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At least 775 records · Page 43Linked to original sources
PubMed1975

Factor X Friuli: An immunological study in plasma and in serum using several methods.

An immunological study of factor X Friuli was carried out using an anti-human-factor X antiserum. The results obtained with different methods were compared. Only an ill-defined factor X band or precipitate was evident on standard immuno-electrophoresis and on immunodiffusion. Using a non-absorbed antiserum a precipitate was evident on eletroimmunoassay, in normal, factor X Friuli and in factor X deficient plasma. On the contary, using an antiserum which had been previously absorbed with factor X deficient plasma, a precipitate was evident only with factor X Friuli plasma or normal plasma. Excellent results were obtained with the cross-over electrophoresis. Using this method a major or factor X band was evident in normal plasma, factor II,P FACTOR VII, factor IX deficient plasmas and in the factor X FRIULI PLASMA. No factor X band was evident in factor X deficient plasmas and in absorbed normal plasma. Lighter, more cathodic bands were seen in all plasmas. These were due to secondary activities of the antiserum and could be disregarded. Friuli serum factor X and normal serum factor X showed a slightly more anodic migration as compared to their plasma counterparts. In coumarin plasma two factor X bands were evident; one normal in position and one slightly more catholidic. In the bidimensional immunoelectrophoresis two precipitates are visible in normal plasma and in factor X Friuli plasma. In factor X deficient plasma only one precipitate is evident. This latter precipitate is due to the secondary activity of the antiserum used. On the basis of these data it is concluded that factor X Friuli behaves, immunologically, as normal factor X.

Blood Coagulation Disorders↗
PubMed1985

Regulation of monocyte procoagulant by chemoattractants.

Various n-formylated peptides function as receptor-specific chemoattractants for both granulocytes and monocytes. Because these agents are important tools in the study of leukocyte function in vitro, we chose to examine their effects on leukocyte procoagulant activity. The synthetic chemotactic peptide N-formyl-methionyl-leucyl phenylalanine (FMLP) induces a fourfold increase in procoagulant activity (PCA) in cultured human monocytes at an optimal dose of 5 X 10(-9) mol/L, whereas higher doses inhibit PCA response. Although nonadherent lymphocytes are not absolutely required for PCA expression, their presence significantly amplifies monocyte PCA. Irradiation of nonadherent lymphocytes before mixing them with FMLP and adherent cells abolishes their ability to amplify PCA. Kinetic studies demonstrate an increase in optimal dose FMLP-stimulated PCA over time whereas high-dose inhibition of PCA generation occurs at various incubation times. Cell viability is unaffected by inhibitory concentrations of FMLP. Supernates from high-dose FMLP-stimulated cells fail to inhibit later expression of PCA by cells exposed to endotoxin. The cellular procoagulant remains cell-bound and exhibits characteristics of thromboplastin (tissue factor), including inhibition by concanavalin A and phospholipase C as well as the ability to shorten the clotting times of factor VIII but not factor VII-deficient substrate plasmas. These results suggest a complex system of lymphoid cell regulation of procoagulant generation by monocytes exposed to various chemotactic peptides in vitro.

Blood Coagulation↗
PubMed1994

Genetic determinants of arterial thrombosis.

This chapter describes examples of genetic variation determining plasma levels of three independent risk factors for arterial thrombotic disease, namely fibrinogen, coagulation factor VII and plasminogen activator inhibitor type 1, together with a discussion of the underlying molecular mechanisms. In each case, the data suggest that there is interaction between genotype and environment in determination of the relevant plasma level, providing a possible explanation for the differential response of different individuals to their environment.

Afibrinogenemia↗
PubMed2001

Gene targeting in hemostasis. tissue factor pathway inhibitor.

