Original Article
Factor XI Deficiency in Ashkenazi Jews in Israel
N Engl J Med 1991; 325:153-158July 18, 1991
- Abstract
- Abstract
Background and Methods.
Severe factor XI deficiency, which is relatively common among Ashkenazi Jews, is associated with injury-related bleeding of considerable severity. Three point mutations — a splice-junction abnormality (Type I), Glu117→Stop (Type II), and Phe283→Leu (Type III) — have been described in six patients with factor XI deficiency. Clinical correlations with these mutations have not been carried out. We determined the relative frequency of the mutations and their association with plasma levels of factor XI clotting activity and bleeding, analyzing the mutations with the polymerase chain reaction and restriction-enzyme digestion.
Results.
The Type II and Type III mutations had similar frequencies among 43 Ashkenazi Jewish probands with severe factor XI deficiency; these two mutations accounted for 49 percent and 47 percent, respectively, of a total of 86 analyzed alleles. Among 40 of the probands and 12 of their relatives with severe factor XI deficiency, patients homozygous for Type III mutation had a significantly higher level of factor XI clotting activity (mean [±SD] percentage of normal values, 9.7±3.8 percent; n = 13) than those homozygous for Type II mutation (1.2±0.5 percent, n = 16) or compound heterozygotes with Type II/III mutation (3.3±1.6 percent, n = 23), as well as significantly fewer episodes of injury-related bleeding. Each of these three groups had a similarly increased proportion of episodes of bleeding complications after surgery at sites with enhanced local fibrinolysis, such as the urinary tract, or during tooth extraction.
Conclusions.
Type II and Type III mutations are the predominant causes of factor XI deficiency among Ashkenazi Jews. Genotypic analysis, assay for factor XI, and consideration of the type and location of surgery can be helpful in planning operations in patients with this disorder. (N Engl J Med 1991; 325:153–8.)
Media in This Article
Figure 1
Pedigrees of Four Ashkenazi Jewish Families, Showing the Variety of Genotypes Associated with Factor XI Deficiency.Figure 2
Pedigree and Electrophoretic—Immunoblot Analysis of an Iraqi Jewish Family with Factor XI Deficiency.Article Activity
- Article
FACTOR XI (plasma thromboplastin antecedent, or PTA) is a plasma glycoprotein (molecular weight, 140,000) that participates in the early phase of the intrinsic pathway of the blood-coagulation cascade. It circulates in plasma in a precursor form and is converted to an active serine protease by minor proteolysis. The gene coding for the protein has been characterized and shown to be 23 kilobases long and composed of 15 exons and 14 introns.1 It is located on the distal end of the long arm of chromosome 4 (4q35).2 A deficiency of factor XI is an unusual coagulopathy in that it has extreme variability in its bleeding manifestations, ranging from a complete absence of symptoms to injury-related bleeding that requires multiple transfusions.3 , 4 Unlike the hemophilias, factor XI deficiency is rarely manifested as spontaneous bleeding; the associated bleeding usually occurs after trauma, surgery, or other challenges to hemostasis. The bleeding tendency may also vary in the same patient if such challenges are repeated.5
Factor XI deficiency is inherited as an autosomal recessive trait that is characterized by a very low level (0 to 10 percent) of circulating factor XI antigen in homozygotes, in whom both alleles carry mutations that render the patients incapable of expressing normal levels of factor XI. Thus far, the majority of these patients have been found to have a parallel reduction in factor XI activity and the level of circulating factor XI antigen, signifying a deficiency in the plasma concentration of the protein (reduced cross-reacting material).6 , 7 To date, only three cases of disease have been reported in which the factor is present but functionally defective.7 , 8 The nature of the underlying genetic lesions in all these patients is unknown.
A striking aspect of factor XI deficiency is that it occurs predominantly in Jewish persons of Ashkenazi descent. In a previous study, the frequency of homozygotes in Israel was shown to be about 1 in 190, making the disorder one of the most prevalent genetic defects in this population.4 Factor XI deficiency has also been reported in non-Jewish patients, including patients of Japanese, Korean, Chinese, German, Italian, African American, English, Indian, and Arab ancestry.6 , 7 However, these patients are extremely rare — about 1 per million population.9
In a recent study, three independent point mutations in the factor XI gene were identified that accounted for the deficiency of the protein in six Ashkenazi Jews.10 These mutations were designated Types I, II, and III. The Type I mutation, which was least prevalent, occurred at an intron—exon boundary and apparently disrupted normal messenger RNA splicing. The Type II mutation was a nonsense mutation that converted Glu117 (GAA) to a stop codon (TAA) and resulted in premature termination of translation. The Type III mutation was a missense mutation and resulted in the substitution of Leu (TCT) for Phe283 (TCC) in the protein. Rapid assays for each of the three types of mutations have been developed. These assays use the polymerase chain reaction to amplify regions of the factor XI gene encompassing the three mutation sites. Since restriction sites are either abolished or created by each of these mutations, their presence or absence is readily determined by restriction-endonuclease digestion and subsequent gel electrophoresis. In the present investigation, we studied patients with severe factor XI deficiency who were members of 52 unrelated families residing in Israel, analyzing their genotypes, levels of circulating factor XI, and bleeding histories.
Methods
Clinical Evaluation, Coagulation Tests, and Statistical Analysis
We studied 49 unrelated Ashkenazi probands with factor XI deficiency (43 homozygotes and 6 heterozygotes) who were living in Israel and 53 of their relatives with factor XI deficiency, including 12 homozygotes and 41 heterozygotes. Patients were considered to be homozygous if their factor XI clotting activity (factor XI:C) ranged from 1 to 14 percent, and to be heterozygous if their factor XI:C levels ranged from 28 to 60 percent. Three other homozygous probands with factor XI deficiency, two Iraqi Jews and one Arab, were also studied.
A detailed history of spontaneous bleeding and injury-related episodes of bleeding was obtained from 40 of the 43 Ashkenazi probands and from 12 of their affected relatives. Blood samples for genotypic analysis (see below) and for factor XI:C assay were taken from all probands and relatives with factor XI deficiency as well as from 58 healthy Ashkenazi Jewish controls.
The factor XI:C level and the activated partial-thromboplastin time (APTT) were determined as described by Rapaport et al.3 In these tests, pooled plasma samples from 49 healthy subjects (hospital personnel) of different ethnic origins, including some Ashkenazi Jews, served as controls.
