FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 325:153-158 July 18, 1991 Number 3 Next

	Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

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.

Source Information

Department of Biochemistry, University of Washington, Seattle 98195.

This article has been cited by other articles:

• Salomon, O., Steinberg, D. M., Koren-Morag, N., Tanne, D., Seligsohn, U. (2008). Reduced incidence of ischemic stroke in patients with severe factor XI deficiency. Blood 111: 4113-4117 [Abstract] [Full Text]  
• Smith, S. B., Verhamme, I. M., Sun, M.-f., Bock, P. E., Gailani, D. (2008). Characterization of Novel Forms of Coagulation Factor XIa: INDEPENDENCE OF FACTOR XIa SUBUNITS IN FACTOR IX ACTIVATION. J. Biol. Chem. 283: 6696-6705 [Abstract] [Full Text]  
• Zucker, M., Zivelin, A., Teitel, J., Seligsohn, U. (2008). Induction of an inhibitor antibody to factor XI in a patient with severe inherited factor XI deficiency by Rh immune globulin. Blood 111: 1306-1308 [Abstract] [Full Text]  
• Siao, D., Seetapah, A., Ryman, A., Guerin, V., Mesli, A., Maurette, P. (2008). Optimal Management of an Aneurysmal Subarachnoid Hemorrhage in a Patient With Known Factor XI Deficiency: A Case Report. CLIN APPL THROMB HEMOST 14: 108-111 [Abstract]  
• Gailani, D., Renne, T. (2007). Intrinsic Pathway of Coagulation and Arterial Thrombosis. Arterioscler. Thromb. Vasc. Bio. 27: 2507-2513 [Abstract] [Full Text]  
• Zucker, M., Zivelin, A., Landau, M., Salomon, O., Kenet, G., Bauduer, F., Samama, M., Conard, J., Denninger, M.-H., Hani, A.-S., Berruyer, M., Feinstein, D., Seligsohn, U. (2007). Characterization of seven novel mutations causing factor XI deficiency. haematol 92: 1375-1380 [Abstract] [Full Text]  
• Schrijver, I., Kulm, M., Gardner, P. I., Pergament, E. P., Fiddler, M. B. (2007). Comprehensive Arrayed Primer Extension Array for the Detection of 59 Sequence Variants in 15 Conditions Prevalent Among the (Ashkenazi) Jewish Population. J. Mol. Diagn. 9: 228-236 [Abstract] [Full Text]  
• Chi, C., Kadir, R. A (2007). Management of women with inherited bleeding disorders in pregnancy. The Obstetrician and Gynaecologist 9: 27-33 [Abstract] [Full Text]  
• Kleinschnitz, C., Stoll, G., Bendszus, M., Schuh, K., Pauer, H.-U., Burfeind, P., Renne, C., Gailani, D., Nieswandt, B., Renne, T. (2006). Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J. Exp. Med. 203: 513-518 [Abstract] [Full Text]  
• Salomon, O., Steinberg, D. M., Seligsohn, U. (2005). A Relatively Low Frequency of Bleeding in Patients with Severe Factor XI Deficiency Who Undergo Surgery Involving Tissues with Low Fibrinolytic Activity Supports on Demand Rather Than Prophylactic Use of Plasma.. ASH ANNUAL MEETING ABSTRACTS 106: 4036-4036 [Abstract]  
• Cheng, Q., Zhao, Y., Lawson, W. E., Polosukhin, V. V., Johnson, J. E., Blackwell, T. S., Gailani, D. (2005). The effects of intrinsic pathway protease deficiencies on plasminogen-deficient mice. Blood 106: 3055-3057 [Abstract] [Full Text]  
• Ogawa, T., Verhamme, I. M., Sun, M.-F., Bock, P. E., Gailani, D. (2005). Exosite-mediated Substrate Recognition of Factor IX by Factor XIa: THE FACTOR XIa HEAVY CHAIN IS REQUIRED FOR INITIAL RECOGNITION OF FACTOR IX. J. Biol. Chem. 280: 23523-23530 [Abstract] [Full Text]  
• Kravtsov, D. V., Monahan, P. E., Gailani, D. (2005). A classification system for cross-reactive material-negative factor XI deficiency. Blood 105: 4671-4673 [Abstract] [Full Text]  
