eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders
Factor XI Deficiency: Treatment & Medication
Updated: Aug 6, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Patients with FXI deficiency do not need treatment or prophylaxis for routine functions or activities. They do need treatment for dental extractions and surgery. Expectant treatment of a pregnant woman is controversial if a cesarean delivery is not planned. Treatment of FXI deficiency is determined by the intervention planned.
- Fresh frozen plasma has been the most available source of FXI. The recovery of FXI function from plasma is excellent, and the half-life is 40-80 hours.
- Dental procedures have been performed safely with the use of factor replacement. Administration of antifibrinolytics alone was attempted when patients with FXI deficiency were recognized to be more likely to bleed in areas of high fibrinolysis. Patients since have been treated successfully with the use of tranexamic acid alone in preparation for dental extraction. The treatment is begun before the procedure and continued for an additional week.
- Invasive surgical procedures often require fresh frozen plasma replacement. This should be continued for 7-14 days after surgery. Remember that the half-life of FXI is approximately 52 hours (2 d).
- Pregnant women will need fresh frozen plasma if cesarean delivery is planned. Peripartum treatment of women with FXI deficiency is controversial. One group treats patients to maintain FXI levels above 50% during labor and then continues treatment for 3-4 days after vaginal delivery and 7 days after cesarean delivery. This is recommended because of the high incidence of postpartum hemorrhage. The recommendation to treat expectantly must be understood in the context of the known variability of bleeding manifestations based on patient history and FXI level, as well as the unpredictable risk of exposure to blood-borne pathogens with the use of fresh frozen plasma.
- The use of desmopressin, a vasopressin analog, used for patients with factor VIII deficiency, von Willebrand disease, and platelet function abnormalities, has been tried in a handful of patients with FXI deficiency. In the patients reported, 3 of whom had baseline FXI levels ranging from 34-45%, factor level increased from 12% to 23%. In one patient with severe ( <1%) FXI deficiency, the level did not increase. The 4 patients presented in these published reports had no surgical bleeding. The true benefit of this treatment is unclear, and it is not recommended for major surgical procedures.
- Antifibrinolytic therapy has been used in the treatment of women with FXI deficiency and menorrhagia.
- Treatment of patients with acquired antibodies to FXI has not been standardized because of the infrequency of this occurrence. Successful treatment has been reported during invasive procedures with the use of plasma, prothrombin complex concentrates, and recombinant activated factor VII. Reports also exist of patients with inhibitors who have no spontaneous bleeds.
- Unless needed for another medical indication, aspirin products should be avoided by patients with FXI deficiency.
Surgical Care
Immunization by hepatitis A virus and hepatitis B virus vaccines is recommended prior to planned surgery and plasma product replacement.
Consultations
Consultation with a hematologist is recommended.
Diet
No dietary restrictions are indicated.
Activity
No restrictions on activity are necessary.
Medication
Blood products
To achieve a FXI level of 50%, a patient needs to have half of their plasma volume replaced.
Directed-donor fresh frozen plasma can be arranged for elective procedures, but a large volume of plasma will need to be stored to transfuse for the required 7-14 days after surgery. One study has demonstrated that solvent detergent fresh frozen plasma has a half-life of 45 hours, while a second study has shown that FXI is decreased in the product.
Fresh frozen plasma (FFP)
Plasma is the fluid compartment of blood containing the soluble clotting factors.
Adult
20 mL/kg IV; continued dosing is required after surgery
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
A - Safe in pregnancy
Precautions
Viral contamination and infection are possible but unlikely due to prescreening; ineffective in patients with FXI inhibitors; may induce anamnestic response
Aminocaproic acid (Amicar)
Inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. Main problem is that the thrombi that form during treatment are not lysed, and effectiveness is uncertain.
