PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “FACTOR XI”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 55 records · Page 3Linked to original sources
PubMed1984

Acquired factor XI inhibitors in two patients with hereditary factor XI deficiency.

Two patients with hereditary factor XI deficiency developed inhibitors following plasma transfusions. Neither had severe spontaneous bleeding. The patients' plasmas neutralized both factor XI in plasma, purified factor XI, and purified factor XIa. The inhibitor in both patients' plasmas adsorbed to Protein A-Sepharose. The inhibitors eluted from Protein A-Sepharose were partially neutralized by kappa and lambda light chain antisera indicating that they were polyclonal IgG antibodies. Both inhibitors markedly decreased adsorption of factor XI to glass surfaces. The cleavage of factor XI by trypsin was unaffected by the inhibitors. The lack of severe spontaneous bleeding in both of these patients strongly suggests that an alternate coagulation mechanism bypassing factor XI must compensate for this severe defect.

Blood Coagulation Tests↗
PubMed2002

Molecular cloning and biochemical characterization of rabbit factor XI.

Human factor XI, a plasma glycoprotein required for normal haemostasis, is a homodimer (160 kDa) formed by a single interchain disulphide bond linking the Cys-321 of each Apple 4 domain. Bovine, porcine and murine factor XI are also disulphide-linked homodimers. Rabbit factor XI, however, is an 80 kDa polypeptide on non-reducing SDS/PAGE, suggesting that rabbit factor XI exists and functions physiologically either as a monomer, as does prekallikrein, a structural homologue to factor XI, or as a non-covalent homodimer. We have investigated the structure and function of rabbit factor XI to gain insight into the relation between homodimeric structure and factor XI function. Characterization of the cDNA sequence of rabbit factor XI and its amino acid translation revealed that in the rabbit protein a His residue replaces the Cys-321 that forms the interchain disulphide linkage in human factor XI, explaining why rabbit factor XI is a monomer in non-reducing SDS/PAGE. On size-exclusion chromatography, however, purified plasma rabbit factor XI, like the human protein and unlike prekallikrein, eluted as a dimer, demonstrating that rabbit factor XI circulates as a non-covalent dimer. In functional assays rabbit factor XI and human factor XI behaved similarly. Both monomeric and dimeric factor XI were detected in extracts of cells expressing rabbit factor XI. We conclude that the failure of rabbit factor XI to form a covalent homodimer due to the replacement of Cys-321 with His does not impair its functional activity because it exists in plasma as a non-covalent homodimer and homodimerization is an intracellular process.

Amino Acid Sequence↗
PubMed1981

Pseudo-factor-XI deficiency: effect of an inhibitor of factor XI adsorption to surface.

Recently we have described a normal plasma activity that modulates contact activation by inhibiting adsorption of factor XI to activating surfaces. Here we report the first identified case in which a patient has abnormal clotting tests due to an excess of a similar activity. The patient's plasma had a prolonged partial thromboplastin time and low apparent factor XI assay. His plasma prolonged the partial thromboplastin time of normal plasma and partially neutralized normal factor XI activity in vivo and in vitro. Analysis in dilute plasma revealed normal amounts of factor XI activity and antigen. Factor XI adsorption from plasma to activating surfaces was tested by adding a small amount of 125I-labeled purified factor XI to plasma, exposing the mixture to a glass tube or kaolin, and determining the amount of factor XI adsorbed to the surface. Whereas normal plasma and plasmas deficient in factor XII, factor XI, or Fletcher factor yielded about 4% adsorption to glass, factor XI adsorption from patient's plasma was less than 1%, indicating the presence of an adsorption inhibitor. This inhibitor did not affect factor XI activation or the activity of preformed factor XIa. It was not adsorbed by AI(OH)3 and was present in serum and the macroglobulin peak on gel filtration of the plasma through Sephadex G-200. The patient's history does not allow a definitive conclusion as to whether this inhibitor was associated with abnormal bleeding.

