Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Factor XI Deficiency”

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 55 records · Page 3Linked to original sources
PubMed1999

Factor XI deficiency in women.

Factor XI (FXI) deficiency is an uncommon autosomally transmitted coagulopathy found predominantly in Jewish kindreds. It is associated with variable bleeding tendency that usually manifests after trauma, surgery, or other challenges to hemostasis. Therefore, women with FXI deficiency are at risk of excessive bleeding during their menstrual periods, childbirth, and after surgery. Increased awareness and close collaboration among hematologists, obstetricians, and gynecologists and availability of management guidelines is essential to minimize these risks. This review provides data from current research in FXI deficiency and pregnancy care, menstrual problems, and the role of screening for this disorder in women referred with menorrhagia.

Factor XI Deficiency↗
PubMed1975

Pulmonary embolism with factor XI deficiency.

A patient with factor XI deficiency had pulmonary embolism, although his factor XI assay was less than 1% of normal and his postoperative course was complicated by prolonged bleeding. Programs designed to prevent postoperative venous thrombosis should be carried out in factor XI-deficient patients, since the deficient state offers no protection from a pulmonary embolus. All surgical patients who are to receive low-dose heparin therapy as a part of such a program should be screened by means of preoperative determination of the partial thromboplastin time, to identify previously unsuspected bleeding disorders.

Aged↗
PubMed1993

Postoperative primary adrenal failure from bilateral hemorrhagic adrenal infarction associated with coagulation factor XI deficiency.

A 72-year-old man developed bilateral adrenal hemorrhage causing primary adrenal failure three days after total hip replacement, and was found to have coagulation factor XI deficiency. Factor XI deficiency usually causes mild bleeding which is not predictable on the basis of assayable factor XI levels. There have been no previous reports of bilateral adrenal hemorrhage in factor XI deficiency or other inherited coagulation factor deficiencies. We suggest that the risk of bilateral adrenal hemorrhage should be considered in any preoperative evaluation of patients with factor XI deficiency.

Adrenal Gland Diseases↗
PubMed2004

An Alu-mediated 31.5-kb deletion as the cause of factor XI deficiency in 2 unrelated patients.

Factor XI deficiency (MIM 264900) is an autosomal bleeding disorder of variable severity. Inheritance is not completely recessive as heterozygotes may display a distinct, if mild, bleeding tendency. Recent studies have shown the causative mutations of factor XI deficiency, outside the Ashkenazi Jewish population, to be highly heterogeneous. We studied 39 consecutively referred patients with factor XI deficiency to identify the molecular defect. Conventional mutation screening failed to identify a causative mutation in 4 of the 39 patients. Epstein-Barr virus (EBV)-transformed cells from these 4 patients were converted from a diploid to haploid chromosome complement. Subsequent analysis showed that 2 of the patients had a large deletion, which was masked in the heterozygous state by the presence of a normal allele. We report here the first confirmed whole gene deletion as the causative mutation of factor XI deficiency, the result of unequal homologous recombination between flanking Alu repeat sequences.

Alu Elements↗
PubMed2006

Coagulation factor XI gene analysis in three factor XI deficient Austrian patients.

OBJECTIVES: Hereditary factor XI deficiency is a rare bleeding disorder with worldwide distribution. In Austrian patients only one mutation leading to congenital factor XI deficiency has been reported. In the present study, we identified the molecular basis of factor XI deficiency in three Austrian patients. METHODS: Patients attended hospital for other reasons than bleeding disorders. Routine laboratory tests revealed prolonged APTTs due to decreased factor XI levels. We performed automated fluorescent sequencing of the promotor region, exons 1-15 and the flanking intronic regions of the factor XI gene. The mutations found were confirmed by restriction enzyme analysis or sequencing of the non-coding strand. RESULTS: Fluorescent sequencing revealed two novel mutations, the nonsense mutation Gln116X (443C>T) in exon 5 and a deletion of Ile197 and Asp198 (687_692delTCGACA) in exon 7. Furthermore, we detected a heterozygous A>G exchange at the third nucleotide of IVS6 (IVS 6 +3A>G), which had already been reported in a FXI deficient individual of French Basque origin. CONCLUSION: While the IVS 6 +3A>G decreases the calculated splice consensus score from 0.98 in the wild type to 0.56 in the altered sequence and therefore interferes with the consensus splice sequence, the complete loss of the two amino acids Ile197 and Asp198 is expected to interfere with the steric structure and hence the functions of the third apple domain. The Gln116X leads to a premature termination codon resulting in a lack of the light as well as parts of the heavy chain of the FXI protein, most likely resulting in rapid degradation of the truncated mRNA.