The association between the proband's genotype and the number of spontaneous or injury-related bleeding events was analyzed with Fisher's exact probability test.11 Only injury-related bleeding events not treated by replacement therapy (i.e., events occurring before the diagnosis was established) were included in the analysis. Fisher's exact test was also used to compare groups for factor XI:C levels to adjust for the inequality of variances. Student's t-test was used to compare APTT values. Results are presented as means ±SD.
DNA Preparation and Polymerase Chain Reaction—Restriction-Enzyme Assay
Total genomic DNA from each subject was isolated from 1 ml of whole blood according to the method of Bell et al.12 Analysis for the three types of point mutations by means of the polymerase chain reaction and restriction-enzyme digestion was performed as described previously.10 The polymerase chain reaction was performed with 0.5 μg of genomic DNA in the presence of 100 pmol of each of two specific oligonucleotide primers13 and 0.5 unit of Taq polymerase (Perkin–Elmer–Cetus). Amplification was carried out for 35 cycles in a thermal cycler (Perkin–Elmer–Cetus) under the following conditions: one minute at 94°C for denaturation, two minutes at 60°C for annealing of DNA with primers, and three minutes at 72°C for primer extension. The amplified DNA products were then digested with specific restriction enzymes whose substrate-specific sequences were altered by the mutations: MaeIII for Type I mutation, BsmI for Type II mutation, and Sau3AI or MboI for Type III mutation.10 The digested products were analyzed on an agarose gel containing 2 percent NuSieve agarose and 1 percent SeaKem agarose (FMC BioProducts) in the presence of ethidium bromide.
Factor XI Purification and Western Blotting
Factor XI was partially purified from the plasma of a healthy donor and from the plasma of a patient homozygous for Type III mutation, according to the method of Bouma and Griffin.14 Seven milliliters of plasma was first dialyzed at room temperature against 40 mM TRIS—hydrochloride buffer (pH 8.3) containing 10 mM succinate and then chromatographed on a DEAE-Sepharose CL-6B column. The pass-through fraction, which contains factor XI, was collected and dialyzed against 20 mM TRIS—hydrochloride buffer (pH 7.2) containing 0.2 M sodium chloride and chromatographed on a heparin—agarose column. Factor XI was eluted with high-ionic-strength buffer (20 mM TRIS—hydrochloride buffer, pH 7.2, containing 0.6 M sodium chloride). The partially purified factor XI preparation was concentrated and desalted in a Micro-ProDicon apparatus (Bio-Molecular Dynamics).
Partially purified factor XI was analyzed by slab sodium dodecyl sulfate–polyacrylamide-gel electrophoresis performed according to the method of Laemmli.15 The proteins were transferred onto a nitrocellulose membrane as described by Towbin et al.16 Human factor XI was detected with a solid enzyme-linked immunosorbent assay using rabbit antihuman factor XI (0.5 fig per milliliter), biotinylated goat—antirabbit IgG (Bethesda Research Laboratories), and streptavidin—alkaline phosphatase conjugate for band visualization.
Results
Relative Frequency of Genotypes among Patients with Factor XI Deficiency
Genotypic analyses were carried out for 46 unrelated probands from Israel with severe factor XI deficiency. Forty-three of these patients were of Ashkenazi Jewish descent, one was an Arab, and two were of Iraqi Jewish descent. Of the 86 defective genes among the Ashkenazi Jewish patients, 42 genes contained Type II mutations, 40 contained Type III mutations, 1 had an Osaka-I mutation (see below), and 3 had unidentified mutations. No Type I mutations were observed. The frequency of Type II and Type III defective alleles was 49 percent and 47 percent, respectively. The proportion of Type II/II homozygotes to Type II/III compound heterozygotes and to Type III/III homozygotes was 10:20:10. Three Ashkenazi Jewish patients were compound heterozygotes, each of whom carried one unidentified defective gene. In two of these three patients the second allele carried the Type II mutation, and in the third patient the second allele contained a nonsense mutation identical to that found in a Japanese patient (Osaka-I) (unpublished data). Of the 58 Ashkenazi Jewish healthy controls, 2 were identified as heterozygous for Type II mutation. The variety of mutant genotypes associated with factor XI deficiency is shown in the pedigrees of four Ashkenazi Jewish families (Fig. 1Figure 1
Pedigrees of Four Ashkenazi Jewish Families, Showing the Variety of Genotypes Associated with Factor XI Deficiency.).The two Iraqi Jewish probands and the Arab proband with severe factor XI deficiency were homozygous for Type II mutation. A genotypic analysis of the immediate relatives of one Iraqi Jewish proband is shown in Figure 2Figure 2
Pedigree and Electrophoretic—Immunoblot Analysis of an Iraqi Jewish Family with Factor XI Deficiency.. In this family, both the proband and a sibling were homozygous for Type II mutation, whereas the parents were heterozygous for Type II mutation and another sibling was normal.Genotype and Factor XI Clotting Activity
Factor XI:C levels were compared according to genotypes comprising Type II mutations, Type III mutations, or both, in 99 subjects from 46 unrelated families. The results (Table 1Table 1
Factor XI:C Levels and APTT in Ashkenazi Jews with Factor XI Deficiency and Controls, According to Genotype.*) showed that Type III/III homozygotes had a significantly higher mean factor XI:C level (expressed as a percentage of normal values) than did Type II/II homozygotes (9.7 percent vs. 1.2 percent). Type II/III compound heterozygotes had an intermediate value for factor XI:C (3.3 percent), which differed significantly from both the value for Type II/II homozygotes and that for Type III/III homozygotes. These data are consistent with the concept that the Type II mutation, which causes premature chain termination, produces little if any circulating factor XI:C. In contrast, each allele for the Type III mutation, which results in an amino acid substitution, produces a factor XI activity level of approximately 5 percent. The mean activity level of 10 percent observed in Type III/III homozygotes was therefore attributed to the presence of two copies of the Type III allele, each contributing about 5 percent of the factor XI circulating in blood. Heterozygotes for Type III mutation (III/—) also had a significantly higher mean factor XI:C level than did Type II/—heterozygotes (Table 1).The significant differences in factor XI:C levels among the groups with genotypes II/II, II/III, and III/III were also demonstrable in the APTT values. The group with genotype III/III had the lowest mean value, whereas the group with genotype II/III had intermediate values. Heterozygotes for Type II mutation (II/—) and Type III mutation (III/—) had similar mean APTT values (Table 1).
Genotype and Bleeding Manifestations
Spontaneous bleeding manifestations (epistaxis, ecchymoses, menorrhagia, hematuria, and gastrointestinal bleeding) were reported infrequently by the 52 patients with severe factor XI deficiency. The mean number of episodes of spontaneous bleeding in the 16 patients with genotype II/II was 0.63±0.96, the number in the 23 with genotype II/III was 0.57±0.66, and the number in the 13 with genotype III/III was 1.0±1.1. The differences between these groups were not significant.