Adolescent↗
PubMed1986

Factor XI kinetics after plasma exchange in severe factor XI deficiency.

Plasma exchange in a patient with factor XI deficiency allowed the determination of the factor XI disappearance time. The decay curve showed a biphasic pattern with a t1/2 of h. After a loading dose by means of plasma exchange with fresh frozen plasma (FFP) up to a factor XI level of 65%, administration of 0.5 liter FFP every 12 h was necessary to maintain the factor XI concentration between 40 and 60%. The clearances of factor XI, calculated from the results of plasma exchange and from the maintenance dose, correlated very well and showed that the t1/2 of factor XI did not change after surgery. The patient underwent major surgery uneventfully but ultimately died 3 1/2 weeks after operation from cerebral damage due to cardiac arrest, which occurred on the 2nd postoperative day.

Factor XI↗
PubMed1998

Enhancement of rabbit jugular vein thrombolysis by neutralization of factor XI. In vivo evidence for a role of factor XI as an anti-fibrinolytic factor.

Recent in vitro studies have shown that fibrinolytic activity may be attenuated by a thrombin-activatable fibrinolysis inhibitor (TAFI), which is activated by thrombin, generated via the intrinsic pathway of coagulation in a factor XI-dependent way. Thus factor XI may play a role in the regulation of endogenous fibrinolysis. The aim of this study was to investigate the effect of in vivo inhibition of factor XI and TAFI in an experimental thrombosis model in rabbits. Incorporation of anti-factor XI antibodies in jugular vein thrombi resulted in an almost twofold increase in endogenous thrombolysis compared with a control antibody. A similar effect was observed when the anti-factor XI antibody was administered systemically. Inhibition of TAFI activity also resulted in a twofold increase in clot lysis whereas inhibition of both factor XI and TAFI activity had no additional effect. Thus, we provide the first in vivo evidence for enhanced thrombolysis through inhibition of clotting factor XI, demonstrating a novel role for the intrinsic pathway of coagulation. Furthermore we demonstrate that inhibition of TAFI had a similar effect on thrombolysis. We postulate that inhibition of factor XI activity enhances thrombolysis because of diminished indirect activation of TAFI.

Animals↗
PubMed1992

Expression of human blood coagulation factor XI: characterization of the defect in factor XI type III deficiency.

Human factor XI (FXI) is a blood coagulation factor participating in the early phase of the intrinsic pathway of blood coagulation. It circulates in blood as a glycoprotein composed of two identical chains held together by a single disulfide bond between the fourth apple domains. FXI has been expressed in baby hamster kidney (BHK) cells, where it was synthesized as a single-chain molecule that was converted to the dimer before secretion. The recombinant protein was fully active in a clotting assay, indicating that it interacted readily with other components of the coagulation cascade. A mutant FXI in which Phe283 was converted to Leu (Phe283Leu) was also expressed in BHK cells. This amino acid change occurs in the fourth apple domain of FXI and corresponds to the type III deficiency in Ashkenazi Jews. The mutant protein was secreted at reduced levels (about 8%) compared with normal FXI. This was due to a defect in the dimerization of the molecule rather than a decrease in the transcription of type III messenger RNA. Once secreted, however, the mutant protein consisted of a dimer with full biologic activity. The in vitro expression of FXI indicated that the impaired dimerization and secretion of the Phe283Leu mutant can account for the defect found in patients who are homozygous for the type III FXI deficiency.

Amino Acid Sequence↗
PubMed1977

Factor XI and platelets: Evidence that platelets contain only minimal factor XI activity and antigen.