Tissue Factor Pathway Inhibitor (TFPI) is a serine protease inhibitor of the Factor VIIa/Tissue Factor (FVIIa/TF)-initiated clotting cascade. Mice expressing a mutant form of TFPI, in which its Kunitz-1 domain has been deleted (TFPIKu1delta/delta), die prematurely in embryogenesis between E9.5dpc and birth. These results provide a rationale for the absence of TFPI-deficient patients. This early mortality can be ameliorated by an accompanying heterozygous or homozygous deficiency in FVII. Thus, diminishment of FVII activity precludes the requirement for TFPI-mediated inhibition of the FVIIa/TF pathway during embryogenesis.

Animals↗
PubMed1989

The relative importance of the factors II, VII, IX and X for the prothrombinase activity in plasma of orally anticoagulated patients.

The individual importance of each of the four vitamin K-dependent clotting factors on the generation of prothrombinase activity in the plasma of orally anticoagulated patients has been investigated. Addition of purified factors VII, IX or X to plasma from deeply anticoagulated patients (International Normalized Ratio 2.8-4.8) did not influence the amount of prothrombinase activity or the amount of thrombin formed. Only the prothrombin level in the plasma determines the course of thrombin generation. Addition of increasing amounts of purified factor II, VII, IX or X to plasmas deficient in respectively factor II, VII, IX or X showed that the prothrombinase activity increases linearly with the concentration of factor II added and that the concentration below which the factors VII, IX and X start to have a measurable effect on prothrombinase activity are 5%, 20%, and 30%, respectively. Half maximal prothrombinase activity was found at about 1% factor VII, 5% factor IX and 8% factor X respectively. From these observations we conclude that primarily the variation in factor II level determines thrombin generation and hence presumably the antithrombotic effect of oral anticoagulant therapy. It therefore seems likely that, for the control of oral anticoagulant therapy, tests that reflect factor II activity would be suitable.

Administration, Oral↗
PubMed2004

The P303T mutation in the human factor VII (FVII) gene alters the conformational state of the enzyme and causes a severe functional deficiency.

We report the results of in vitro expression and biochemical characterization of the naturally occurring type II mutation Pro303Thr (P303T) in the factor VII (FVII) gene. Recombinant activated mutated FVII (FVIIa303T), compared with the activated wild-type FVII (FVIIaWT), showed reduced amidase activity toward synthetic substrates, especially when the observed reduced binding affinity for human soluble tissue factor (TF) (K(d) from 4.4 nmol/l for FVIIaWT to 17.3 nmol/l for FVIIa303T) was overcome by a fully saturating TF concentration. Likewise, factor X (FX) hydrolysis by FVIIa303T showed a reduced activity in the absence (and more severely in the presence) of TF (k(cat)/K(m) from 2.3 x 10(7)/mol/l s for FVIIaWT to 8.7 x 10(5)/mol/l s for FVIIa303T). These results showed that the mutant FVIIa is more shifted toward a zymogen-like form compared to FVIIaWT, suggesting that P303 facilitates the conformational transitions that stabilize the active form of FVIIa. The alteration of these allosteric equilibria is especially evident in the presence of TF, which was unable to shift the equilibrium toward a fully active FVIIa form. Additional experiments showed that both TF-catalysed FVII303T autoactivation and FVII303T activation by activated FX in the presence of TF were severely impaired, mainly because of an increase of the K(m) value. Altogether, these defects may explain the severe bleeding symptoms in a patient carrying the FVIIP303T mutation.

Adult↗
PubMed1994

High-dose glucocorticosteroids increase the procoagulant effects of OKT3.