In contrast, the mean number of injury-related bleeding events after tooth extraction, surgery, and childbirth (without replacement therapy) was significantly lower in the patients with genotype III/III (1.0±1.1) than in those with genotype II/II (1.6±2.4, P<0.05) and those with genotype II/III (1.4±1.5, P<0.05). Furthermore, none of the 13 patients with genotype III/III had three or more injury-related bleeding events, whereas 4 of the 16 patients with genotype II/II and 6 of 23 with genotype II/III did have three or more such events.
Injury-related bleeding was also analyzed in patients with genotype II/II, II/III, or III/III who had undergone surgical procedures (performed without plasma replacement) that were complicated by excessive bleeding (Table 2Table 2
Proportions of Surgical Procedures Complicated by Bleeding in Patients with Severe Factor XI Deficiency.). Surgical procedures that involved tissue with an enhanced local fibrinolytic activity (the urinary tract, nose, and tonsils) were frequently accompanied by excessive bleeding in all patients irrespective of their genotype. The proportion of patients with bleeding complications after such surgical procedures (12 of 16 patients) was significantly higher than the proportion with such complications after other operations, such as appendectomy, cholecystectomy, hysterectomy, or orthopedic surgery (8 of 38 patients, P<0.001). Interestingly, among the patients who had these other types of operations, bleeding complications occurred in 4 of 8 patients with genotype II/II, but in only 3 of 20 patients with genotype II/III and 1 of 10 with genotype III/III.Tooth extractions, which involve another tissue high in profibrinolytic components, were also frequently accompanied by excessive bleeding in all patients irrespective of their genotype (Table 2). In contrast, only 1 of 22 patients (an infant with genotype II/III) had excessive bleeding after circumcision. These data suggest that both the genotype and the specific tissue traumatized by surgery affect the incidence of bleeding in patients with severe factor XI deficiency.
Presence of Factor XI in Plasma of Type III Homozygotes
A previous study found good correlation between the levels of factor XI:C and factor XI antigen in 63 Ashkenazi Jews homozygous for factor XI deficiency according to phenotypic analysis.6 In the present study, the genotypes of 10 of these patients were analyzed and their factor XI:C levels were compared with their previously determined factor XI antigen levels. The mean factor XI antigen level was less than 1 percent in patients with genotype II/II (n = 3), 3.0±1.0 percent in those with genotype II/III (n = 3), and 10.0±2.2 percent in those with genotype III/III (n = 4). These antigen levels were reduced in direct proportion to the decrease in levels of clotting activity, which were as follows: less than 1 percent in patients with genotype II/II, 2.7±1.2 percent in those with genotype II/III, and 12.3±2.4 percent in those with genotype III/III. To characterize further the factor XI of a Type III/III homozygote, the protein was partially purified and analyzed by Western blot experiments, together with normal factor XI purified from plasma of a healthy subject (Fig. 2). Factor XI from the patient with genotype III/III comigrated with normal factor XI in reduced (lanes 3 and 4) and unreduced (lanes 1 and 2) sodium dodecyl sulfate–polyacrylamide gels, showing that its molecular weight and ability to dimerize were apparently identical to those of normal factor XI. These data suggest that the plasma from patients with genotype III/III contained functional factor XI with a specific activity that was apparently the same as that of normal factor XI, but was present in reduced amounts.
Identifying Heterozygous Carriers
Great variation in the factor XI clotting activity was observed among both the Ashkenazi Jewish controls (45 to 205 percent) and the heterozygous carriers of factor XI deficiency (Type II, 28 to 126 percent; Type III, 29 to 108 percent). Consequently, there was a significant overlap between the values of the controls and those of the carriers. Thus, in many cases, measurements of clotting activity in possible carriers may not conclusively differentiate a normal subject from a carrier. The polymerase chain reaction combined with restriction-enzyme analysis, as employed in this study, definitively identified heterozygous carriers.
Discussion
The data presented in this study indicate that nearly all Ashkenazi Jewish patients with severe factor XI deficiency carry Type II or Type III mutations (or both). The relative frequencies of these mutations in the general Ashkenazi Jewish population seem to be equal, in view of our finding that the number of compound heterozygotes (Type II/III) was twice as high as either Type II/II or Type III/III homozygotes. Interestingly, two unrelated probands of Iraqi Jewish origin were homozygous for the Type II mutation. Both probands had nonconsanguineous parents. This finding suggests that factor XI deficiency among Jews that is caused by the Type II mutation is not confined to the Ashkenazi community. The Iraqi Jewish community, of which approximately 270,000 members reside in Israel, represents a segment of the original gene pool of the Jewish people who stayed in the Middle East in relative isolation for 2500 years.17 If more cases of only the Type II mutation are found in this population, such a finding might indicate that this mutation among Ashkenazi and Iraqi Jews is due to a common founder effect. The high frequency of factor XI deficiency among Ashkenazi Jews may be attributed to extreme genetic drifts caused by drastic changes in population size, migration, and founder effects that accounted for the development of whole communities from relatively few individuals. The relative isolation of the Ashkenazi population from other groups within host countries because of religious and cultural differences presumably has prevented the spread of this mutant gene into the general population. The fact that the abnormality has remained in this population suggests that the factor XI gene may be linked or closely associated with some very favorable trait (or traits) carried from generation to generation. Present evidence shows that the Type III mutation is found exclusively among Ashkenazi Jews and suggests that this mutation might have occurred at a later time, presumably after the divergence of the Jewish population into Ashkenazi, Sephardic, and Asian Jewish communities. The reasons for the high frequency of the Type III mutation are probably the same as for the frequency of the Type II mutation.
Levels of factor XI antigen and factor XI:C were previously shown to be equally reduced in 78 patients with severe factor XI deficiency.6 In the present study, the biochemical properties of factor XI purified from the plasma of a Type III/III homozygote appeared to be normal (Fig. 2). These data suggest that the conversion of Phe283 to Leu in persons with the Type III mutation affects some other events in the biosynthesis or secretion of factor XI from the liver. Alternatively, the Type III-mutant factor XI is predisposed to rapid decay. Factor XI, as well as plasma prekallikrein, is present in the circulation as a complex with high-molecular-weight kininogen (HK).18 , 19 The first tandem repeat, or "apple domain," is the site for the binding of factor XI to HK,20 whereas the carboxylterminal portion of the heavy chain of prekallikrein contains the binding site of prekallikrein to HK.21 Since the Type III mutation of factor XI consists of an amino acid substitution in the fourth apple domain, it is unlikely that the mutation could result in diminished binding of the protein to HK or, consequently, in an accelerated removal of factor XI from the circulation. Expression experiments using a complementary DNA that contains the Type III mutation should be conducted to examine the effect of this amino acid substitution on intracellular transport, secretion, turnover in plasma, and interaction with HK.