Austria↗
PubMed2006

A novel factor XI gene mutation associated with mild factor XI deficiency in a symptomatic patient.

Congenital factor XI deficiency is a rare condition, in which plasma factor XI levels correlate poorly with the severity of haemorrhage. The condition is typically characterized by post-traumatic bleeding. The factor XI gene is located on chromosome 4 and contains 15 exons. More than 80 mutations have so far been described. We describe a novel mutation in the factor XI gene associated with mild factor XI deficiency. The patient, who is of Irish descent, has a history of post-traumatic bleeding and was found to have a borderline factor XI deficiency. DNA sequence analysis of the factor XI gene revealed a novel T to A mutation at nucleotide 168 resulting in the substitution of the cysteine residue at codon 38 with a stop codon (Cys38STOP). The mutation predicts the premature termination of translation of factor XI mRNA resulting in a truncated, and probably unstable, factor XI protein. The presence of the mutation is consistent with the patient's borderline factor XI deficiency.

Adult↗
PubMed2005

An insertion mutation of the bovine Fii gene is responsible for factor XI deficiency in Japanese black cattle.

Factor XI deficiency in Japanese black cattle is an hereditary mild bleeding disorder with an autosomal recessive mode of inheritance. To characterize the molecular lesion causing factor XI deficiency in cattle, we isolated an entire coding region of the bovine F11 gene, which comprises 15 exons and 14 introns, and determined its nucleotide sequences. Comparison of the nucleotide sequences of the F11 gene between affected and unaffected animals revealed an insertion of 15 nucleotides in exon 9 of the affected animals. The insertion results in a substitution of one amino acid with six amino acids in a highly conserved amino acid sequence in the fourth apple domain of factor XI protein. Genotyping of the F11 gene in 109 Japanese black cattle revealed that the insertion clearly corresponded to the factor XI activities of the animals. We therefore concluded that the insertion of 15 nucleotides in the F11 gene is the causative mutation for factor XI deficiency in Japanese black cattle. Genotyping of the F11gene by detecting the insertion will be an effective DNA-based diagnostic system to prevent incidence of the disease.

Amino Acid Sequence↗
PubMed1991

Factor XI deficiency acquired by liver transplantation.

Factor XI deficiency (the Rosenthal syndrome), an autosomal recessive genetic defect, was transmitted to a patient after orthotopic liver transplantation. The deficiency was manifested by an isolated prolonged activated partial thromboplastin time (aPTT) after surgery. Hematologic evaluation using specific factor analysis revealed an absolute deficiency of factor XI. Stored serum obtained from the organ recipient before transplantation showed normal factor XI levels. When the liver donor's family was questioned, it was discovered that he was of Ashkenazi Jewish descent and that he had a history of bleeding after dental procedures. Before his death from intracerebral bleeding, he was documented to have an isolated prolonged aPTT value. This case shows that potentially morbid genetic defects can be transmitted by organ transplantation. It also provides evidence confirming that the liver is the only site of factor XI production.

Factor XI Deficiency↗
PubMed1982

Acquired antibody to factor XI in a patient with congenital factor XI deficiency.

The results of studies in a patient with congenital deficiency of Factor XI who developed an inhibitor are presented. The patient presented with a severe, apparently spontaneous bleed into the thigh, which progressed despite infusion of fresh frozen plasma, but which responded promptly to activated prothrombin complex. During therapy with plasma his clotting time and Factor XI level were unresponsive and a Factor XI inhibitor titer of 6,000 U/ml was attained. The inhibitor was isolated and found to be polyclonal immunoglobulin G (IgG), predominantly of subclass 4. The specificity of the antibodies for Factor XI was shown by the ability of isolated inhibitor bound to polyacrylamide beads to remove Factor XI selectively from normal plasma. The binding of (125)I-labeled factor XI to the inhibitor was studied and an affinity constant of 1.65 x 10(10) liter/mol was found. Complexing of the antibodies with Factor XI was shown to block multiple activities of the clotting factor. Factor XI complexed with antibody did not bind to high molecular weight kininogen or undergo activation and cleavage by two-chain Factor XII. The complex of activated Factor XI with inhibitor prevented the cleavage and activation of Factor IX. Hence the inhibitor appears to act by binding to multiple sites on the Factor XI molecule and preventing its interaction with other molecules. Clinically these interactions of the inhibitor with Factor XI result in a state of severe Factor XI deficiency. The clinical circumstances of the case, with severe hemorrhage refractory to plasma infusion but readily responsive to an alternate clot-promoting agent, suggest that a defect of intrinsic system activation was critical, supporting the inference that Factor XI does participate in normal hemostasis. The clinical course of this patient, who has only had two documented hemorrhages in the presence of the inhibitor, is not as severe as that of patients with severe Factor VIII or IX deficiency. This suggests that physiologic activation of Factors XI and IX does not occur exclusively in series because deficiency of factors XII, XI, VIII, and IX should then have similar hemostatic consequences. We propose that independent mechanisms for bypass of Factors XII and XI are important in physiologic activation of coagulation.

