The Influence of the Thyroid Function on the Metabolic Rate of Prothrombin, Factor VII, and Factor X in the Rat

1976 ◽  
Vol 35 (03) ◽  
pp. 607-619 ◽  
Author(s):  
Allan T. van Oosterom ◽  
Herman Mattie ◽  
Wim Th Hermens ◽  
Jan J. Veltkamp
Keyword(s):  
Metabolic Rate ◽  
Thyroid Function ◽  
Coagulation Factors ◽  
Biologically Active ◽  
Factor Vii ◽  
Synthesis Rate ◽  
Apparent Difference ◽  
Vitamin K1 ◽  
Factor X ◽  
Significant Difference

SummaryThe influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and X was studied in the rat. Disappearance rates of the three coagulation factors were measured after synthesis had been blocked with appropriate doses of warfarin, and reappearance rates were assessed upon induction of synthesis by high doses of vitamin K1 injected into rats displaying coumarin induced hypocoagulability.No statistically significant difference in the disappearance and production rates of any of the factors could be found between normal euthyroid rats and thyroxin-treated hypothyroid rats proven to be euthyroid. The differences between the two euthyroid groups and the hypothyroid group were highly significant, however: hypothyroidism results in an approximately 50% decrease of the metabolic rates of the three coagulation factors under study.The reappearance of the three factors, under euthyroid as well as hypothyroid conditions, showed a biphasic pattern: in the first two hours after vitamin K1 administration to warfarin treated rats, a rapid reappearance was observed, to the same extent for all three factors, in hypo- as well as euthyroid rats. This finding suggests that in vitamin K1 deficiency an intracellular accumulation of precursor proteins (PIVKAs) occurs, which after rapid conversion into biologically active coagulation factors by vitamin K1 are shed into circulation.The subsequent phase of reappearance is much slower and reflects the synthesis rate of coagulation enzymes. It is characteristic for each factor and clearly slower in hypothyroid rats than in euthyroid rats. From this an influence of thyroid function on the synthesis rate of the protein moiety of coagulation factors can be inferred.An apparent difference between disappearance and reappearance rate of the coagulation factors in the plasma, particularly pronounced for factors VII and X in euthyroid rats, could theoretically be explained as the consequence of the model used for derivation of these rates.

scholarly journals Evidence for the presence of tissue factor activity on subendothelium

Blood ◽  
1989 ◽  
Vol 73 (4) ◽  
pp. 968-975
Author(s):  
HJ Weiss ◽  
VT Turitto ◽  
HR Baumgartner ◽  
Y Nemerson ◽  
T Hoffmann
Keyword(s):  
Tissue Factor ◽  
Umbilical Artery ◽  
Factor Viia ◽  
Rabbit Aorta ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Factor X ◽  
Factor Activity ◽  
Fibrin Deposition ◽  
Tissue Factor Activity

By a variety of methods, tissue factor activity was demonstrated in the subendothelium of rabbit aorta and human umbilical artery. In one method, everted segments of de-endothelialized vessels were mounted in an annular perfusion chamber and the subendothelial surface was exposed to nonanticoagulated human blood under controlled flow. Procoagulant activity was assessed by measuring fibrin deposition on subendothelium and fibrinopeptide A (FPA) levels in post chamber blood. Both fibrin deposition and FPA were decreased with rabbit vessel segments exposed (at a shear rate of 650 seconds-1) to blood from patients with factor VII deficiency and with umbilical artery segments (at shear rates of 90 to 180 seconds-1) that had been pretreated with a monoclonal antibody to human tissue factor. In a second method, everted umbilical artery segments were mounted on a stir bar and the subendothelial surface was exposed, with stirring, to plasma or purified coagulation factors. The capacity of the surface to clot plasma on addition of calcium was inhibited by the antibody to tissue factor. The surface also activated purified 3H-factor X in the presence of factor VIIa, but not in its absence, and this surface property was almost entirely eliminated by pretreating the vessel segments with antitissue factor. Tissue factor activity in subendothelium could play a role in both the arrest of bleeding and in promoting the formation of thrombi at sites of vascular injury.

scholarly journals Reduction of salivary tissue factor (thromboplastin) activity by warfarin therapy

Blood ◽  
1979 ◽  
Vol 53 (3) ◽  
pp. 366-374 ◽  
Author(s):  
LR Zacharski ◽  
R Rosenstein
Keyword(s):  
Tissue Factor ◽  
Vitamin K ◽  
Coagulation Factors ◽  
Human Saliva ◽  
Factor Vii ◽  
Clotting Factor ◽  
Activate Factor ◽  
Total Protein Content ◽  
Factor X ◽  
Clotting Factors