The use of OKT3 as prophylaxis in renal transplantation carries an increased risk of intragraft thrombosis, which is related to the systemic activation of the coagulation system that consistently occurs after the first dose of OKT3. As only a few patients develop thrombosis after OKT3 therapy, we searched for possible additional risk factor by comparing the demographic and clinical parameters of the 13 patients who developed thrombosis in our institution to those of 218 patients who did not. Multivariate analysis showed a relationship between the dose of methylprednisolone (mPDS) given before the first OKT3 injection and the risk of thrombosis: 6 out of 42 patients (14%) who received high (30 mg/kg) mPDS experienced a thrombotic event, as compared to 7 out of the 189 patients (3.7%) who received < or = 8 mg/kg of mPDS (P < 0.01). This led us to study the effects of mPDS on the procoagulant activity induced by OKT3 on peripheral blood mononuclear cells (PBMC) in vitro. The procoagulant activity of unstimulated PBMC (mean +/- SEM: 0.6 +/- 0.1 mU/ml) reached 3.0 +/- 0.7 mU/ml after OKT3 stimulation (P = 0.0062) and further increased to 7.4 +/- 2.0 mU/ml when PBMC were first preincubated overnight with mPDS before OKT3 stimulation (P = 0.018 as compared to OKT3 alone). This process involved the tissue factor/factor VII pathway, as shown by increased membrane expression of tissue factor on monocytes as well as by a marked reduction of the induced procoagulant activity when the clotting assay was performed with factor VII-deficient plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

An enzyme immunoassay (ELISA) for the quantitation of human factor VII.

A new solid phase enzyme-linked immunosorbent assay (ELISA) was developed for the quantitation of human Factor VII antigen (F VII Ag), using a monospecific rabbit anti-F VII antiserum. Anti-F VII F(ab')2 fragments were adsorbed to polystyrene plates. The binding of serial dilutions of control or test plasma, containing F VII, was detected by incubation with peroxidase-labeled anti- FV II IgG followed by the addition of hydrogen peroxyde and O-phenylenediamine. This ELISA is specific, sensitive (detection limit: 0.05%) and accurate (coefficient of variation: 1.5-4% for within- and 1.6-9% for between-assays). F VII coagulant activity (F VII C) and F VII C) and F VII Ag were determined in large populations of controls and patients. In normal plasma (n = 38), F VII Ag ranged from 83 to 117% and the correlation coefficient between F VII Ag and F VII C was 0.94. In patients with severe (F VII C inf. 1%) congenital F VII deficiency (n = 5), F VII Ag was undetectable in two cases (inf. 0.05%) and markedly reduced (0.35 to 5.6%) in the three other cases. In patients with liver cirrhosis (n = 15), F VII Ag ranged from 21% to 59% and was in good correlation with F VII C (r = 0.84). In dicoumarol treated patients (n = 15), the levels of F VII Ag ranged from 51% to 79% and a poor correlation (r = 0.52) with F VII C was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Specificity↗
PubMed1985

Characterisation of rat tumour cell hybrids: procoagulant and fibrinolytic activities.

The formation of lung colonies after i.v. injection of highly metastatic rat mammary adenocarcinoma cells (MAT 13762) was greatly reduced by concurrent treatment of rats with heparin. The procoagulant activity (PCA) of these cells, and of a non-metastatic adenocarcinoma (DMBA-8) has therefore been measured. These have been compared with PCA expressed by MAT 13762 cell derivatives including a non-metastatic hybrid clone (MAT 13762 X DMBA-8), its metastatic revertant, and clones selected in vivo from lung metastases. Potent PCA was expressed on intact MAT 13762 cells and in their spent culture media, the latter being sedimentable and associated with shed membrane vesicles. Cell-derived PCA, unlike thromboplastin, was equally effective in factor VII-deficient and normal bovine plasma. There were, however, no major differences in the expression of PCA (either cell-associated or shed) between the metastatic and non-metastatic cell types studied. Plasminogen activator (PA) production by these cells has also been measured. The results are discussed in the context of the possible role of fibrin formation and fibrinolysis in the metastatic process.

Adenocarcinoma↗
PubMed2004

How to evaluate phenotype-genotype relationship in rare coagulation haemorrhagic disorders: examples from FVII deficiency.

The study of the molecular pathogenesis of several single-gene disorders, such as coagulation-factor deficiencies, has revealed the variability of phenotypic expression, even of the same mutations in single genes. These studies underline the complexity of research dealing with the definition of the molecular bases of disorders. Sequence variations provide only the starting point to define pathological genotype-phenotype relationships.

Blood Coagulation Disorders↗