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.

Coagulation Findings in Rats with Experimental Hypersplenism and Their Changes after Splenectomy and after Administration of Adrenaline

1970 ◽  
Vol 23 (03) ◽  
pp. 593-600
Author(s):  
P Pudlák ◽  
I Farská ◽  
V Brabec ◽  
V Pospíšilová
Keyword(s):  
Factor Viii ◽  
Normal Control ◽  
Normal Values ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Factor V ◽  
Thrombin Time ◽  
Factor Ii ◽  
Recalcification Time

Summary1. The following coagulation changes were found in rats with experimental hypersplenism: a mild prolongation of the recalcification time, shortened times in Quick’s test, a lowered activity in plasma thrombin time and shortened times in the partial thromboplastin test. Concentrations of factor II, V, VII (+X), VIII and X did not differ from those of normal control rats.2. The administration of adrenaline to hypersplenic rats induced the correction of the partial thromboplastin test, Quick’s test and plasma thrombin time to normal values. Concentrations of coagulation factors were not significantly changed. An increase was found in factor V.3. Splenectomy performed in hypersplenic rats was followed by a shortened recalcification time, a prolongation of the partial thromboplastin test and of the test with partial thromboplastin and kaolin. A prolongation was also observed in Quick’s test. Complete correction of plasma thrombin time was not observed. The concentration of factor VII increased.4. The administration of adrenaline to splenectomized rats with experimental hypersplenism did not induce any significant changes with the exception of a corrected plasma thrombin time and a decreased concentration of factor VIII.5. A different reaction of factor VIII to adrenaline in normal and hypersplenic rats is pointed out.

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.

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.

scholarly journals Rare Coagulation Disorders

1999 ◽  
Vol 82 (10) ◽  
pp. 1207-1214 ◽  
Author(s):  
Flora Peyvandi ◽  
P. M. Mannucci
Keyword(s):  
Hemophilia A ◽  
Clinical Manifestations ◽  
Von Willebrand Disease ◽  
Factor Vii ◽  
Factor V ◽  
Muslim Country ◽  
Factor X ◽  
Coagulation Disorders ◽  
Factor Ii ◽  
Von Willebrand

SummaryThe type of hemorrhagic manifestations that occur in patients with recessively transmitted coagulation disorders and their optimal treatment are not well established as for hemophilia A and B and von Willebrand disease, due to the rarity of these disorders. In a Muslim country like Iran where consanguineous marriages are frequent these disorders are less rare. We chose to evaluate the pattern of bleeding symptoms in 237 Iranian patients with the inherited deficiencies of fibrinogen, factor II, combined factor V and factor VIII, factor V, factor VII and factor X. Considering “severe” life-endangering hemorrhages such as those in the CNS, gastrointestinal tract and from the umbilical cord and those potentially handicapping such as hematomas and hemarthroses; and “mild” epistaxis, menorrhagia, hematuria, oral and postsurgical bleeding, it would appear the most severe diseases are factor X and factor II deficiencies. For the remaining defects only a minority of patients, even those with unmeasurable plasma levels, had life-endangering hemorrhages or muscoloskeletal disabilities as a consequence of hemarthroses and hematomas. The relatively mild severity of clinical manifestations in recessive coagulation disorders commands safety as the primary criterion in the choice of replacement material for treatment. Hence, virally inactivated plasma and factor concentrates should be the products of choice.

Rare bleeding disorders in children: towards a local registry

2021 ◽  
Author(s):  
Д.Б. Флоринский ◽  
А.В. Пшонкин ◽  
А.В. Полетаев ◽  
Д.В. Федорова ◽  
Е.А. Серегина ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Coagulation Factors ◽  
Hereditary Diseases ◽  
Factor Vii ◽  
Coagulation System ◽  
Factor V ◽  
Bleeding Disorders ◽  
Factor X ◽  
Blood Coagulation Factors ◽  
Factor Xi Deficiency