Abstract The coagulant of normal human saliva has been identified as tissue factor (thromboplastin, TF) by virtue of its ability to cause rapid coagulation in plasmas deficient in first-stage coagulation factors and to activate factor x in the presence of factor VII and by virtue of the fact that its activity is expressed only in the presence of factor VII and is inhibited by an antibody to TF. The TF is related to cells and cell fragments in saliva. Salivary TF activity has been found to be significantly reduced in patients taking warfarin. The decline in TF activity during induction of warfarin anticoagulation occurs during the warfarin-induced decline in vitamin-K-dependent clotting factor activity, as judged by the prothrombin time. The decrease in TF activity is not related to a reduction in salivary cell count or total protein content or to a direct effect of warfarin on the assay. It is hypothesized that the mechanism by which warfarin inhibits TF activity may be related to the mechanism by which it inhibits expression of the activity of the vitamin-K-dependent clotting factors. Inhibition of the TF activity may be involved in the antithrombotic effect of warfarin.

FACTOR II ACTIVATING ACTIVITY IN EXTRACTS OF TUMORAL NECROSIS FROM TWO MURINE BREAST ADENOCARCINOMAS

1987 ◽  
Author(s):  
A Blanco ◽  
R Bonfil ◽  
O Bustoabad ◽  
M Lazzari
Keyword(s):  
Coagulation Factors ◽  
Factor Vii ◽  
Factor V ◽  
Factor X ◽  
Extrinsic Pathway ◽  
Factor Ii ◽  
Metastatic Capacity ◽  
Plasma Recalcification Time ◽  
Recalcification Time ◽  
Breast Adenocarcinomas

Increased deposition and lysis of fibrin, associated with malignant tissue, has led to look for activators of both the coagulation and fibrinolytic systems produced by tumor cells. We report the evidences of a procoagblant activity (PA) in the extracts of intratumoral necrosis from two experimental breast adenocarcinomas in murine model (BALB/c). The tumors have different metastatic capacity (MC). M3 without MC and MM3 with high MC.The addition of the extracts to: 1- Normal Plasma, 2- Deficient substrates in coagulation factors, 3- Purified, fibrinogen (I), showed: 1- Shortening of the plasma recalcification time (PRT) and APTT, without ;modification on prothrombin time (PT), 2- Reduction of the PRT on deficient substrates in factors: VIII; VII; VII and X; V; V, VII and X; without modification on II deficient substrate, 3- No PA on I. Table:C: Control, s: seconds, m: minutes. The PA was not affected by heparin. The results suggest that the PA is independent of the presence of either factor VIII or factor VII (intrinsic or extrinsic pathway respectively), as well as presence of either factor V or factor X. Any effect was observed either on factor II deficient substrate or on I, so, there was no evidence of thrombin activity The PA could be act directly on factor II, suggesting that fibrin formation could be induced by a “non-classical” activation pathway. No significant differences (p>0.5) in PA were observed between both tumoral necrosis extracts. The necrotic area in M3 (37%) is bigger than in MM3 (18%). So, much more PA could be present in MM3 and this could play a role in the MC of this tumor.

scholarly journals Linkage analysis for three coagulation factors clustering on chromosome 13q34: factor VII, factor X and protein Z

2007 ◽  
Vol 5 (6) ◽  
pp. 1325-1326 ◽  
Author(s):  
C. Y. VOSSEN ◽  
S. J. HASSTEDT ◽  
C. DEMERS ◽  
F. R. ROSENDAAL ◽  
E. G. BOVILL
Keyword(s):  
Linkage Analysis ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Factor X ◽  
Protein Z

scholarly journals Reduction of salivary tissue factor (thromboplastin) activity by warfarin therapy

Blood ◽  
1979 ◽  
Vol 53 (3) ◽  
pp. 366-374 ◽  
Author(s):  
LR Zacharski ◽  
R Rosenstein
Keyword(s):  
Tissue Factor ◽  
Vitamin K ◽  
Coagulation Factors ◽  
Human Saliva ◽  
Factor Vii ◽  
Clotting Factor ◽  
Activate Factor ◽  
Total Protein Content ◽  
Factor X ◽  
Clotting Factors

The coagulant of normal human saliva has been identified as tissue factor (thromboplastin, TF) by virtue of its ability to cause rapid coagulation in plasmas deficient in first-stage coagulation factors and to activate factor x in the presence of factor VII and by virtue of the fact that its activity is expressed only in the presence of factor VII and is inhibited by an antibody to TF. The TF is related to cells and cell fragments in saliva. Salivary TF activity has been found to be significantly reduced in patients taking warfarin. The decline in TF activity during induction of warfarin anticoagulation occurs during the warfarin-induced decline in vitamin-K-dependent clotting factor activity, as judged by the prothrombin time. The decrease in TF activity is not related to a reduction in salivary cell count or total protein content or to a direct effect of warfarin on the assay. It is hypothesized that the mechanism by which warfarin inhibits TF activity may be related to the mechanism by which it inhibits expression of the activity of the vitamin-K-dependent clotting factors. Inhibition of the TF activity may be involved in the antithrombotic effect of warfarin.