Animals↗
PubMed2004

Dominant factor XI deficiency caused by mutations in the factor XI catalytic domain.

The bleeding diathesis associated with hereditary factor XI (fXI) deficiency is prevalent in Ashkenazi Jews, in whom the disorder appears to be an autosomal recessive condition. The homodimeric structure of fXI implies that the product of a single mutant allele could confer disease in a dominant manner through formation of heterodimers with wild-type polypeptide. We studied 2 unrelated patients with fXI levels less than 20% of normal and family histories indicating dominant disease transmission. Both are heterozygous for single amino acid substitutions in the fXI catalytic domain (Gly400Val and Trp569Ser). Neither mutant is secreted by transfected fibroblasts. In cotransfection experiments with a wild-type fXI construct, constructs with mutations common in Ashkenazi Jews (Glu117Stop and Phe283Leu) and a variant with a severe defect in dimer formation (fXI-Gly350Glu) have little effect on wild-type fXI secretion. In contrast, cotransfection with fXI-Gly400Val or fXI-Trp569Ser reduces wild-type secretion about 50%, consistent with a dominant negative effect. Immunoprecipitation of cell lysates confirmed that fXI-Gly400Val forms intracellular dimers. The data support a model in which nonsecretable mutant fXI polypeptides trap wild-type polypeptides within cells through heterodimer formation, resulting in lower plasma fXI levels than in heterozygotes for mutations that cause autosomal recessive fXI deficiency.

Adult↗
PubMed1996

[Factor XI deficiency: do patients with hemorrhagic diathesis also have hemostasis defects?].

It is well known that the extent of bleeding in patients with a deficiency of factor XI does not parallel the residual factor activity. Therefore, additional hemostatic aspects must be taken into consideration. 27 patients of 18 different families--6 with severe (FXI < 0.01 to 0.09 U/ml) and 21 with moderate (FXI 0.20 to 0.252 U/ml) factor XI deficiency--were reinvestigated regarding hemostasis including bleeding time and platelet function. 16 had an enhanced bleeding tendency, while the others--including 3 with severe FXI deficiency of < 0.01 U/ml--never suffered from bleeding complications despite delicate surgery in some. All 16 of the symptomatic patients had, besides the reduction of factor XI activity to various extents, an additional hemostatic defect: 3 had a moderate alpha/delta storage pool detect of the platelets, 11 a platelet anomaly mainly characterized by reduced ADP aggregation and 2 an isolated prolonged bleeding time of unknown cause. Synthesis of platelet thromboxane was unimpaired in all patients as tested by formation of malondialdehyde after stimulation with N-ethyl maleimide. Hence, in patients with a known factor XI deficiency diagnostic and prophylactic measures before surgery should concentrate on such additional findings. Preoperative administration of desmopressin, and not replacement of factor XI, will be the treatment of choice in these cases.

Adult↗
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↗
PubMed2003

[Identification of two novel factor XI non-sense mutation Trp228stop and Trp383stop in a Chinese pedigree of congenital factor XI deficiency].

OBJECTIVE: To identify the factor XI gene mutation in a Chinese pedigree of congenital factor XI deficiency. METHODS: The peripheral blood samples were collected from the proband and her family members and the plasma FXI:C and FXI:Ag were assayed. All the exons and their adjacent intron sequences of factor XI were amplified with PCR and sequenced thereafter. RESULTS: Two novel nonsense mutations TGG-->TGA (Trp228stop) and TGG-->TAG (Trp383stop) were identified in the family. CONCLUSION: The compound heterozygous Trp228stop and Trp383stop may attribute to the pathogenesis of the congenital factor deficiency.

Adult↗
PubMedDate not supplied

Factor XI deficiency: literature review and case presentation.

