Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FACTOR IX”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed1982

Factor IX levels during pregnancy in a women with hemophilia B.

The levels of factors VIII, II, and VII rise during pregnancy in normal women. In addition, increases in factor VIII levels have been observed in pregnant carriers of hemophilia A and in women affected with von Willebrand's disease. The influence of pregnancy on factor IX levels is less clear. Consequently, we determined serial factor IX coagulant activities (IX:C) and factor IX antigen levels (IX:Ag) during the pregnancy of an affected carrier of hemophilia B who had baseline values of 13% both IX:C and IX:Ag levels. Neither level rose during pregnancy and the patient was treated with plasmapheresis and plasma infusions during the delivery and the postpartum period. Excessive bleeding did not occur.

Adult↗
PubMed1991

Haemophilia B Leyden arising de novo by point mutation in the putative factor IX promoter region.

Haemophilia B Leyden is characterized by severe factor IX deficiency during childhood with partial resolution at puberty or following the administration of anabolic steroids. The disorder has recently been associated with point mutations in the putative factor IX promoter region, which contains an imperfect direct repeat spanning a possible start site of transcription. We have identified a T to C transition at position +8 in the promoter region of a patient with the haemophilia B Leyden phenotype. A mutation at this site has not been previously reported and occurs within the repeat consensus sequence in the transcribed but untranslated portion of the gene. There is no family history of haemophilia and sequence analysis of his mother and other family members indicates that the mutation has arisen de novo in this patient. This observation provides further support for a causal relationship between point mutations in the presumptive promoter region of the factor IX gene and the Leyden phenotype.

Adult↗
PubMed1985

Characterization of an occult inhibitor to factor IX in a haemophilia B patient.

Six haemophilia B patients were studied while undergoing infusion with factor IX concentrate. All were negative for factor IX antigen (IX:AG) and inhibitor to factor IX coagulant activity (IX:C). One patient showed an atypical response pattern, with prolonged survival of IX:C and IX:Ag. This patient remained under prophylactic treatment and more than 1 year later developed an inhibitor to IX:C of clinical significance. Retrospective study revealed that this patient had significantly higher levels of circulating immune complexes than other haemophilia B patients and in vivo formation of immune complexes containing IX:Ag prior to detection of his inhibitor in conventional clotting assays, suggesting long-term persistence of an occult inhibitor. The inhibitor was shown to be an IgG antibody with both kappa and lambda light chains.

Adult↗
PubMed1999

Factor IX gene analysis in 70 unrelated patients with haemophilia B: description of 13 new mutations.

Seventy unrelated patients suffering from haemophilia B have been screened for determining the molecular defect and for evaluating the spectrum of factor IX mutations in the Rhône Alpes region in France. Most patients were characterized with respect to factor IX antigen and factor IX coagulant activity. We have used denaturing gradient gel electrophoresis to obtain a full scanning of the whole coding, promoter, and exon flanking sequences of the factor IX gene. This technique enabled us to determine the molecular defect in 68 out of 70 families (97%), and the mutation was further identified in the two last patients with a direct sequencing of the gene. A total of 2 complete gene deletions in patients with antifactor IX inhibitor, 6 small insertions/deletions and 62 point mutations were found. Two of these nucleotide substitutions (Arg145His and Ala233Thr) were detected in 21 patients (30%) suggesting the existence of a local founder effect. Thirteen mutations were previously undescribed, including 7 missense mutations. The detection of mutations in patients affected with haemophilia B may shed some light in the structure-function relationship of factor IX molecule within the coagulation system.

Amino Acid Substitution↗
PubMed1977

Spectrophotometric determination of factor Xa generation in factor IX concentrates.

Previous work from this department, concerned with testing the potential thrombogenicity of therapeutic factor IX concentrates, demonstrated that following recalcification of factor IX concentrates thrombin was generated within 3--30 minutes of incubation (Sas el al. 1975). The test developed (known as the TGt 50 test) is a two-stage assay and was thus found to be time consuming, tedious and tended to become inaccurate with long incubation periods and a large number of samples. A semiautomatic version of the test is reported in which the synthetic peptide Bz-ILE-GLU-GLY-ARG-pNA (S-2222) is added to recalcified, diluted factor IX concentrate in the micro-cuvette of a multiple sample recording spectrophotometer. Information can be obtained on (a) the amount of Xa (if any) present prior to recalcification (b) the initial amount of Xa formed and (c) the time taken to activate all factor =X to Xa. Direct graphical interpretation shows a number of qualitative differences between commercial preparations, but by either of the criteria (b) or (c) above, it is possible to place the different products into "activated" and "non activated" groups such that both the Xa generation times and TGt 50 tests identify the same two groups of products. This aggreement also indicates that the TGt 50 test is independent of the intrinsic factor V levels in the various concentrates.

