Laboratory Studies

Activated partial thromboplastin time (aPTT) should be measured. In patients with severe factor XI (FXI) deficiency, the aPTT value will be more than two standard deviations above the normal mean; in heterozygotes, the aPTT may be slightly prolonged APTT or within the normal range.^[11]

An FXI assay may help confirm the diagnosis, although levels can be in the normal range.^[11]Homozygotes and compound heterozygotes will have an FXI level of less than 15%. The expected FXI level in heterozygotes is 25-70%.

A mixing study using normal pooled plasma may help identify a factor deficiency. If the sample is incubated and, subsequently, the aPTT is prolonged, then the presence of an inhibitor needs to be considered. Based on the data regarding high risk of inhibitor development in patients who have severe (< 1%) FXI deficiency, checking an inhibitor titer before proceeding with surgery is recommended.

Factor assays for the intrinsic coagulation system should be performed with at least three dilutions.

In a patient who is newly diagnosed and without previous bleeding history or family history (neither is uncommon in a patient with FXI deficiency), care must be taken by the coagulation laboratory to separate out a nonspecific inhibitor or lupus anticoagulant versus a true FXI deficiency.

Researchers are exploring the use of novel laboratory tests, such as thrombin generation assays and clot stability assays, to predict bleeding risk in patients with FXI deficiency.^[1] For example, Gidley et al reported that combining the apTT with the rate of clot formation and area under the curve in fibrinolysis assays identifies most FXI-deficient patients with a bleeding tendency.^[17]

Treatment & Management

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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].
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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].
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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].
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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.

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