◽

Substantial Agreement ◽

Coefficient Of Correlation

SummaryFactor IX concentrates manufactured from human plasma and intended for therapeutic infusion in man have been suspected for some time of being potentially thrombogenic. In the current studies, assays were carried out in vitro and in vivo for potentially thrombogenic materials. It was possible to rank the various materials tested according to the amount of thrombogenic material detected. For concentrates not containing heparin, there was substantial agreement between the in vivo and in vitro assays, with a coefficient of correlation of 0.77. There was no correlation between the assays for thrombogenicity and the antithrombin III content. We conclude that many presently available concentrates of Factor IX contain substantial amounts of potentially thrombogenic enzymes, and that this fact must be considered in arriving at the decision whether or not to use them therapeutically.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650592 ◽

1996 ◽

Vol 76 (03) ◽

pp. 411-416 ◽

Cited By ~ 8

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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A Chromogenic Factor X Assay With New Standardized Reagents

10.1055/s-0038-1665663 ◽

1979 ◽

Author(s):

P Friberger ◽

C Lenne

Keyword(s):

Human Plasma ◽

Suitable Method ◽

Chromogenic Substrate ◽

Factor X ◽

Normal Human Plasma ◽

Normal Plasma ◽

Normal Human

A recently published method for Factor X (FX) assay (1) utilizing Russel's Viper Venom (RVV) and a chromogenic substrate has been further investigated by testing a large number of parameters. This method has been considered as a suitable method for monitoring coumarol treatment (Bergström et al).The conditions for the activation of FX by purified preparations of the RVV have been studied as well as the conditions for FXa determination with a new chromogenic substrate Bz-Ile-Glu(γ-piperidyl)-Gly-Arg-pNA (S-2337). Both purified factors and normal plasma have been used. The effect of plasma inhibitors as well as the selectivity of the method has been studied.The reproducibility and stability of the different reagents and standards have been studied and found to be good.The amount of FXa activity obtained from normal human plasma has been titrated with FXa inhibitors of known purity.1) Aurell L. et al, Thromb. Res., 11, 595 (1977)2) Bergström et al, Thromb. Res., 12, 531 (1978)

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