Введение. Редкие коагулопатии представляют собой гетерогенную группу наследственных заболеваний, для которых характерен количественный или качественный дефицит факторов свертывания крови. Цель исследования: проанализировать частоту встречаемости и клинические проявления редких коагулопатий у детей, определить корреляции степени тяжести клинических проявлений с активностью дефицитного фактора. Материалы и методы. На основании анализа деперсонифицированной базы данных из общего числа визитов к врачам, специализирующимся на болезнях свертывающей системы, с января 2017 г. по декабрь 2019 г. была изучена частота встречаемости редких коагулопатий. Оценивали основные локализации кровотечений и степень выраженности клинических проявлений, используя шкалу педиатрического опросника кровоточивости (англ. Pediatric Bleeding Questionnaire, PBQ). Анализ корреляции между величиной PBQ и значением активности дефицитного фактора проводили с применением метода Пирсона. Результаты. За 2017–2019 гг. в ФГБУ НМИЦ ДГОИ им. Д. Рогачева Минздрава России диагностировано 47 пациентов с редкими коагулопатиями: 14 пациентов с гипо/афибриногенемией, 21 пациент с дефицитом фактора VII, 5 пациентов с дефицитом фактора XI, 3 пациента с комбинированным дефицитом витамин К-зависимых факторов, 2 пациента с дефицитом фактора V, 1 пациент с дефицитом фактора X и 1 пациент с сочетанным дефицитом факторов V и VIII. Заключение. Распространенность той или иной редкой коагулопатии подвержена этническим особенностям населения и не всегда пропорциональна ожидаемой частоте. Требуется больше данных для установления местных особенностей распространения редких коагулопатий и выработки адекватных критериев диагностики. Background. Rare bleeding disorders are a heterogeneous group of hereditary diseases characterized by a quantitative or qualitative deficiency of blood coagulation factors. Objectives: to analyze the incidence and clinical manifestations of various rare bleeding disorders in children, to identify correlations of clinical manifestations severity with the activity of a deficient factor. Patients/Methods. According depersonalized database of the total number of visits (from January 2017 to December 2019) to doctors specializing in diseases of the coagulation system, the incidence of rare bleeding disorders was studied. The main sites of bleeding and the severity of clinical manifestations were assessed with the Pediatric Bleeding Questionnaire (PBQ) scale. Pearson method was used to analyze the correlation between the PBQ value and the deficient factor activity. Results. For years 2017–2019 at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology 47 patients with rare bleeding disorders were diagnosed, оf these, 14 patients with hypo/afibrinogenemia, 21 patients with factor VII deficiency, 5 patients with factor XI deficiency, 3 patients with combined deficiency of vitamin K-dependent factors, 2 patients with factor V deficiency, 1 patient with factor X deficiency and 1 patient with combined factors V and VIII deficiency. Conclusions. The prevalence of one or another rare bleeding disorder is vulnerable to ethnic characteristics of the population and is not always proportional to the expected frequency. More data is required to establish the local characteristics of the spread of rare bleeding disorders and to develop adequate diagnostic criteria.

Effects on Coagulation of Levonorgestrel- and Desogestrel-containing Low Dose Oral Contraceptives: a Cross-over Study

2000 ◽  
Vol 84 (07) ◽  
pp. 4-8 ◽  
Author(s):  
Joost Meijers ◽  
Abraham van den Ende ◽  
Adam van Enk ◽  
Bonno Bouma ◽  
Guido Tans ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Oral Contraceptives ◽  
Statistical Significance ◽  
Plasma Concentrations ◽  
Coagulation Factors ◽  
Factor Vii ◽  
Factor V ◽  
Factor Ii ◽  
Venous Thromboembolic ◽  
Dose Oral