Factor XI deficiency is a rare hereditary bleeding disorder affecting the intrinsic pathway. Understanding the pathophysiology and clinical significance of this disease entity can help avoid potentially hazardous sequelae. This case presentation discusses laboratory criteria and serum assaying techniques utilized to appropriately manage preoperative or post-traumatic patients suffering from factor XI deficiency.

Aged↗
PubMed1992

Dental surgery in patients with severe factor XI deficiency without plasma replacement.

Bleeding following dental extraction is frequently the first manifestation of severe factor XI deficiency. Safe oral surgery has previously been performed in such patients by using plasma replacement therapy with or without concomitant administration of antifibrinolytic agents. The aim of this study was to determine whether such patients can undergo safe dental extractions using only an antifibrinolytic agent. The study group consisted of 19 patients with severe factor XI deficiency (factor XI:C level less than 14 U/dl) who had previously bled following dental extractions (14 patients) or other trauma (five patients). Tranexamic acid, 1 g q.i.d., was given from 12 h before surgery, until 7 days afterwards. No excessive bleeding was observed following dental extractions. One patient had slight oozing after 3 days which ceased spontaneously. Thus, plasma replacement no longer appears necessary for patients with severe factor XI deficiency requiring dental extractions.

Adult↗
PubMed1978

Factor XI deficiency: detection and management during urological surgery.

Hereditary factor XI deficiency may remain undiagnosed until severe bleeding is observed after an operation or trauma. Two such cases were encountered and, therefore, a regular screening test for coagulation disorders among urological patients was initiated. During 2 years (1975 and 1976) 10 additional cases of factor XI deficiency were detected: 5 severe and 5 partial. All patients were Ashkenazic Jews of Eastern European origin. The 5 patients with severe factor XI deficiency underwent an operation without any complications. They were transfused with 5 to 20 ml./kg./day of fresh frozen plasma from the day before the operation until 10 to 14 days postoperatively. Of the 5 patients with partial XI deficiency 4 underwent an operation. In 1 of 3 patients who did not receive transfusions postoperative bleeding was observed. A minimal level of 0.3 U./ml. (30 per cent) factor XI was found necessary to ensure good hemostasis during and after an operation. In view of a recent finding of relatively high gene frequency of factor XI deficiency in Ashkenazic Jews it seems warranted to do a partial thromboplastin time in such patients who need an operation.

Adult↗
PubMed2005

Co-existence of Bernard Soulier syndrome and factor XI deficiency in a family: a unified pathology?

Bernard Soulier syndrome (BSS) is an autosomal recessive disorder of platelet function. Factor XI deficiency leads to a variable bleeding tendency and the defect is also inherited in an autosomal recessive manner. In this paper we describe a case of BSS with severe deficiency of factor XI. The patient had both BSS and factor XI deficiency. The sister and both the parents were heterozygous for BSS and had factor XI deficiency. The brother is normal for both BSS and factor XI levels. Apart from the patient, no other family members had any history of bleeding in spite of having a deficiency of factor XI, which suggests that low level of factor XI in this family was not responsible for bleeding. Curiously, although the index patient inherited both Bernard Soulier syndrome and factor XI deficiency (FXI: C = 1.3%), he had mild bleeding symptoms restricted only to ecchymoses and petechiae. Detailed review of the pedigree showed that all the members who inherited the BSS phenotype, also inherited abnormal factor XI gene. Karyotype of the affected members of the family using standard Giemsa banding technique showed a normal picture. Considering the fact that the genes causing both BSS and factor XI are both on widely different chromosomes, their coinheritance in four members of the family without any unusual translocation suggest a unified pathology probably on the basis of a common transcription factor defect or a common post translational processing defect. This is the first case of coinheritance of BSS and factor XI deficiency reported in the English literature.

Bernard-Soulier Syndrome↗
PubMed1990

The effect of combined factor XI deficiency with von Willebrand factor abnormalities on haemorrhagic diathesis.

To account for the lack of correlation between the level of factor XI (FXI) in deficient patients and haemorrhagic manifestations, we correlated the prevalence of combined FXI and von Willebrand's factor (vWF) deficiency in 212 FXI-deficient patients. Fifty-four patients had a combined FXI and vWF deficiency: 16 patients had severe and 38 patients had mild FXI deficiency. In a group of 28 patients with comparably mild FXI deficiency, 14 bleeders had significantly lower mean vWF, Ag, ristocetin cofactor and ristocetin induced platelet aggregation than 14 non-bleeders selected on the basis of comparable FXI levels. These findings suggest that the combination of FXI and vWF deficiency is common and may affect the bleeding tendency in mild FXI deficiency.

Adolescent↗