Factor-XI activity of platelets has been studied in platelet-rich plasmas and isolated platelet suspensions. Fresh platelets in both environments had little or no measurable factor-XI activity. Frozen and thawed platelet-rich normal plasma had markedly elevated apparent factor-XI activity and factor-XI activity as compared to platelet-poor plasma. Frozen and thawed platelet-rich and platelet-poor normal plasmas had equivalent factor-XI antigen. Platelets isolated from normal blood and from factor-XI deficient blood had the same small amounts of apparent factor-XI activity, which increased slightly on freezing and thawing. The data indicates that minimal factor XI is associated with the platelet. The markedly elevated apparent factor-XI activity of frozen and thawed platelet-rich plasma is shown to reflect the interaction of a platelet activator with plasma clotting factors to produce a later activated-clotting-intermediate.

Antigens↗
PubMed2005

Coagulation factor XI: a database of mutations and polymorphisms associated with factor XI deficiency.

Hereditary factor XI deficiency is a rare bleeding disorder that is found worldwide. Rapidly increasing numbers of mutations and polymorphisms in various populations have been reported. However, the number of identified mutations given in recent literature and available databases is named to be not more than 35. We assumed that this is clearly too low and that to date no comprehensive survey of mutations associated with factor XI deficiency is available. To provide a complete database of mutations and polymorphisms associated with factor XI deficiency we collected all available data on hereditary factor XI deficiency from main biological and medical databases [http://ncbi.nlm.nih.gov/pubmed and http://ncbi.nlm.nih.gov/omim (OMIM reference 264900) and the Human Gene Mutation Database for F11 mutations http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/119891.html] as well as from contributions to international congresses. As of 8 June 2004 the number of reported causative mutations is 81, of which 12 have been described in unrelated individuals by more than one study group. For three frequently observed mutations [type II and type III mutations (Gln116Stop and Phe283Leu) and Cys38Arg] common founders have been described. Furthermore, 20 polymorphisms have been described in association with factor XI deficiency, three of which have been reported by two independent study groups. For the majority, allele frequencies have been published for in the Caucasian and/or Black population.

Data Collection↗
PubMed2003

Two factor XI mutations in a Chinese family with factor XI deficiency.

We describe a Chinese family with factor XI deficiency, the first reported to date. The proband had factor XI activity of 1% and was heterozygous for two nonsense mutations, an exon-8 C713-->T mutation resulting in Gln263-->Term, and an exon-10 C979-->A mutation resulting in Tyr351-->Term. Two daughters were heterozygous for the Gln263-->Term mutation and two for the Try351-->Term mutation. All showed a reduction of factor XI activity to about 50%. The Gln263-->Term mutation has been described in two Japanese families, and it remains to be determined whether a common founder exists between the three kindreds. The Try351-->Term mutation is novel.

Asian People↗
PubMed1979

Human platelets and factor XI. Localization in platelet membranes of factor XI-like activity and its functional distinction from plasma factor XI.

Because human platelets participate in the contact phase of intrinsic coagulation and contain a Factor XI-like coagulant activity, the nature of the Factor XI-like activity was examined and compared with purified plasma Factor XI. The platelet factor XI-like activity was sedimented with the particulate fraction of a platelet lysate, was inactivated by heat (t(1/2) 3.5 min, 56 degrees C), was not a nonspecific phospholipid activity, and was destroyed by treatment with Triton X-100. Isolated platelet membranes were four-fold enriched in Factor XI activity and similarly enriched in plasma membrane marker enzymes. The Factor XI-like activity of platelet membranes was detected only when assayed in the presence of kaolin, which suggests that it is present in an unactivated form and can participate in contact activation. Concanavalin A inhibited the Factor XI-like activity of platelet lysates and platelet membranes but not of plasma or purified Factor XI. A platelet membrane-Factor XI complex was isolated after incubation of membranes with purified Factor XI. The Factor XI activity of the platelet membrane-plasma Factor XI complex was inhibited by concanavalin A, whereas unbound plasma Factor XI retained activity. An antibody raised against plasma Factor XI inhibited the in vitro Factor XI activity of plasma and of the platelet membrane-plasma Factor XI complex but had no effect on the endogenous Factor XI-like activity of washed lysed platelets or isolated platelet membranes. Washed platelets and isolated platelet membranes obtained from a Factor XI-deficient donor without a history of excessive bleeding had normal quantities of platelet Factor XI-like activity and normal behavior in the contact phase of coagulation (collagen-induced coagulant activity). These results indicate that platelet membranes contain an endogenous Factor XI-like activity that is functionally distinct from plasma Factor XI.