SummaryCombined oral contraceptives (OC) are known to increase the risk of venous thromboembolism. The aim of this randomized, cycle-controlled, cross-over study in 28 healthy volunteers was to assess potential differences between the effects of an OC containing 150 µg levonorgestrel (as representative of the so-called second generation OC) and an OC containing 150 µg desogestrel (as representative of the third generation OC) in combination with 30 µg ethinylestradiol on several coagulation factors and markers of thrombin formation. All participants used each OC for two cycles, and were switched to the other OC after a washout period of two menstrual cycles. The plasma concentrations of factors II, VII, X, and fibrinogen significantly increased during use of both the levonorgestrel- and desogestrel-containing OC’s. The plasma concentrations of factor VIII increased, and of factor V decreased, changes which only reached statistical significance during the use of the desogestrel-containing OC. During exposure to the desogestrel-containing OC, as compared with the levonorgestrel-containing OC, both factor VII and factor II showed a greater increase (FVII: 32% and 12% respectively; p <0.0001; FII: 16% and 12% respectively; p = 0.048), whereas factor V showed a greater decrease (–11% and –3% respectively; p = 0.010). Only one of the markers for ongoing coagulation (prothrombin fragment 1+2) showed a significant increase during OC use, whereas concentrations of thrombin-antithrombin complexes and soluble fibrin remained unchanged. For these markers, there was no difference between the tested OC’s. We conclude that there are differences between the effects of levonorgestrel and desogestrel-containing OC’s on some coagulation factors. Whether these changes provide a biological explanation for the reported differences in venous thromboembolic risk is as yet unclear. The real challenge now becomes to define a pattern of changes in the various systems which, if affected simultaneously, may tip the hemostatic balance towards a prethrombotic state and may lead to overt clinical venous thromboembolism.

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.

Changes Occurring During Coagulation in Glass. I. Normal Human Blood

1960 ◽  
Vol 4 (01) ◽  
pp. 001-016
Author(s):  
Jessica H. Lewis ◽  
Paul Didisheim ◽  
John H. Ferguson ◽  
Kenichi Hattori
Keyword(s):  
Coagulation Factors ◽  
Factor Ix ◽  
Factor Vii ◽  
Sodium Oxalate ◽  
Factor V ◽  
Rapid Rise ◽  
Rapid Fall ◽  
Glass Tubes ◽  
Normal Human ◽  
The Individual

SummaryNormal whole blood was allowed to stand in glass tubes at 37° C, and the clotting process stopped at various intervals by the addition of sodium oxalate. During the first 15 minutes a marked acceleration of clotting activity was found. Study of the individual coagulation factors showed the following changes: a sustained and rapid fall in platelet count, a sustained and rapid rise in PTC (factor IX), a steady fall in fibrinogen, a more gradual fall in AHF (factor VIII), a rapid rise and subsequent fall in proaccelerin (factor V) activity, a somewhat lesser and slower rise and fall in proconvertin (factor VII) activity, and a slow fall in prothrombin concentration. No changes were noted in Hageman factor or PTA activities.

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 Studies of a mechanism inhibiting the initiation of the extrinsic pathway of coagulation

Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 645-651 ◽  
Author(s):  
LV Rao ◽  
SI Rapaport
Keyword(s):  
Tissue Factor ◽  
Factor Viia ◽  
Factor Xa ◽  
Factor Ix ◽  
Factor Vii ◽  
Factor X ◽  
Extrinsic Pathway ◽  
Mechanism Of Inhibition ◽  
Peptide Release ◽  
Release Assay

Abstract We have extended earlier studies (Blood 66:204, 1985) of a mechanism of inhibition of factor VIIa/tissue factor activity that requires a plasma component (called herein extrinsic pathway inhibitor or EPI) and factor Xa. An activated peptide release assay using 3H-factor IX as a substrate was used to evaluate inhibition. Increasing the tissue factor concentration from 20% to 40% (vol/vol) overcame the inhibitory mechanism in normal plasma but not in factor VII-deficient plasma supplemented with a low concentration of factor VII. A second wave of factor IX activation obtained by a second addition of tissue factor to plasma with a normal factor VII concentration was almost abolished by supplementing the reaction mixture with additional EPI and factor X. Factor Xa's active site was necessary for factor Xa's contribution to inhibition, but preliminary incubation of factor Xa with EPI in the absence of factor VIIa/tissue factor complex or of factor VIIa/tissue factor complex in the absence of EPI did not replace the need for the simultaneous presence of factor Xa, factor VIIa/tissue factor, calcium, and EPI in an inhibitory reaction mixture. Inhibition of factor VIIa/tissue factor was reversible; both tissue factor and factor VIIa activity could be recovered from a dissociated, inhibited factor VIIa/tissue factor complex. EPI appeared to bind to a factor VIIa/tissue factor complex formed in the presence of factor Xa but not to a factor VIIa/tissue factor complex formed in the absence of factor Xa.

Sign in / Sign up

Export Citation Format

Share Document