Cold Promoted Activation of Factor VII

1972 ◽  
Vol 28 (02) ◽  
pp. 194-205 ◽  
Author(s):  
H Gjønnæss
Keyword(s):  
Intrinsic Factor ◽  
Coagulation Factors ◽  
The Other ◽  
Factor Vii ◽  
Factor Xii ◽  
Factor X ◽  
Reaction Sequence ◽  
Activated Factor Vii ◽  
Control Plasma

SummaryThe cold promoted shortening of the thrombotest times induced by incubation of plasma with prekallikrein activators for 20 hours at 0° C is due to activation of factor VII. No change was recorded for the other coagulation factors. The activation was strong, as the presence of 1 per cent cold activated factor VII reduced the thrombotest time of factor VII deficient plasma from 115 to 38.7 seconds.The activation of factor X by the cold activated factor VII occurred in the course of seconds, in the presence of calcium and thromboplastin. Cold promoted activation of factor VII also implied reduced cephalin time, probably via traces of thrombin inducing intrinsic factor X activator activity during the clotting test.Generation of cold promoted activator activity (CPA) was independent of coagulation factors V, VIII, IX, X, XI, and calcium, but factor XII was a prerequisite. Of factor VII even traces were sufficient for the generation of CPA. The activation of the kallikrein system, that occurs in parallel with the cold promoted activation of factor VII, occurred both in factor VII deficient plasma and in ordinary control plasma. In the reaction sequence, the activation of factor VII therefore is less likely to be the first step, it possibly is a result of activation of the kallikrein system.

Behaviour of Factors II, VII, IX, and X during Long-Term Treatment with Coumarin

1963 ◽  
Vol 09 (01) ◽  
pp. 074-089 ◽  
Author(s):  
E. A Loeliger ◽  
B van der Esch ◽  
M. J Mattern ◽  
A. S. A den Brabander
Keyword(s):  
Prothrombin Time ◽  
Coagulation Factors ◽  
Term Treatment ◽  
Factor Ix ◽  
Separate Determination ◽  
Factor X ◽  
Warfarin Sodium ◽  
Long Term Treatment ◽  
Significant Difference

SummaryDuring long-term treatment with the long-acting coumarin derivative phenprocoumarol (marcoumar) no statistically significant difference in the depression of the activity of coagulation factors II, VII, IX, and X was found. The shorter-acting anticoagulants acenocoumarol (sintrom), warfarin sodium (coumadin), and dicoumarol, possibly lower factor IX somewhat less and factor X somewhat more than they do factors II and VII.A 2.5-fold prolongation of the “prothrombin” time (using Owren 5 s human brain thromboplastin) and the same prolongation of the thrombotest time appear to correspond with a depression of all four factors from 100% down to approximately 20’%, the normal standard being a mixed population with a mean age of 29 years.Separate determination of one of the four coagulation factors concerned is pointless; “prothrombin” time estimation, and more specifically thrombotest, still remain the most reliable methods for controlling the anti-vitamin K action of anticoagulants during long-term treatment.

scholarly journals Evidence for the presence of tissue factor activity on subendothelium

Blood ◽  
1989 ◽  
Vol 73 (4) ◽  
pp. 968-975 ◽  
Author(s):  
HJ Weiss ◽  
VT Turitto ◽  
HR Baumgartner ◽  
Y Nemerson ◽  
T Hoffmann
Keyword(s):  
Tissue Factor ◽  
Umbilical Artery ◽  
Factor Viia ◽  
Rabbit Aorta ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Factor X ◽  
Factor Activity ◽  
Fibrin Deposition ◽  
Tissue Factor Activity

Abstract By a variety of methods, tissue factor activity was demonstrated in the subendothelium of rabbit aorta and human umbilical artery. In one method, everted segments of de-endothelialized vessels were mounted in an annular perfusion chamber and the subendothelial surface was exposed to nonanticoagulated human blood under controlled flow. Procoagulant activity was assessed by measuring fibrin deposition on subendothelium and fibrinopeptide A (FPA) levels in post chamber blood. Both fibrin deposition and FPA were decreased with rabbit vessel segments exposed (at a shear rate of 650 seconds-1) to blood from patients with factor VII deficiency and with umbilical artery segments (at shear rates of 90 to 180 seconds-1) that had been pretreated with a monoclonal antibody to human tissue factor. In a second method, everted umbilical artery segments were mounted on a stir bar and the subendothelial surface was exposed, with stirring, to plasma or purified coagulation factors. The capacity of the surface to clot plasma on addition of calcium was inhibited by the antibody to tissue factor. The surface also activated purified 3H-factor X in the presence of factor VIIa, but not in its absence, and this surface property was almost entirely eliminated by pretreating the vessel segments with antitissue factor. Tissue factor activity in subendothelium could play a role in both the arrest of bleeding and in promoting the formation of thrombi at sites of vascular injury.