Factor IX↗
PubMedDate not supplied

Expression of active human clotting factor IX from recombinant DNA clones in mammalian cells.

Haemophilia B, or Christmas disease, is an inherited X-chromosome-linked bleeding disorder caused by a defect in clotting factor IX and occurs in about 1 in 30,000 males in the United Kingdom. Injection of factor IX concentrate obtained from blood donors allows most patients to be successfully managed. However, because of impurities in the factor IX concentrate presently in use, this treatment involves some risk of infection by blood-borne viruses such as non-A, non-B hepatitis and the virus causing acquired immune deficiency syndrome (AIDS). Because of the recent concern about the increasing incidence of AIDS amongst haemophiliacs, a factor IX preparation derived from a source other than blood is desirable. Here, we report that after introduction of human factor IX DNA clones into a rat hepatoma cell line using recombinant DNA methods, we were able to isolate small amounts of biologically active human factor IX.

Animals↗
PubMed1984

Spontaneous disappearance of an IgA anti-factor IX inhibitor in a child with Christmas disease.

The few inhibitors to blood coagulation factor IX in patients with Christmas disease (hemophilia B) that have been studied have been shown to belong to the IgG class of immunoglobulins. We report the first case in which a factor IX inhibitor was of the IgA class. Additionally, he appears to be the youngest patient with hemophilia B to have developed an inhibitor. His inhibitor complicated treatment of the patient for several years because of its anamnestic rise following factor IX concentrate administration. It then spontaneously vanished and has not returned in spite of repeated factor IX complex administration.

Antibodies↗
PubMed1987

Expression of human factor IX and its subfragments in Escherichia coli and generation of antibodies to the subfragments.

A cDNA clone encoding the entire human blood clotting factor IX (amino acids -3 to 415 has been placed under control of transcription and translation signals from bacteriophage T7 and expressed in Escherichia coli. The full-length cDNA and 13 different subfragments (which together cover the entire coding sequence of mature factor IX plus amino acids -40 to -19 of the prepro leader sequence) have each been joined to the coding sequence for the major capsid protein of T7 after the 326th codon and expressed as fusion proteins. All of the fusion proteins were insoluble, which facilitated their purification. A goat polyclonal antiserum against human factor IX reacted to different extents with the different fusion proteins, and rabbit polyclonal antibodies raised against the purified fusion proteins recognize the factor IX molecule, as demonstrated by immunoblotting techniques. Antibodies against at least one of the fusion proteins can also inhibit the biological activity of purified factor IX in a one-stage partial thromboplastin time bioassay. We expect these fusion proteins and the antibodies against them to be useful in studying the structure and function of factor IX.

Cloning, Molecular↗
PubMed2000

Application of monoliths for downstream processing of clotting factor IX.

In this paper, the application of monolithic columns for downstream processing of different clotting factor IX concentrates is shown. Determination of basic chromatographic conditions as well as investigations on the regeneration of disk- and tube-shaped monolithic columns using human serum albumin as a model protein, were performed. Separation of factor IX and vitronectin, a possible impurity in commercial factor IX concentrates was accomplished using disk-shaped monolithic columns. These same applications were also carried out with identical results on up-scaled tube-shaped monolithic columns. Since these media allow very fast separations, this method can be successfully applied not only to an in-process control of the purification of factor IX but also to other biopolymers from human plasma. Besides, the same application on the up-scaled tube-shaped monolithic column was successfully carried out.

Biopolymers↗
PubMed1993

Adenovirus mediated expression of therapeutic plasma levels of human factor IX in mice.

Gene therapy strategies designed to combat haemophilia B, caused by defects in clotting factor IX, have so far concentrated on ex vivo approaches. We have now evaluated adenoviral vector-mediated expression of human factor IX in vivo. Injection of the vector Av1H9B, which encodes human factor IX cDNA, into the tail veins of mice resulted in efficient liver transduction and plasma levels of human factor IX that would be therapeutic for haemophilia B patients. However, levels slowly declined to baseline by nine weeks and were not re-established by a second vector injection. These results address both the advantages and obstacles to the use of adenoviral vectors for treatment of haemophilia B.

Adenoviruses, Human↗
PubMedDate not supplied

Changes of coagulation factors IX, VIII, VII, X, and V in nephrotic syndrome.