Antibodies↗
PubMed1988

Transfusion-induced specific anti-factor XI inhibitor in a patient with previously unrecognized factor XI deficiency.

This article reports the rare occurrence and investigation of a specific anti-factor XI inhibitor that arose after fresh-frozen plasma infusion into a patient with previously unrecognized Factor XI deficiency. The IgG fraction of the patient's plasma that contained anti-Factor XI antibody was isolated by chromatography on DEAE-Affigel and concentrated. It was shown to exert inhibitory effect on purified Factor XI and XIa both in the activated and nonactivated partial thromboplastin time assay.

Aged↗
PubMed2001

RETRACTED: Factor XI binding to the platelet glycoprotein Ib-IX-V complex promotes factor XI activation by thrombin.

Factor XI binds to high affinity sites on the surface of stimulated platelets where it is efficiently activated by thrombin. Here, we provide evidence that the factor XI binding site on platelets is in the glycoprotein (GP) Ibalpha subunit of the GP Ib-IX-V complex as follows. 1) Bernard-Soulier platelets, lacking the complex, are deficient in factor XI binding; 2) two GP Ibalpha ligands, SZ-2 (a monoclonal antibody) and bovine von Willebrand factor, inhibit factor XI binding to platelets; 3) by surface plasmon resonance, factor XI bound specifically to glycocalicin (the extracellular domain of GP Ibalpha) in Zn(2+)-dependent fashion (K(d)( app) approximately 52 nm). We then investigated whether glycocalicin could promote factor XI activation by thrombin, another GP Ibalpha ligand. In the presence of high molecular weight kininogen (45 nm), Zn(2+) and Ca(2+) ions, thrombin activated factor XI in the presence of glycocalicin at rates comparable with those seen in the presence of dextran sulfate (1 microg/ml). With higher high molecular weight kininogen concentrations (360 nm), the rate of thrombin-catalyzed factor XI activation in the presence of glycocalicin was comparable with that on activated platelets. Thus, factor XI binds to the GP Ib-IX-V complex, promoting its activation by thrombin.

Animals↗
PubMed1986

Amino acid sequence of human factor XI, a blood coagulation factor with four tandem repeats that are highly homologous with plasma prekallikrein.

A lambda gtll cDNA library prepared from human liver poly(A) RNA has been screened with affinity-purified antibody to human factor XI, a blood coagulation factor composed of two identical polypeptide chains linked by a disulfide bond(s). A cDNA insert coding for factor XI was isolated and shown to contain 2097 nucleotides, including 54 nucleotides coding for a leader peptide of 18 amino acids and 1821 nucleotides coding for 607 amino acids that are present in each of the 2 chains of the mature protein. The cDNA for factor XI also contained a stop codon (TGA), a potential polyadenylation or processing sequence (AACAAA), and a poly(A) tail at the 3' end. Five potential N-glycosylation sites were found in each of the two chains of factor XI. The cleavage site for the activation of factor XI by factor XIIa was identified as an internal peptide bond between Arg-369 and Ile-370 in each polypeptide chain. This was based upon the amino acid sequence predicted by the cDNA and the amino acid sequence previously reported for the amino-terminal portion of the light chain of factor XI. Each heavy chain of factor XIa (369 amino acids) was found to contain 4 tandem repeats of 90 (or 91) amino acids plus a short connecting peptide. Each repeat probably forms a separate domain containing three internal disulfide bonds. The light chains of factor XIa (each 238 amino acids) contain the catalytic portion of the enzyme with sequences that are typical of the trypsin family of serine proteases. The amino acid sequence of factor XI shows 58% identity with human plasma prekallikrein.

