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FXI Deficiency (fxi + deficiency)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Screening for factor XI deficiency amongst pregnant women of Ashkenazi Jewish origin

HAEMOPHILIA, Issue 6 2006
R. A. KADIR
Summary., A pilot study was conducted over a 6-month period to evaluate antenatal screening for factor XI (FXI) deficiency amongst Ashkenazi Jewish women booking for their pregnancy in a single obstetric unit. Fifty-four women of Ashkenazi Jewish origin were recruited during their visit for the routine first trimester ultrasound scan. They completed a questionnaire about their personal bleeding symptoms and had blood taken for FXI levels (FXI:C). Seven (13%) women had partial FXI deficiency. Five (9%) were newly diagnosed, and in the remaining two, the diagnosis was known previously. One infant with severe FXI deficiency was identified as a result of maternal testing. This study has shown that FXI deficiency is common amongst women of Ashkenazi Jewish origin and supports its antenatal screening in this population. However, further studies are required to evaluate its cost-effectiveness and the effect on pregnancy outcome. [source]

Successful use of recombinant factor VIIa in a patient with inhibitor secondary to severe factor XI deficiency

HAEMOPHILIA, Issue 2 2002
P. LAWLER
Factor XI (FXI) inhibitors are a rare complication of inherited FXI deficiency. We report the successful use of recombinant factor VIIa (FVIIa) in a patient with a high-responding inhibitor undergoing cataract extraction. At the time of surgery there were limited available data on the optimal management of patients with FXI deficiency. A 62-year-old Ashkenazi Jewish woman had a lifelong history of excessive bleeding secondary to severe FXI deficiency (2 U dL,1), and received FXI concentrate (FXI:C) when she underwent a colposuspension procedure. She was subsequently diagnosed with a FXI inhibitor of 16 Bethesda units (BU) when she developed a poor response to FXI:C at the time of total hip replacement. Two months later she was admitted for cataract extraction. The FXI level was < 1 U dL,1 with an inhibitor titre of 48 BU. She received 90 ,g kg,1 of FVIIa immediately preoperatively followed by continuous infusion at a rate of 20 ,g kg,1 h,1 for 24 h. The cataract extraction was successful and there was no excess bleeding during surgery or in the postoperative period. Mutation analysis of the FXI gene showed that the patient was homozygous for the type II genotype [exon 5, Glu117,Ter]. The reason for the low prevalence of inhibitor formation in patients with FXI deficiency is unclear but may reflect a number of factors including reporting bias, the rarity of absent circulating FXI:C activity, and the infrequent use of FXI replacement therapy. [source]

Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis in mice

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2006
X. WANG
Summary.,Background:,Increased plasma levels of coagulation factor (F) XI are a risk factor for venous thrombosis. Objective:,To further explore the relationship between FXI and venous thrombosis, we evaluated FXI-deficient and wild-type mice in a ferric chloride (FeCl3)-induced vena cava thrombosis model. Methods and Results:,Thrombosis was induced by 3-min topical application of filter papers containing increasing concentrations of FeCl3 and the thrombus was measured at 30 min. In contrast to wild-type mice, FXI-deficient mice failed to form a thrombus with 5% FeCl3, and were partially protected against 7.5% and 10% FeCl3, respectively. The protective effect was substantially stronger than a high dose of heparin (1000 units kg,1, i.v.), clopidogrel (30 mg kg,1, p.o.) or argatroban (30 mg kg,1, i.p.). These antithrombotic agents resulted in off-scale bleeding in a tail bleeding time assay, whereas the bleeding time of FXI-deficient mice was unchanged compared to wild-type mice. In addition to its known effect on the coagulation cascade, enhanced clot lysis was demonstrated in FXI-deficient mouse and human plasma compared to those supplemented with FXIa. Conclusion:,Given the strong antithrombotic efficacy (possibly contributed by strong anticoagulant activity associated with increased fibrinolytic activity) and mild bleeding diathesis associated with FXI deficiency, therapeutic inhibition of FXI may be a reasonable therapeutic strategy to treat or prevent venous thrombosis. [source]

Real-Time quantitative PCR analysis of factor XI mRNA variants in human platelets