Hemostatic risk factors in ischemic stroke

2003 ◽  
Vol 90 (12) ◽  
pp. 1094-1099 ◽  
Author(s):  
Daniela Berger ◽  
Heinrich Mattle ◽  
Bernhard Lämmle ◽  
Walter Wuillemin ◽  
Franziska Demarmels Biasiutti
Keyword(s):  
Ischemic Stroke ◽  
Relative Risk ◽  
Arterial Hypertension ◽  
Smoking Habit ◽  
Coagulation Factors ◽  
High Plasma ◽  
Factor Vii ◽  
Factor V ◽  
Factor X ◽  
Factor Ii

SummaryThe role played by hemostasis in the pathogenesis of ischemic stroke is still controversial. In the present study, we looked for a possible association of ischemic stroke and high clotting activity of factor II (FII:C), factor V (FV:C), factor VII (FVII:C), factor X (FX:C) and fibrinogen. We investigated 157 non-anti-coagulated patients (86 males, 71 females; median age 41 y, range 16-73 ), who had survived ischemic stroke for at least 2 months, and 193 healthy controls with similar age and sex distribution (104 males, 89 females; median age 39 y, range 19-74). Patients showed significantly higher body mass index, as well as significantly higher prevalence of arterial hypertension, smoking and hyperlipidemia. FV:C (p = 0.05), FX:C (p = 0.04) and fibrinogen (p = 0.05) were higher in patients as compared to controls. In a univariate risk analysis FX:C and FV:C were associated with the relative risk for ischemic stroke showing an odds ratio (OR) of up to 2.8 (95% CI: 1.05-7.6) and 3.4 (95%CI: 1.4-7.9), respectively, for levels above 130%. In a multivariate analysis using a logistic regression model including age, sex, arterial hypertension, smoking habit, diabetes, hyperlipidemia, BMI and the coagulation factors, FV:C was still found to significantly (p=0.03) add to the risk of ischemic stroke. An increase of factor FV:C by 10% was associated with an increase in the relative risk of 19% (95% CI.: 2%-38%). In conclusion, we found a high plasma level of FV:C to be a prevalent (FV:C > 130% in 20/157 patients) and independent risk factor for ischemic stroke.

Extrinsic Activation of Human Coagulation Factors IX and X on the Endothelial Surface

1991 ◽  
Vol 66 (03) ◽  
pp. 283-291 ◽  
Author(s):  
Victor J J Bom ◽  
Victor W M van Hinsbergh ◽  
Hanneke H Reinalda-Poot ◽  
Ramon W Mohanlal ◽  
Rogier M Bertina
Keyword(s):  
Tissue Factor ◽  
Factor Viia ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Factor Ix ◽  
Factor Vii ◽  
Lag Phase ◽  
Factor X ◽  
Free System ◽  
Endothelial Surface

SummaryIn previous kinetic studies, the catalytic efficiency of the activation of human coagulation factors IX and X by factor VIIa in the presence of purified tissue factor apoprotein was found to be essentially equal. These activation reactions were now studied on the surface of human umbilical vein endothelial cells. The cells were stimulated with endotoxin to express tissue factor. This tissue factor activity was saturable with factor VIIa and could be inhibited by rabbit antibodies against human tissue factor apoprotein. Only stimulated cells supported factor VIIa activity. No difference in the reactivity of factor VII and VIIa was observed in the presence of factor X, due to rapid feedback activation of factor VII by factor Xa. However, the activation of factor IX by factor VII shows a 10 min lag-phase, which reflects that the activation of factor VII by factor IXa is a less efficient process. The kinetic parameters for the factor VIIa dependent activation of factor IX and factor X on the endothelial surface were: Km 0.09 εM, Vmax 0.13 pmol/min, and Km 0.071 εM, Vmax 0.41 pmol/min, respectively. The same ratio between the Vmax for factor X and factor IX activation was observed as in a cell free system. However, the Km of factor IX was 4-fold higher on the endothelial surface than in the cell free system. Together, these kinetic parameters will favour factor X activation 5-fold over factor IX activation at physiological concentrations of these proteins.The activation of factor X by factor VIIa on the endothelial surface was characterized by a short lag-phase, which was absent in factor IX activation. Further, both the activation of factor X and factor IX were down regulated by factor Xa.

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