History

Bleeding in persons with factor XI (FXI) deficiency occurs with dental extractions, trauma, or surgery. The FXI level does not correlate with or act as a predictor of bleeding risk.^[16]Within individual patients and their family, highly variable and unpredictable bleeding patterns occur. Bleeding can be immediate or delayed.

Considerations in the history are as follows:

Circumcision may be the first manifestation of this bleeding disorder, but a negative history does not exclude FXI deficiency
Bleeding with dental extractions is a common manifestation
Menorrhagia has been reported in as many as 59% of women with FXI deficiency; in one study of women with menorrhagia, 4% were found to have FXI deficiency. ^[2]
An inconsistent history of bleeding in the same patient may be observed with FXI deficiency.
FXI deficiency in an asymptomatic patient may be identified only by a prolonged activated partial thromboplastin time (aPTT) on routine preoperative testing.
Family history may reflect an autosomal dominant or recessive pattern of inheritance.

Physical Examination

Physical manifestations of FXI deficiency are rare. Bruising and petechiae usually are not observed with this coagulation disorder. No chronic joint abnormalities occur. After a surgical procedure, if a patient has remained undiagnosed and untreated, a significant hematoma may occur in the area of surgery.

Differential Diagnoses

Wheeler AP, Gailani D. Why factor XI deficiency is a clinical concern. Expert Rev Hematol. 2016 Jul. 9 (7):629-37. [QxMD MEDLINE Link]. [Full Text].
Kadir RA, Economides DL, Lee CA. Factor XI deficiency in women. Am J Hematol. 1999 Jan. 60(1):48-54. [QxMD MEDLINE Link]. [Full Text].
Rosenthal RL, Dreskin OH, Rosenthal N. New hemophilia-like disease caused by deficiency of a third plasma thromboplastin factor. Proc Soc Exp Biol Med. 1953. 82:171-4.
Choi SH, Smith SA, Morrissey JH. Polyphosphate is a cofactor for the activation of factor XI by thrombin. Blood. 2011 Dec 22. 118(26):6963-70. [QxMD MEDLINE Link].
Rugeri L, Quélin F, Chatard B, De Mazancourt P, Negrier C, Dargaud Y. Thrombin generation in patients with factor XI deficiency and clinical bleeding risk. Haemophilia. 2010 Sep 1. 16(5):771-7. [QxMD MEDLINE Link].
Dzik WH, Arkin CF, Jenkins RL. Transfer of congenital factor XI deficiency from a donor to a recipient by liver transplantation. N Engl J Med. 1987 May 7. 316(19):1217-8. [QxMD MEDLINE Link].
Clarkson K, Rosenfeld B, Fair J, et al. Factor XI deficiency acquired by liver transplantation. Ann Intern Med. 1991 Dec 1. 115(11):877-9. [QxMD MEDLINE Link].
Kravtsov DV, Monahan PE, Gailani D. A classification system for cross-reactive material-negative factor XI deficiency. Blood. 2005 Jun 15. 105 (12):4671-3. [QxMD MEDLINE Link]. [Full Text].
Asakai R, Chung DW, Davie EW, Seligsohn U. Factor XI deficiency in Ashkenazi Jews in Israel. N Engl J Med. 1991 Jul 18. 325(3):153-8. [QxMD MEDLINE Link].
Peretz H, Mulai A, Usher S, et al. 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. 1997 Oct 1. 90(7):2654-9. [QxMD MEDLINE Link].
Seligsohn U. Factor XI deficiency in humans. J Thromb Haemost. 2009 Jul. 7 suppl 1:84-7. [QxMD MEDLINE Link].
Martincic D, Zimmerman SA, Ware RE, et al. Identification of mutations and polymorphisms in the factor XI genes of an African American family by dideoxyfingerprinting. Blood. 1998 Nov 1. 92(9):3309-17. [QxMD MEDLINE Link].
Saunders RE, Shiltagh N, Gomez K, et al. Structural analysis of eight novel and 112 previously reported missense mutations in the interactive FXI mutation database reveals new insight on FXI deficiency. Thromb Haemost. 2009 Aug. 102(2):287-301. [QxMD MEDLINE Link].
Qu Y, Nie X, Yang Z, Yin H, Pang Y, Dong P, et al. The prevalence of hemophilia in mainland China: a systematic review and meta-analysis. Southeast Asian J Trop Med Public Health. 2014 Mar. 45(2):455-66. [QxMD MEDLINE Link].
Knol HM, Mulder AB, Bogchelman DH, Kluin-Nelemans HC, van der Zee AG, Meijer K. The prevalence of underlying bleeding disorders in patients with heavy menstrual bleeding with and without gynecologic abnormalities. Am J Obstet Gynecol. 2013 Sep. 209(3):202.e1-7. [QxMD MEDLINE Link].