Plasma procoagulant activities of factors IX, VIII, VII, IX, and V were determined in 21 adult patients with nephrotic syndrome of diverse etiologies. The studies were performed during the initial presentation and prior to institution of any therapy. Procoagulant activities of all these coagulation factors were found to be markedly elevated in a majority of the tested patients. Elevated factor VIII and factor V plasma procoagulant activities demonstrated in this study are in agreement with earlier investigations. None of our patients exhibited acquired factor IX deficiency, a publicized complication of nephrotic syndrome. Instead, the prevalent abnormality was increased plasma factor IX activity in these patients. Our results also suggest that previously reported increased combined factor VII-X activity in nephrotic syndrome is due to elevation of both factor VII and factor X activities.

Adult↗
PubMed1998

High-performance capillary electrophoresis for in-process control in the production of antithrombin III and human clotting factor IX.

Antithrombin III (ATIII) and factor IX (FIX), two proteins from the clotting cascade, were investigated in parallel experiments, using capillary gel electrophoresis and capillary isoelectric focusing. The results from these experiments were compared with the results obtained from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and slab gel isoelectric focusing. In the case of ATIII, capillary gel sieving showed comparable results to SDS-PAGE with the added advantage of the shorter time required for analysis. By optimizing capillary isoelectric focusing (cIEF), a separation of the ATIII isoforms was achieved. In the case of FIX, capillary gel electrophoresis (SDS-CE) of a FIX preparation gave similar results to those obtained by size-exclusion high-performance liquid chromatography and SDS-PAGE, but turned out to be less sensitive in detecting protein impurities at low concentrations. The microheterogeneity of this protein was shown by using cIEF.

Antithrombin III↗
PubMed1994

Factor IX gene haplotypes in Brazilian blacks and characterization of unusual DdeI alleles.

Analysis of factor IX gene polymorphisms is considered the best approach for prenatal diagnosis and carrier detection of haemophilia B when the identification of the gene mutation is not possible. Studies involving factor IX gene polymorphisms in Black populations are scarce and essentially restricted to the North-American Black population whose composition is substantially different from that of the Brazilian and presumably other Black populations of South America. In this paper we report the analysis of eight factor IX gene polymorphisms in Brazilian Blacks: 5' BamHI, DdeI, intron 2 BamHI, XmnI, TaqI, TaqI, MspI, MnlI and HhaI. Characterization of the VNTR-like DdeI polymorphism revealed six different alleles: B, AB, A2B, A2B2, A3B and A5B, the last being described here for the first time. The 5' BamHI, DdeI, MspI and HhaI polymorphisms showed the highest heterozygosities (0.40-0.50) and are in linkage equilibrium with one another. 19 complete haplotypes could be identified in this population. Based on the results we propose a systematic strategy for carrier detection and prenatal diagnosis of haemophilia B in this population. The combined analysis of four polymorphisms (5' BamHI, HhaI, MspI and DdeI) provided an informative genetic marker in 85% of the females. The use of all eight polymorphisms allows information in 95% of females. Additionally, differences in gene frequencies and haplotype distribution suggest dissimilarities in factor IX gene polymorphisms between the Brazilian and the North-American Black populations.

Alleles↗
PubMed1996

A mutation in the propeptide of Factor IX leads to warfarin sensitivity by a novel mechanism.

The propeptide sequences of the vitamin K-dependent clotting factors serve as a recognition site for the enzyme gamma-glutamylcarboxylase, which catalyzes the carboxylation of glutamic acid residues at the NH2 terminus of the mature protein. We describe a mutation in the propeptide of Factor IX that results in warfarin sensitivity because of reduced affinity of the carboxylase for the Factor IX precursor. The proband has a Factor IX activity level of > 100% off warfarin and < 1% on warfarin, at a point where other vitamin K-dependent factors were at 30-40% activity levels. Direct sequence analysis of amplified genomic DNA from all eight exons and exon-intron junctions showed a single guanosine-->adenosine transition at nucleotide 6346 resulting in an alanine to threonine change at residue -10 in the propeptide. To define the mechanism by which the mutation resulted in warfarin sensitivity, we analyzed wild-type and mutant recombinant peptides in an in vitro carboxylation reaction. The peptides that were analyzed included the wild-type sequence, the Ala-10-->Thr sequence, and Ala-10-->Gly, a substitution based on the sequence in bone gamma-carboxyglutamic acid protein. Measurement of C02 incorporation at a range of peptide concentrations yielded a Vmax of 343 cpm/min/reaction for the wild-type peptide, and Vmax values of 638 and 726 for A-10T and A-10G respectively, a difference of only twofold. The Km values, on the other hand, showed a 33-fold difference between wild-type and the variants, with a value of 0.29 microM for wild-type, and 10.9 and 9.50 microM, respectively, for A-10T and A-10G. Similar kinetic experiments showed no substantial differences between wild-type and mutant peptides in kinetic parameters of the carboxylase-peptide complexes for reduced vitamin K. We conclude that the major defect resulting from the Factor IX Ala-l0-->Thr mutation is a reduction in affinity of the carboxylase for the mutant propeptide. These studies delineate a novel mechanism for warfarin sensitivity. In addition, the data may also explain the observation that bone Gla protein is more sensitive to warfarin than the coagulation proteins.