• Mannucci, P. M., Duga, S., Peyvandi, F. (2004). Recessively inherited coagulation disorders. Blood 104: 1243-1252 [Abstract] [Full Text]  
• Kravtsov, D. V., Wu, W., Meijers, J. C. M., Sun, M.-F., Blinder, M. A., Dang, T. P., Wang, H., Gailani, D. (2004). Dominant factor XI deficiency caused by mutations in the factor XI catalytic domain. Blood 104: 128-134 [Abstract] [Full Text]  
• Salomon, O., Zivelin, A., Livnat, T., Dardik, R., Loewenthal, R., Avishai, O., Steinberg, D. M., Rosove, M. H., O'Connell, N., Lee, C. A., Seligsohn, U. (2003). Prevalence, causes, and characterization of factor XI inhibitors in patients with inherited factor XI deficiency. Blood 101: 4783-4788 [Abstract] [Full Text]  
• Troxel, M. T., Brooks, M. B., Esterline, M. L. (2002). Congenital Factor XI Deficiency in a Domestic Shorthair Cat. Journal of the American Animal Hospital Association 38: 549-553 [Abstract] [Full Text]  
• Tarumi, T., Kravtsov, D. V., Zhao, M., Williams, S. M., Gailani, D. (2002). Cloning and Characterization of the Human Factor XI Gene Promoter. TRANSCRIPTION FACTOR HEPATOCYTE NUCLEAR FACTOR 4alpha (HNF-4alpha ) IS REQUIRED FOR HEPATOCYTE-SPECIFIC EXPRESSION OF FACTOR XI. J. Biol. Chem. 277: 18510-18516 [Abstract] [Full Text]  
• Zivelin, A., Bauduer, F., Ducout, L., Peretz, H., Rosenberg, N., Yatuv, R., Seligsohn, U. (2002). Factor XI deficiency in French Basques is caused predominantly by an ancestral Cys38Arg mutation in the factor XI gene. Blood 99: 2448-2454 [Abstract] [Full Text]  
• Sun, M.-F., Baglia, F. A., Ho, D., Martincic, D., Ware, R. E., Walsh, P. N., Gailani, D. (2001). Defective binding of factor XI-N248 to activated human platelets. Blood 98: 125-129 [Abstract] [Full Text]  
• Meijers, J. C.M., Tekelenburg, W. L.H., Bouma, B. N., Bertina, R. M., Rosendaal, F. R. (2000). High Levels of Coagulation Factor XI as a Risk Factor for Venous Thrombosis. NEJM 342: 696-701 [Abstract] [Full Text]  
• Martincic, D., Kravtsov, V., Gailani, D. (1999). Factor XI Messenger RNA in Human Platelets. Blood 94: 3397-3404 [Abstract] [Full Text]  
• Martincic, D., Zimmerman, S. A., Ware, R. E., Sun, M.-F., Whitlock, J. A., Gailani, D. (1998). Identification of Mutations and Polymorphisms in the Factor XI Genes of an African American Family by Dideoxyfingerprinting. Blood 92: 3309-3317 [Abstract] [Full Text]  
• Hsu, T.-C., Shore, S. K., Seshsmma, T., Bagasra, O., Walsh, P. N. (1998). Molecular Cloning of Platelet Factor XI, an Alternative Splicing Product of the Plasma Factor XI Gene. J. Biol. Chem. 273: 13787-13793 [Abstract] [Full Text]  
• Peretz, H., Mulai, A., Usher, S., Zivelin, A., Segal, A., Weisman, Z., Mittelman, M., Lupo, H., Lanir, N., Brenner, B., Shpilberg, O., Seligsohn, U. (1997). The Two Common Mutations Causing Factor XI Deficiency in Jews Stem From Distinct Founders: One of Ancient Middle Eastern Origin and Another of More Recent European Origin. Blood 90: 2654-2659 [Abstract] [Full Text]  
• Brenner, B., Stemberg, T., Laor, A., Tavori, S., Tatarsky, I., Lanir, N. (1995). Von Willebrand Factor Antigen and Factor XI Activity Levels As Predictors of Bleeding Tendency in Israeli Patients with Von Willebrand's Disease. CLIN APPL THROMB HEMOST 1: 260-264 [Abstract]  
• Murakami, T., Komiyama, Y., Masuda, M., Karakawa, M., Iwasaka, T., Takahashi, H. (1995). Evaluation of Factor XIa–{alpha}1-Antitrypsin in Plasma, a Contact Phase–Activated Coagulation Factor–Inhibitor Complex, in Patients With Coronary Artery Disease. Arterioscler. Thromb. Vasc. Bio. 15: 1107-1113 [Abstract] [Full Text]