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2004
A. Podmore
Summary., Coagulation factor XI (FXI) plays an essential role in blood coagulation. A deficiency of FXI is an unusual hemorrhagic diathesis in that the bleeding tendency can be highly variable, ranging from severe deficiencies with no symptoms to mild and moderate deficiencies requiring multiple blood transfusions for hemorrhages. This variability in bleeding has been attributed to a number of factors including the presence of a novel form of FXI associated with platelets, which ameliorates the bleeding in some cases of FXI deficiency. However, the nature of this platelet FXI molecule is controversial. Hsu et al. (J Biol Chem 1998; 273: 13787,93) suggest that it is a product of normal FXI , but lacking exon V whilst Martincic et al. (Blood 1999; 94: 3397,404) were unable to detect this alternatively spliced variant using RT-PCR. In order to resolve this controversy, we have employed the highly sensitive technique of real-time quantitative RT-PCR using RNA isolated from FXI-deficient patients. Our results indicate that the platelets of both normal and FXI deficient individuals contain FXI mRNA that is identical to the mRNA found in liver. An exon V deleted splice variant was not detected. Thus the FXI message is not alternatively spliced in platelets and therefore would not be able to produce an unusual FXI protein. [source]

A common ancestral mutation (C128X) occurring in 11 non-Jewish families from the UK with factor XI deficiency

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2004
P. H. B. Bolton-Maggs
Summary., Factor XI (FXI) deficiency is a mild bleeding disorder that is particularly common in Ashkenazi Jews, but has been reported in all populations. In Jews, two FXI gene (F11) mutations (a stop codon in exon 5, E117X, type II, and a point mutation in exon 9, F283L, type III) are particularly common, but in other populations a variety of different mutations have been described. In the Basque region of France one mutation, C38R in exon 3, was found in eight of 12 families studied, haplotype analysis suggesting a founder effect. In the course of screening 78 unrelated individuals (including 15 Jewish and 12 Asian) we have found 10 Caucasian non-Jewish patients with the mutation C128X in exon 5. Individuals were investigated because of a personal or family history of bleeding, or finding a prolonged activated partial thromboplastin time. Individuals negative for the type II and type III mutations were screened by a combination of SSCP and heteroduplex analysis. The C128X mutation was found in 10 families (one previously described). Among three individuals with severe FXI deficiency, one was homozygous for the C128X mutation, and two were compound heterozygotes for the C128X and another mutation; other individuals were carriers of the C128X mutation. This is a nonsense mutation producing a truncated protein; individuals have FXI antigen levels concordant with FXI coagulant activity. Haplotype analysis of 11 families, including a further kindred previously reported from the USA, but which originally came from the UK (in which the index patient was homozygous for C128X), suggests a founder effect. [source]

Molecular basis of severe factor XI deficiency in seven families from the west of France.

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2004
Seven novel mutations, including an ancient Q88X mutation
Summary., Inherited factor (F)XI deficiency is a rare disorder in the general population, though it is commonly found in individuals of Ashkenazi Jewish ancestry. In particular, two mutations,a stop mutation (type II) and a missense mutation (type III),which are responsible for FXI deficiency, predominate. The bleeding tendency associated with plasma FXI deficiency in patients is variable, with ,,50% of patients exhibiting excessive post-traumatic or postsurgical bleeding. In this study, we identified the molecular basis of FXI deficiency in 10 patients belonging to six unrelated families of the Nantes area in France and one family of Lebanese origin. As in Ashkenazi Jewish or in French Basque patients, we have identified a new ancient mutation in exon 4 resulting in Q88X, specific to patients from Nantes, that can result in a severely truncated polypeptide. Homozygous Q88X was found in a severely affected patient with an inhibitor to FXI and in three other unrelated families, either as homozygous, heterozygous or compound heterozygous states. Other identified mutations are two nonsense mutations in the FXI gene, in exon 7 and 15, resulting in R210X and C581X, respectively, which were identified in three families. A novel insertion in exon 3 (nucleotide 137 + G), which causes a stop codon, was characterized. Finally, sequence analysis of all 15 exons of the FXI gene revealed three missense mutations resulting in G336R and G350A (exon 10) and T575M (exon 15). Two mutations (T575M and G350A) with discrepant antigen and functional values are particularly interesting because most of the described mutations are associated with the absence of secreted protein. [source]