Amino Acid Sequence↗
PubMed1997

Factor IX gene haplotypes in Amerindians.

We have determined the haplotypes of the factor IX gene for 95 Indians from 5 Brazilian Amazon tribes: Wayampí, Wayana-Apalaí, Kayapó, Arára, and Yanomámi. Eight polymorphisms linked to the factor IX gene were investigated: MseI (at 5', nt -698), BamHI (at 5', nt -561), DdeI (intron 1), BamHI (intron 2), XmnI (intron 3), TaqI (intron 4), MspI (intron 4), and HhaI (at 3', approximately 8 kb). The results of the haplotype distribution and the allele frequencies for each of the factor IX gene polymorphisms in Amerindians were similar to the results reported for Asian populations but differed from results for other ethnic groups. Only five haplotypes were identified within the entire Amerindian study population, and the haplotype distribution was significantly different among the five tribes, with one (Arára) to four (Wayampí) haplotypes being found per tribe. These findings indicate a significant heterogeneity among the Indian tribes and contrast with the homogeneous distribution of the beta-globin gene cluster haplotypes but agree with our recent findings on the distribution of alpha-globin gene cluster haplotypes and the allele frequencies for six VNTRs in the same Amerindian tribes. Our data represent the first study of factor IX-associated polymorphisms in Amerindian populations and emphasizes the applicability of these genetic markers for population and human evolution studies.

Brazil↗
PubMed1992

An unusual complication in a gravida with factor IX deficiency: case report with review of the literature.

Factor IX deficiency (hemophilia B, Christmas disease) is an X-linked recessive coagulation disorder. It occurs in one out of every 25,000-30,000 male births and requires even rarer genetic circumstances for phenotypic expression in females. We report the occurrence of a large, late-trimester subchorionic hematoma in a gravida with factor IX deficiency and with laboratory evidence of consumptive coagulopathy during treatment. The patient was managed conservatively and had a successful outcome at term. The only four reported cases of antepartum management of factor IX deficiency in the English literature are reviewed.

Adolescent↗
PubMed1995

Safety of high doses of a monoclonal antibody-purified factor IX concentrate. The Mononine Study Group.

This report summarizes safety and efficacy information among patients treated with high doses (> 75 U/kg) of a monoclonal antibody-purified factor IX concentrate [coagulation factor IX (human) monoclonal antibody purified)] in two clinical trials. One hundred infusions of this factor IX concentrate at doses > 75 U/kg were administered to 35 patients, six of whom had experienced thrombotic complications during previous treatment with prothrombin complex concentrate. Hemostasis in all patients was rated as "excellent," and there were no thrombotic complications.

Adult↗
PubMed1997

Biospecific interactions of vitamin K-dependent factors with phospholipid-like polystyrene derivatives. Part II: factor IX.

We previously demonstrated that phosphorylated polystyrene derivatives exhibit phospholipid-like behaviour and therefore are able to interact with factor II, one of the vitamin K-dependent coagulation factors. Under the same conditions as for factor II, we examined the interactions of factor IX with phosphorylated resins of various compositions in phosphate groups: these studies were carried out with or without albumin precoating of the polymers and either in the presence or absence of calcium ions. Adsorption experiments show that, in the absence of calcium ions, only one class of adsorption sites of factor IX can be evidenced with the interactions taking place through the formation of binary complexes, whereas in the presence of calcium ions, the affinity of factor IX for phosphorylated resins becomes very high and two types of adsorption sites have been evidenced with biospecific ternary complexes being formed. The domains of predominance of these complexes were determined. Moreover, the only functional groups borne by the phosphorylated polystyrene resins involved in factor IX-polymer interactions are phosphodiester groups. Comparison between factor II and factor IX adsorption onto the same polymers leads to the conclusion that the observed differences probably reflect the differences in the Gla domains of the vitamin K-dependent factors. Finally, this study demonstrates that phosphorylated polystyrene derivatives can be used as stationary phases for purification of factor IX by highly specific liquid biochromatography.

Adsorption↗