Previous studies have shown that some patients with severe factor XI deficiency bleed after trauma and others do not.4 , 5 , 7 No explanation for this enigma has been provided so far. Our data suggest that both the genotype and the site of surgery may affect bleeding manifestations in patients with the deficiency. It was observed that patients with genotype III/III had significantly fewer injury-related bleeding events than patients with genotype II/III or patients with genotype II/II. Conceivably, this relative advantage of patients with genotype III/III stemmed from their significantly higher factor XI:C levels (Table 1). Fibrinolytic activity at certain sites of surgical injury appears to be an important cause of bleeding in patients with impaired hemostasis.22 Thus, patients with severe hemophilia A can safely undergo oral surgery if their factor VIII:C level is raised to only 10 percent, provided they receive the antifibrinolytic agent tranexamic acid.23 Furthermore, patients taking oral anticoagulants do not need to cease treatment before oral surgery if they use mouthwashes with tranexamic acid after the procedure.24 Surgical sites particularly prone to bleeding due to local fibrinolysis are the urinary tract, because of the presence of urokinase in the urine,25 and nasal mucosa,26 buccal mucosa,27 and tissues exposed to saliva,28 because of the presence of tissue plasminogen activator. Consequently, we compared the frequency of bleeding complications in patients with severe factor XI deficiency after surgical procedures involving the urinary tract, nose, oral cavity, or tonsils with the frequency after other surgical procedures. This comparison showed that the proportion of patients (of all genotypes) who bled after procedures involving sites with local fibrinolytic activity was significantly higher than the proportion who bled after other surgical procedures (Table 2). Further analysis of the combined effect of the genotype and the site of surgery on bleeding was not possible because of the relatively small number of observations. Although it is conceivable that additional causes of injury-related bleeding in patients with severe factor XI deficiency will be found, the present findings imply that the use of antifibrinolytic agents may be an important adjunct to surgery at sites with local fibrinolysis.
Supported in part by a research grant (HL-16919) from the National Institutes of Health.
Source Information
From the Department of Biochemistry, University of Washington, Seattle (R.A., D.W.C., E.W.D.), and the Institute of Hematology, Ichilov Hospital, Tel Aviv, Israel (U.S.). Address reprint requests to Dr. Davie at the Department of Biochemistry, SJ-70, University of Washington, Seattle, WA 98195.
- References
References
1
Asakai
CrossRef | Web of Science | Medline2
Kato
CrossRef | Medline3
Rapaport
Web of Science | Medline4
Seligsohn
Web of Science | Medline5
Bolton-Maggs
CrossRef | Web of Science | Medline6
Saito
Medline7
Ragni
Web of Science | Medline8
Manhalter
Web of Science | Medline9
Harker LA. Hemostasis manual. 2nd ed. Philadelphia: F.A. Davis, 1974:28.
10
Asakai
CrossRef | Web of Science | Medline11
Siegel S. Nonparametric statistics for behavioural sciences. New York: McGraw-Hill, 1956:96–104.
12
Bell
CrossRef | Web of Science | Medline13
Saiki
CrossRef | Web of Science | Medline14
Bouma
Web of Science | Medline15
Laemmli
CrossRef | Web of Science | Medline16
Towbin
CrossRef | Web of Science | Medline17
Goodman RM. A perspective on genetic disease among the Jewish people. In: Goodman RM, Motulsky AG, eds. Genetic diseases among Ashkenazi Jews. New York: Raven Press, 1979:1–17.
18
Mandle
CrossRef | Web of Science | Medline19
Thompson
CrossRef | Web of Science | Medline20
Baglia
Web of Science | Medline21
Page 22
Walsh
CrossRef | Web of Science | Medline23
Sindet-Pedersen
CrossRef | Web of Science | Medline24
Sindet-Pedersen
Full Text | Web of Science | Medline25
Stump
Web of Science | Medline26
Rasmussen
CrossRef | Medline27
Birn
Medline28
Sindet-Pedersen
CrossRef | Web of Science | Medline
- Citing Articles (109)
Citing Articles
1
P. Gueguen, A. Chauvin, S. Quémener-Redon, B. Pan-Petesch, C. Ferec, J.-F. Abgrall, C. Le Maréchal. (2012) Revisiting the molecular epidemiology of factor XI deficiency: Nine new mutations and an original large 4qTer deletion in western Brittany (France). Thrombosis and Haemostasis 107:1, 44-50
CrossRef2
Aaron L. Fogelson, Yasmeen H. Hussain, Karin Leiderman. (2012) Blood Clot Formation under Flow: The Importance of Factor XI Depends Strongly on Platelet Count. Biophysical Journal 102:1, 10-18
CrossRef3
Rong He, Dong Chen, Shilin He. (2011) Factor XI: Hemostasis, Thrombosis, and Antithrombosis. Thrombosis Research
CrossRef4
Paul Guéguen, Hubert Galinat, Marie-Thérèse Blouch, Françoise Bridey, Jérôme Duchemin, Grégoire Le Gal, Jean-François Abgrall, Brigitte Pan-Petesch. (2011) Biological determinants of bleeding in patients with heterozygous factor XI deficiency. British Journal of Haematologyno-no
CrossRef5
Claudia Chi, Rezan A. Kadir. (2011) Inherited bleeding disorders in pregnancy. Best Practice & Research Clinical Obstetrics & Gynaecology
CrossRef6
Antonio Girolami, Pamela Scarparo, Emanuela Bonamigo, Liliana Santarossa, Andrea Cristiani, Stefano Moro, Anna Maria Lombardi. (2011) A cluster of factor XI-deficient patients due to a new mutation (Ile 436 Lys) in northeastern Italy*. European Journal of Haematologyno-no
CrossRef7
S. H. Choi, S. A. Smith, J. H. Morrissey. (2011) Polyphosphate is a cofactor for the activation of factor XI by thrombin. Blood
CrossRef8
Rita Santoro, Simona Prejanò, Piergiorgio Iannaccaro. (2011) Factor XI deficiency. Blood Coagulation & Fibrinolysis 22:5, 431-435
CrossRef9
F. BENLAKHAL, T. MURA, J.-F. SCHVED, M. GIANSILY-BLAIZOT, . (2011) A retrospective analysis of 157 surgical procedures performed without replacement therapy in 83 unrelated factor VII-deficient patients. Journal of Thrombosis and Haemostasis 9:6, 1149-1156
CrossRef10
L. DAI, S. RANGARAJAN, M. MITCHELL. (2011) Three dominant-negative mutations in factor XI-deficient patients. Haemophiliano-no
CrossRef11
Fania Szlam, Gautam Sreeram, Cristina Solomon, Jerrold H. Levy, Ross J. Molinaro, Kenichi A. Tanaka. (2011) Elevated factor VIII enhances thrombin generation in the presence of factor VIII-deficiency, factor XI-deficiency or fondaparinux. Thrombosis Research 127:2, 135-140
CrossRef12
J. J. van Veen, D. R. Spahn, M. Makris. (2011) Routine preoperative coagulation tests: an outdated practice?. British Journal of Anaesthesia 106:1, 1-3
CrossRef13
Jong Ho Lee, Hee Soon Cho, Myung Soo Hyun, Hwa-Young Kim, Hee-Jin Kim. (2011) A Novel Missense Mutation Asp506Gly in Exon 13 of the F11 Gene in an Asymptomatic Korean Woman with Mild Factor XI Deficiency. The Korean Journal of Laboratory Medicine 31:4, 290
CrossRef14
NS Key, JC Boles. 2011. Inherited disorders of coagulation. , 547-564.