Amino Acid Sequence↗
PubMed1980

Surface adsorption of factor XI. Association of adsorption sites with the heavy chain of activated factor XI.

These experiments study surface adsorption of native and activated factor XI using purified radiolabelled human factor XI and trypsin activated factor XI. Both forms of factor XI adsorb not only to glass but also to polypropylene, polyethylene and polystyrene. Albumin (10 mg/ml) markedly reduces adsorption to plastics but not to glass. Sodium dodecyl sulfate prevents adsorption to all surfaces tested. Reduction of 125I-activated factor XI in the presence of sodium dodecyl sulfate yields labelled chains of molecular weight of about 46,000 (heavy chain), 37,000 (light chain) and a further breakdown product of about 26,000. Reduction of activated factor XI in glass or plastic in the absence of sodium dodecyl sulfate yields only light chain and breakdown product in solution; heavy chain is removed by adsorption. Therefore, we conclude that the adsorption site (s) in trypsin activated factor XI and presumably also in native factor XI is (are) located in the heavy chain subunit of the molecule.

Adsorption↗
PubMed1991

A molecular genetic study of factor XI deficiency.

Factor XI deficiency is a rare bleeding diathesis found predominantly in Ashkenazi Jewish kindreds. A recent study of six Jewish patients identified three distinct mutations (Types I, II, and III) in the factor XI gene that were sufficient to fully define the genotypes of the patients. We have investigated 63 patients with factor XI deficiency and find overall allele frequencies of 44% for the type II mutation, 31% for the type III mutation, and 0% for the type I mutation. Therefore, 25% of the mutant factor XI alleles in our sample remain undefined. However, the distribution of mutant alleles is significantly different between Jewish and non-Jewish populations with hitherto undefined mutations accounting for 84% of the disease alleles in non-Jewish patients. Plasma factor XI:C levels were found to differ significantly between different homozygous and compound heterozygous genotypes and the inheritance of the II/III genotype was found to carry an increased risk of the most severe bleeding tendency.

Alleles↗
PubMed1992

Purification of factor XI and some properties of activated factor XI from porcine plasma.

Porcine Factor (F.) XI was purified by following three successive chromatographies. By this procedure, about 5.5 mg of F. XI was obtained from 500 ml of the plasma. The F. XI forms dimer, and is heterogeneous molecule, judging from SDS-polyacrylamide gel electrophoresis. The properties of isolated porcine F. XIa are great similar with those of bovine F. XIa.

Amino Acid Sequence↗
PubMed1994

Coagulation factor XI deficiency in Holstein cattle: expression and distribution of factor XI activity.

Factor XI (F XI) is a plasma protein that participates in the blood coagulation process. A study of the expression of F XI activity in Holstein cattle has confirmed that the inheritance of F XI deficiency is autosomal with severe deficiency in homozygotes (mean F XI level 2%, SD 1%), and partial deficiency in heterozygotes (mean F XI level 38%, SD 10%; normal mean F XI level 94%, SD 21%). In a total of 1469 males evaluated for F XI levels, 47 or 3.1% were identified as heterozygous and only one as homozygous for the disorder. In part because of the lack of a discrete distinction in the expression of F XI between heterozygous and normal animals, not all of the animals tested could be uniquely classified on the basis of the plasma F XI values. A mean F XI value of 53% (SD 7%) was found in a group of animals that were categorized as low normal/high heterozygous. If this group of cattle had been classified on the basis of the criterion used to classify human beings then these animals would have been categorized as heterozygous since the mean F XI value for proven bovine heterozygotes is approximately 20% lower than the values found in the human counterpart. Like the human form of the disease, however, there appears to be a low frequency of hemorrhagic episodes associated with F XI deficiency in cattle.

Animals↗