Guéguen P, Galinat H, Blouch MT, Bridey F, Duchemin J, Le Gal G, et al. Biological determinants of bleeding in patients with heterozygous factor XI deficiency. Br J Haematol. 2012 Jan. 156(2):245-51. [QxMD MEDLINE Link].
Gidley GN, Holle LA, Burthem J, Bolton-Maggs PHB, Lin FC, Wolberg AS. Abnormal plasma clot formation and fibrinolysis reveal bleeding tendency in patients with partial factor XI deficiency. Blood Adv. 2018 May 22. 2 (10):1076-1088. [QxMD MEDLINE Link]. [Full Text].
Gerber GF, Klute KA, Chapin J, Bussel J, DeSancho MT. Peri- and Postpartum Management of Patients With Factor XI Deficiency. Clin Appl Thromb Hemost. 2019 Jan-Dec. 25:1076029619880262. [QxMD MEDLINE Link].
Berliner S, Horowitz I, Martinowitz U, et al. Dental surgery in patients with severe factor XI deficiency without plasma replacement. Blood Coagul Fibrinolysis. 1992 Aug. 3(4):465-8. [QxMD MEDLINE Link].
Salomon O, Steinberg DM, Seligshon U. Variable bleeding manifestations characterize different types of surgery in patients with severe factor XI deficiency enabling parsimonious use of replacement therapy. Haemophilia. 2006 Sep. 12 (5):490-3. [QxMD MEDLINE Link].
Stoeckle JH, Bogue T, Zwicker JI. Postpartum haemorrhage in women with mild factor XI deficiency. Haemophilia. 2020 Jul. 26 (4):663-666. [QxMD MEDLINE Link].
Bauduer F, Bendriss P, Freyburger G, et al. Use of desmopressin for prophylaxis of surgical bleeding in factor XI- deficient patients. Acta Haematol. 1998. 99(1):52-3. [QxMD MEDLINE Link].
Castaman G, Ruggeri M, Rodeghiero F. Clinical usefulness of desmopressin for prevention of surgical bleeding in patients with symptomatic heterozygous factor XI deficiency. Br J Haematol. 1996 Jul. 94(1):168-70. [QxMD MEDLINE Link].
Franchini M, Manzato F, Salvagno GL, Montagnana M, Lippi G. The use of desmopressin in congenital factor XI deficiency: a systematic review. Ann Hematol. 2009 Jul 17. epub ahead of print. [QxMD MEDLINE Link].
Salomon O, Budnik I, Avishai E, Tamarin I, Bashari D, Dardik R, et al. Single Low Dose of rFVIIa Combined with Antifibrinolytic Agent is a Simple and Safe Treatment for Factor XI-Deficient Patients undergoing Surgery. Thromb Haemost. 2019 Sep 7. [QxMD MEDLINE Link].
Minami H, Nogami K, Yada K, Ogiwara K, Furukawa S, Soeda T, et al. Emicizumab, the bispecific antibody to factors IX/IXa and X/Xa, potentiates coagulation function in factor XI-deficient plasma in vitro. J Thromb Haemost. 2019 Jan. 17 (1):126-137. [QxMD MEDLINE Link].
Bravo-Pérez C, Serna MJ, Esteban J, Fernandez-Mellid E, Fontanes-Trabazo E, Lorenzo A, et al. Anticoagulant therapy in patients with congenital FXI deficiency. Blood Adv. 2021 Oct 26. 5 (20):4083-4086. [QxMD MEDLINE Link].

Media Gallery

Factor XI deficiency. Diagram from the traditional cascade-waterfall model of coagulation shows the place of factor XI in the intrinsic pathway, which leads to the common pathway.

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Author

Jamie E Siegel, MD Director, Cardeza Foundation Hemophilia Treatment Center, Thomas Jefferson University

Jamie E Siegel, MD is a member of the following medical societies: American College of Physicians, American Society for Clinical Pathology, American Society of Hematology, International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MD, FRCPC, DTM&H Professor Emeritus of Internal Medicine and Hematology/Oncology, Emeritus Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MD, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Srikanth Nagalla, MD, MS, FACP Chief of Benign Hematology, Miami Cancer Institute, Baptist Health South Florida; Clinical Professor of Medicine, Florida International University, Herbert Wertheim College of Medicine

Srikanth Nagalla, MD, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Alexion; Alnylam; Kedrion; Sanofi; Dova; Apellis; Pharmacosmos<br/>Serve(d) as a speaker or a member of a speakers bureau for: Sobi; Sanofi; Rigel.

Additional Contributors

Paul Schick, MD † Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Factor XI Deficiency Clinical Presentation

History

Physical Examination

References

Tables

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