CrossRef15
Stephen Hanessian, Andreas Larsson, Tomas Fex, Wolfgang Knecht, Niklas Blomberg. (2010) Design and synthesis of macrocyclic indoles targeting blood coagulation cascade Factor XIa. Bioorganic & Medicinal Chemistry Letters 20:23, 6925-6928
CrossRef16
H. Zhang, E. C. Lowenberg, J. R. Crosby, A. R. MacLeod, C. Zhao, D. Gao, C. Black, A. S. Revenko, J. C. M. Meijers, E. S. Stroes, M. Levi, B. P. Monia. (2010) Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk. Blood 116:22, 4684-4692
CrossRef17
E. C. LÖWENBERG, J. C. M. MEIJERS, B. P. MONIA, M. LEVI. (2010) Coagulation factor XI as a novel target for antithrombotic treatment. Journal of Thrombosis and Haemostasis 8:11, 2349-2357
CrossRef18
Flora Peyvandi, Marzia Menegatti. 2010. Rare Bleeding Disorders. , 813-838.
CrossRef19
L. RUGERI, F. QUÉLIN, B. CHATARD, P. DE MAZANCOURT, C. NEGRIER, Y. DARGAUD. (2010) Thrombin generation in patients with factor XI deficiency and clinical bleeding risk. Haemophilia 16:5, 771-777
CrossRef20
Uri Seligsohn, Paula H. B. Bolton-Maggs. 2010. Factor XI Deficiency. , 355-361.
CrossRef21
J. Emsley, P. A. McEwan, D. Gailani. (2010) Structure and function of factor XI. Blood 115:13, 2569-2577
CrossRef22
Ayala Maayan-Metzger, Lea Leibovitch, Irit Schushan-Eisen, Tzipora Strauss, Gili Kenet, Jacob Kuint. (2010) Predictors for neonatal thrombocytopenia in infants of thrombocytopenic mothers during pregnancy. Pediatric Blood & Cancern/a-n/a
CrossRef23
Ido Didi Fabian, Dan Sachs, Joseph Moisseiev, Amir Alhalel, Aharon Grinbaum, Uri Seligsohn, Ophira Salomon. (2009) Cataract Extraction Without Prophylactic Treatment in Patients With Severe Factor XI Deficiency. American Journal of Ophthalmology 148:6, 920-924.e1
CrossRef24
G. KENET, A. LUBETSKY, J. LUBOSHITZ, B. RAVID, I. TAMARIN, D. VARON, U. MARTINOWITZ. (2009) Lower doses of rFVIIa therapy are safe and effective for surgical interventions in patients with severe FXI deficiency and inhibitors. Haemophilia 15:5, 1065-1073
CrossRef25
U. SELIGSOHN. (2009) Factor XI deficiency in humans. Journal of Thrombosis and Haemostasis 7, 84-87
CrossRef26
David Gailani, Thomas Renné, Andras Gruber. 2009. Contact-Activation Pathways as Targets for New Anticoagulants. , 377-398.
CrossRef27
Amarjeet Singh, Miriam J. Harnett, Jean M. Connors, William R. Camann. (2009) Factor XI Deficiency and Obstetrical Anesthesia. Anesthesia & Analgesia 108:6, 1882-1885
CrossRef28
Ioannis Vasileiadis, Mahmoud El-Ali, Serafim Nanas, Spyros Kolias, Panayotis Zacharatos, Vassiliki Christopoulou-Cokkinou, Anastasia Kotanidou. (2009) First diagnosis of factor XI deficiency in a patient with subarachnoid haemorrhage. Blood Coagulation & Fibrinolysis 20:4, 309-313
CrossRef29
Mehran Karimi, Hamta Jafari, Saba Lahsaeizadeh, Abdolreza Afrasiabi, Ahmad Akbari, Javad Dehbozorgian, Rezvan Ardeshiri, Ilaria Guella, Rosanna Asselta, Flora Peyvandi. (2009) Factor XI deficiency in Southern Iran: identification of a novel missense mutation. Annals of Hematology 88:4, 359-363
CrossRef30
E. I. Tucker, U. M. Marzec, T. C. White, S. Hurst, S. Rugonyi, O. J. T. McCarty, D. Gailani, A. Gruber, S. R. Hanson. (2009) Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI. Blood 113:4, 936-944
CrossRef31
Yee Suk Kim, Eun Yong Chung, Jun Rho Yoon, In Soo Han, Ah Reum Park, Tae Kwan Kim, Chul Woo Lee. (2009) Anesthetic experience of a patient with hereditary factor XI deficiency (Hemophilia C) - A case report -. Korean Journal of Anesthesiology 56:6, 706
CrossRef32
Muhammad Fatum, Cuneyt Ozcan, Alex Simon, Aby Lewin, Neri Laufer. (2008) The safety of ultrasound-guided oocyte pick-up in IVF patients with haemostatic disorders. European Journal of Obstetrics & Gynecology and Reproductive Biology 137:2, 259-261
CrossRef33
K. GOMEZ, P. BOLTON-MAGGS. (2008) Factor XI deficiency. Haemophilia 0:0, 080227233758934-???
CrossRef34
E. ASATIANI, C. M. KESSLER, . (2007) Multiple congenital coagulopathies co-expressed with Von Willebrand’s disease: the experience of Hemophilia Region III Treatment Centers over 25 years and review of the literature. Haemophilia 13:6, 685-696
CrossRef35
Nobutsune Ishikawa, Satoshi Okada, Takashi Sato, Shin??ichiro Yasunaga, Motoaki Ohtsubo, Yoshihiro Takihara, Masao Kobayashi. (2007) A novel mutation (Gln433Glu) in exon 12 combined with the G insertion in exon 13 causes severe factor XI deficiency in Japanese patients. Blood Coagulation & Fibrinolysis 18:5, 519-523
CrossRef36
Georgios Mavromatidis, Konstantinos Dinas, Dimitrios Delkos, Fotios Goutzioulis, Christos Vosnakis, Emmanouel Hatzipantelis, Vassilia Garipidou, David Rousso. (2007) Uneventful cesarean delivery with administration of factor XI concentrate in a patient with severe factor XI deficiency. International Journal of Hematology 86:3, 222-224
CrossRef37
D. GAILANI, T. RENNÉ. (2007) The intrinsic pathway of coagulation: a target for treating thromboembolic disease?. Journal of Thrombosis and Haemostasis 5:6, 1106-1112
CrossRef38
D. Dirkmann, A. A. Hanke, K. Görlinger, J. Peters. (2007) Perioperative use of modified thrombelastography in factor XI deficiency: a helpful method to assess drug effects. Acta Anaesthesiologica Scandinavica 51:5, 640-643
CrossRef39
Iris Schrijver, Maigi Külm, Phyllis I. Gardner, Eugene P. Pergament, Morris B. Fiddler. (2007) Comprehensive Arrayed Primer Extension Array for the Detection of 59 Sequence Variants in 15 Conditions Prevalent Among the (Ashkenazi) Jewish Population. The Journal of Molecular Diagnostics 9:2, 228-236
CrossRef40
D. GAILANI, A. SCHMIDT, M.-F. SUN, P. H. BOLTON-MAGGS, S. P. BAJAJ. (2007) A cross-reactive material positive variant of coagulation factor XI (FXI P520L ) with a catalytic defect. Journal of Thrombosis and Haemostasis 5:4, 781-787
CrossRef41
Paul W. Riley, Hong Cheng, Dharmaraj Samuel, Heinrich Roder, Peter N. Walsh. (2007) Dimer Dissociation and Unfolding Mechanism of Coagulation Factor XI Apple 4 Domain: Spectroscopic and Mutational Analysis. Journal of Molecular Biology 367:2, 558-573
CrossRef42
Claudia Chi, Rezan A Kadir. (2007) Management of women with inherited bleeding disorders in pregnancy. The Obstetrician & Gynaecologist 9:1, 27-33
CrossRef43
Harold R. Roberts, Miguel A. Escobar. 2007. Less Common Congenital Disorders of Hemostasis. , 61-79.
CrossRef44
R. A. KADIR, C. E. C. KINGMAN, C. CHI, N. M. O'CONNELL, A. RIDDELL, C. A. LEE, D. L. ECONOMIDES. (2006) Screening for factor XI deficiency amongst pregnant women of Ashkenazi Jewish origin. Haemophilia 12:6, 625-628
CrossRef45
X. WANG, P. L. SMITH, M-Y. HSU, D. GAILANI, W. A. SCHUMACHER, M. L. OGLETREE, D. A. SEIFFERT. (2006) Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis in mice. Journal of Thrombosis and Haemostasis 4:9, 1982-1988
CrossRef46
O. SALOMON, D. M. STEINBERG, U. SELIGSHON. (2006) Variable bleeding manifestations characterize different types of surgery in patients with severe factor XI deficiency enabling parsimonious use of replacement therapy. Haemophilia 12:5, 490-493
CrossRef47
F. PEYVANDI, R. J. KAUFMAN, U. SELIGSOHN, O. SALOMON, P. H. B. BOLTON-MAGGS, M. SPREAFICO, M. MENEGATTI, R. PALLA, S. SIBONI, P. M. MANNUCCI. (2006) Rare bleeding disorders. Haemophilia 12:s3, 137-142
CrossRef48
Kate Khair, Ri Liesner. (2006) Bruising and bleeding in infants and children - a practical approach. British Journal of Haematology 133:3, 221-231
CrossRef49
Astrid Dossenbach-Glaninger, Pierre Hopmeier. (2006) Coagulation factor XI gene analysis in three factor XI deficient Austrian patients. European Journal of Haematology 76:4, 317-321
CrossRef50
B. N. BOUMA, P. A. K. VON DEM BORNE, J. C. M. MEIJERS. (2006) Discovery of thrombin activatable fibrinolysis inhibitor (TAFI). Journal of Thrombosis and Haemostasis 4:1, 257-258
CrossRef51
Ophira Salomon, Ariella Zivelin, Tami Livnat, Uri Seligsohn. (2006) Inhibitors to Factor XI in Patients With Severe Factor XI Deficiency. Seminars in Hematology 43, S10-S12
CrossRef52
Rebecca E. Saunders, Niamh M. O'Connell, Christine A. Lee, David J. Perry, Stephen J. Perkins. (2005) Factor XI deficiency database: an interactive web database of mutations, phenotypes, and structural analysis tools. Human Mutation 26:3, 192-198
CrossRef53
KENNETH M. HARGREAVES, ASMA KHAN. (2005) Surgical preparation: anesthesia & hemostasis. Endodontic Topics 11:1, 32-55
CrossRef54
Astrid Dossenbach-Glaninger, Pierre Hopmeier. (2005) Coagulation factor XI: a database of mutations and polymorphisms associated with factor XI deficiency. Blood Coagulation & Fibrinolysis 16:4, 231-238
CrossRef55
G. JAYANDHARAN, R. V. SHAJI, S. C. NAIR, M. CHANDY, A. SRIVASTAVA. (2005) Novel missense mutations in two patients with factor XI deficiency (Val271Leu and Tyr351Ser) and one patient with combined factor XI and factor IX deficiency (Phe349Val). Journal of Thrombosis and Haemostasis 3:4, 808-811
CrossRef56
X. WANG, Q. CHENG, L. XU, G. Z. FEUERSTEIN, M-Y. HSU, P. L. SMITH, D. A. SEIFFERT, W. A. SCHUMACHER, M. L. OGLETREE, D. GAILANI. (2005) Effects of factor IX or factor XI deficiency on ferric chloride-induced carotid artery occlusion in mice. Journal of Thrombosis and Haemostasis 3:4, 695-702
CrossRef57
Alexandra Bezak, Radosław Kaczanowski, Astrid Dossenbach-Glaninger, Krzysztof Kucharczyk, Werner Lubitz, Pierre Hopmeier. (2005) Detection of single nucleotide polymorphisms in coagulation factor XI deficient patients by multitemperature single-strand conformation polymorphism analysis. Journal of Clinical Laboratory Analysis 19:6, 233-240
CrossRef58
Kazuo Fujikawa. (2005) Historical perspective of factor XI. Thrombosis Research 115:6, 441-450
CrossRef59
Ophira Salomon, David M Steinberg, Ilia Tamarin, Ariella Zivelin, Uri Seligsohn. (2005) Plasma replacement therapy during labor is not mandatory for women with severe factor XI deficiency. Blood Coagulation & Fibrinolysis 16:1, 37-41
CrossRef60
N. M. O'CONNELL, R. E. SAUNDERS, C. A. LEE, D. J. PERRY, S. J. PERKINS. (2005) Structural interpretation of 42 mutations causing factor XI deficiency using homology modeling. Journal of Thrombosis and Haemostasis 3:1, 127-138
CrossRef61
L. DAI, M. MITCHELL, G. SAVIDGE, A. ALHAQ. (2004) The profibrinolytic effect of plasma thrombomodulin in factor XI deficiency and its implications in hemostasis. Journal of Thrombosis and Haemostasis 2:12, 2200-2204
CrossRef62
O. Salomon, U. Seligsohn. (2004) New observations on factor XI deficiency. Haemophilia 10:s4, 184-187
CrossRef63
A. Podmore, M. Smith, G. Savidge, A. Alhaq. (2004) Real-Time quantitative PCR analysis of factor XI mRNA variants in human platelets. Journal of Thrombosis and Haemostasis 2:10, 1713-1719
CrossRef64
D. Gailani, A. Zivelin, D. Sinha, P. N. Walsh. (2004) Do platelets synthesize factor XI?. Journal of Thrombosis and Haemostasis 2:10, 1709-1712
CrossRef65
P. H. B. Bolton-Maggs, D. J. Perry, E. A. Chalmers, L. A. Parapia, J. T. Wilde, M. D. Williams, P. W. Collins, S. Kitchen, G. Dolan, A. D. Mumford. (2004) The rare coagulation disorders - review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia 10:5, 593-628
CrossRef66
Victor E. A. Gerdes, Roderik A. Kraaijenhagen, Esther W. M. Vogels, Hugo Ten Cate, Pieter H. Reitsma. (2004) Factor XI gene analysis in thrombophilia and factor XI deficiency. Journal of Thrombosis and Haemostasis 2:6, 1015-1017
CrossRef67
Letian Dai, Michael Mitchell, Philip Carson, Desmond Creagh, Jacky Cutler, Geoffrey Savidge, Anwar Alhaq. (2004) Severe factor XI deficiency caused by compound heterozygosity. British Journal of Haematology 125:6, 817-818
CrossRef68
P. H. B. Bolton-Maggs, H. Peretz, R. Butler, R. Mountford, S. Keeney, L. Zacharski, A. Zivelin, U. Seligsohn. (2004) A common ancestral mutation (C128X) occurring in 11 non-Jewish families from the UK with factor XI deficiency. Journal of Thrombosis and Haemostasis 2:6, 918-924
CrossRef69
Niamh M O’Connell. (2004) Factor XI deficiency. Seminars in Hematology 41, 76-81
CrossRef70
Bonno N Bouma, Joost C.M Meijers. (2004) New insights into factors affecting clot stability: a role for thrombin activatable fibrinolysis inhibitor (TAFI; plasma procarboxypeptidase B, plasma procarboxypeptidase U, procarboxypeptidase R). Seminars in Hematology 41, 13-19
CrossRef71
F. Quelin, M. Trossaert, M. Sigaud, P. D. E. Mazancourt, E. Fressinaud. (2004) Molecular basis of severe factor XI deficiency in seven families from the west of France. Seven novel mutations, including an ancient Q88X mutation. Journal of Thrombosis and Haemostasis 2:1, 71-76
CrossRef72
Q. Cheng, M.-F. Sun, D. V. Kravtsov, L, A. Aktimur, D. Gailani. (2003) Factor XI apple domains and protein dimerization. Journal of Thrombosis and Haemostasis 1:11, 2340-2347
CrossRef73
P. N. Walsh. (2003) Roles of factor XI, platelets and tissue factor-initiated blood coagulation. Journal of Thrombosis and Haemostasis 1:10, 2081-2086
CrossRef74
S. Butenas, J. D. Dee, K. G. Mann. (2003) The function of factor XI in tissue factor-initiated thrombin generation. Journal of Thrombosis and Haemostasis 1:10, 2103-2111
CrossRef75
Akiko Tsukahara, Takayuki Yamada, Akira Takagi, Takashi Murate, Tadashi Matsushita, Hidehiko Saito, Tetsuhito Kojima. (2003) Compound heterozygosity for two novel mutations in a severe factor XI deficiency. American Journal of Hematology 73:4, 279-284
CrossRef76
B. N. Bouma, J.C. M. Meijers. (2003) Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U). Journal of Thrombosis and Haemostasis 1:7, 1566-1574
CrossRef77
Niamh M. O'Connell. (2003) Factor XI deficiency - from molecular genetics to clinical management. Blood Coagulation & Fibrinolysis 14:SUPPLEMENT 1, S59-S64
CrossRef78
L NORRIS. (2003) Blood coagulation. Best Practice & Research Clinical Obstetrics & Gynaecology 17:3, 369-383
CrossRef79
F.R. Rosendaal. (2003) Clotting and myocardial infarction: a cycle of insights. Journal of Thrombosis and Haemostasis 1:4, 640-642
CrossRef80
O. Salomon, D. M. Steinberg, R. Dardik, N. Rosenberg, A. Zivelin, I. Tamarin, B. Ravid, S. Berliner, U. Seligsohn. (2003) Inherited factor XI deficiency confers no protection against acute myocardial infarction. Journal of Thrombosis and Haemostasis 1:4, 658-661
CrossRef81
Bonno N. Bouma, Laurent O. Mosnier. (2003) Thrombin Activatable Fibrinolysis Inhibitor (TAFI) at the Interface between Coagulation and Fibrinolysis. Pathophysiology of Haemostasis and Thrombosis 33:5-6, 375-381
CrossRef82
F. Peyvandi, S. Duga, S. Akhavan, P. M. Mannucci. (2002) Rare coagulation deficiencies. Haemophilia 8:3, 308-321
CrossRef83
P. LAWLER, B. WHITE, S. PYE, C. HERMANS, A. RIDDELL, C. COSTELLO, S. BROWN, C. A. LEE. (2002) Successful use of recombinant factor VIIa in a patient with inhibitor secondary to severe factor XI deficiency. Haemophilia 8:2, 145-148
CrossRef84
Frank A. Baglia, Peter N. Walsh. 2002. Factor XI. .
CrossRef85
F. Peyvandi, R. Asselta, P.M. Mannucci. (2001) AUTOSOMAL RECESSIVE DEFICIENCIES OF COAGULATION FACTORS. Reviews in Clinical and Experimental Hematology 5:4, 369-388
CrossRef86
Astrid Dossenbach-Glaninger, Walter Krugluger, Karl Schrattbauer, Sabine Eder, Pierre Hopmeier. (2001) Severe factor XI deficiency caused by compound heterozygosity for the type III mutation and a novel insertion in exon 9 (codons 324/325 +G). British Journal of Haematology 114:4, 875-877
CrossRef87
Bonno N. Bouma, Pauline F. Marx, Laurent O. Mosnier, Joost C.M. Meijers. (2001) Thrombin-Activatable Fibrinolysis Inhibitor (TAFI, Plasma Procarboxypeptidase B, Procarboxypeptidase R, Procarboxypeptidase U). Thrombosis Research 101:5, 329-354
CrossRef88
J. di Paola, D. Nugent, G. Young. (2001) Current therapy for rare factor deficiencies. Haemophilia 7:s1, 16-22
CrossRef89
Takashi Tarumi, Danko Martincic, James A. Whitlock, Jonathan H. Addy, Scott M. Williams, David Gailani. (2000) Conserved Worldwide Linkage Disequilibrium in the Human Factor XI Gene. Genomics 70:2, 269-272
CrossRef90
Rebecca A. Shirk, Barbara A. Konkle, Peter N. Walsh. (2000) Nonsense mutation in exon V of the factor XI gene does not abolish platelet factor XI expression. British Journal of Haematology 111:1, 91-95
CrossRef91
Bonno N. Bouma, Joost C.M. Meijers. (2000) Role of blood coagulation factor XI in downregulation of fibrinolysis. Current Opinion in Hematology 7:5, 266-272
CrossRef92
Bolton-Maggs. (2000) Factor XI deficiency and its management. Haemophilia 6:s1, 100-109
CrossRef93
J. Teruya, M. Styler. (2000) Management of factor XI inhibitor for cardiac intervention: successful treatment with immunosuppressive therapy and plasma exchange. Haemophilia 6:3, 158-161
CrossRef94
Eriko Sato, Norihiko Kawamata, Atsushi Kato, Kazuo Oshimi. (2000) A novel mutation that leads to a congenital factor XI deficiency in a Japanese family. American Journal of Hematology 63:4, 165-169
CrossRef95
Meijers, Joost C.M., Tekelenburg, Winnie L.H., Bouma, Bonno N., Bertina, Rogier M., Rosendaal, Frits R., . (2000) High Levels of Coagulation Factor XI as a Risk Factor for Venous Thrombosis. New England Journal of Medicine 342:10, 696-701
Full Text96
Joël Zlotogora, Gideon Bach, Arnold Munnich. (2000) Molecular Basis of Mendelian Disorders among Jews. Molecular Genetics and Metabolism 69:3, 169-180
CrossRef97
Michael Mitchell, Jacky Cutler, Simon Thompson, Gary Moore, Elaine Jenkins ap Rees, Mark Smith, Geoffrey Savidge, Anwar Alhaq. (1999) Heterozygous factor XI deficiency associated with three novel mutations. British Journal of Haematology 107:4, 763-765
CrossRef98
Bauduer, Dupreuilh, Ducout, Marti. (1999) Factor XI deficiency in the French Basque Country. Haemophilia 5:3, 187-190
CrossRef99
Anwar Alhaq, Michael Mitchell, Meera Sethi, Salman Rahman, Geraldine Flynn, Peter Boulton, Gianfranco Caeno, Mark Smith, Geoffrey Savidge. (1999) Identification of a novel mutation in a non-Jewish factor XI deficient kindred. British Journal of Haematology 104:1, 44-49
CrossRef100
R.A. Kadir, D.L. Economides, C.A. Lee. (1999) Factor XI deficiency in women. American Journal of Hematology 60:1, 48-54
CrossRef101
K Sankaranarayanan. (1998) Ionizing radiation and genetic risks. Mutation Research/Reviews in Mutation Research 411:2, 129-178
CrossRef102
F Christiaens. (1998) Anaesthetic management of a parturient with severe congenital factor XI deficiency undergoing caesarean section for triplet pregnancy. International Journal of Obstetric Anesthesia 7:1, 50-53
CrossRef103
J. K. SMITH. (1996) Factor XI deficiency and its management. Haemophilia 2:3, 128-136
CrossRef104
PAULA BOLTON-MAGGS M. (1995) Factor XI deficiency: a review. Haemophilia 1:4, 217-221
CrossRef105
YASUFUMI IMANAKA, KALPANA LAL, TAKUYA NISHIMURA, PAULA H. B. BOLTON-MAGGS, EDWARD G. D. TITDDENHAM, JOHN H. MCVEY. (1995) Identification of two novel mutations in non-Jewish factor XI deficiency. British Journal of Haematology 90:4, 916-920
CrossRef106
P.H.B. Bolton-Maggs, F.G.H. Hill. (1995) The rarer inherited coagulation disorders: A review. Blood Reviews 9:2, 65-76
CrossRef107
Lori Luchtman-Jones, George J. Broze. (1995) The Current Status of Coagulation. Annals of Medicine 27:1, 47-52
CrossRef108
Robert W. Colman, A. Koneti Rao, Ronald N. Rubin, Peter N. Walsh. (1994) Factor XI deficiency and hemostasis. American Journal of Hematology 45:1, 73-78
CrossRef109
Steven S. Ginsberg, Lionel P. Clyne, Peter McPhedran, Thomas P. Duffy, T. Hanson†. (1993) Successful childbirth by a patient with congenital factor XI deficiency and an acquired inhibitor. British Journal of Haematology 84:1, 172-174
CrossRef