Adult
0.1 g/kg IV before surgery, followed by 0.1 g/kg PO q6h for 10 d; not to exceed 24 g/24 h
4-5 g IV, followed by 1 g q1h for up to 8 h
Menorrhagia: 2 g PO q6h may be used
Pediatric
5-30 g/d PO/IV in divided doses q3-6h; not to exceed 18 g/m2/24h
Coadministration with estrogens may cause increase in clotting factors, leading to hypercoagulable state
Documented hypersensitivity; evidence of active intravascular clotting process; because aminocaproic acid can be fatal in patients with DIC, differentiating between hyperfibrinolysis and DIC is important
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Do not administer unless diagnosis of hyperfibrinolysis has been established definitely; caution in cardiac, hepatic, or renal disease
Tranexamic acid (Cyklokapron)
Alternative to aminocaproic acid. Inhibits fibrinolysis by displacing plasminogen from fibrin. (Not available in United States)
Adult
10 mg/kg IV, followed by 25 mg/kg PO tid/qid for 2-8 d
25 mg/kg PO tid/qid beginning 1 d before surgery
Menorrhagia: 0.5 g PO 6 times per day or 1 g
PO q6h or 4 g PO qd for 3 d
Dental extractions: 1 g PO qid 12 h before oral surgery; continue for 1 wk
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in renal impairment
More on Factor XI Deficiency |
| Overview: Factor XI Deficiency |
| Differential Diagnoses & Workup: Factor XI Deficiency |
 Treatment & Medication: Factor XI Deficiency |
| Follow-up: Factor XI Deficiency |
| Multimedia: Factor XI Deficiency |
| References |
| « Previous Page | Next Page » |
References
Asakai R, Chung DW, Davie EW, Seligsohn U. Factor XI deficiency in Ashkenazi Jews in Israel. N Engl J Med. Jul 18 1991;325(3):153-8. [Medline].
Azzi A, De Santis R, Morfini M, et al. TT virus contaminates first-generation recombinant factor VIII concentrates. Blood. Oct 15 2001;98(8):2571-3. [Medline].
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. [Medline].
Berliner S, Horowitz I, Martinowitz U, et al. Dental surgery in patients with severe factor XI deficiency without plasma replacement. Blood Coagul Fibrinolysis. Aug 1992;3(4):465-8. [Medline].
Bolton-Maggs PH. Factor XI deficiency and its management. World Federation of Hemophilia Monograph;1999:16.
Bolton-Maggs PH. Factor XI deficiency and its management. Haemophilia. Jul 2000;6 Suppl 1:100-9. [Medline].
Bolton-Maggs PH, Patterson DA, Wensley RT, Tuddenham EG. Definition of the bleeding tendency in factor XI-deficient kindreds--a clinical and laboratory study. Thromb Haemost. Feb 1995;73(2):194-202. [Medline].
Bolton-Maggs PH, Peretz H, Butler R, et al. A common ancestral mutation (C128X) occurring in 11 non-Jewish families from the UK with factor XI deficiency. J Thromb Haemost. Jun 2004;2(6):918-24.
Bonnar J, Sheppard BL. Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid. BMJ. Sep 7 1996;313(7057):579-82. [Medline].
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. Jul 1996;94(1):168-70. [Medline].
Clarkson K, Rosenfeld B, Fair J, et al. Factor XI deficiency acquired by liver transplantation. Ann Intern Med. Dec 1 1991;115(11):877-9. [Medline].
Coukos G, Rubin SC. Gene therapy for ovarian cancer. Oncology (Huntingt). Sep 2001;15(9):1197-204, 1207; discussion 1207-8. [Medline].
Di Bisceglie AM. SEN and sensibility: interactions between newly discovered and other hepatitis viruses?. Lancet. Dec 8 2001;358(9297):1925-6. [Medline].
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. May 7 1987;316(19):1217-8. [Medline].
Hancock JF, Wieland K, Pugh RE, et al. A molecular genetic study of factor XI deficiency. Blood. May 1 1991;77(9):1942-8. [Medline].
Hedner U, Ginsburg D, Lusher JM, High KA. Congenital Hemorrhagic Disorders: New Insights into the Pathophysiology and Treatment of Hemophilia. Hematology (Am Soc Hematol Educ Program). 2000;241-265. [Medline].
Kadir RA, Economides DL, Lee CA. Factor XI deficiency in women. Am J Hematol. Jan 1999;60(1):48-54. [Medline].
Kravtsov DV, Monahan PE, Gailani D, et al. A classification system for cross-reactive material-negative factor XI deficiency. Blood. Jun 15 2005;105(12):4671-3.
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. Nov 1 1998;92(9):3309-17. [Medline].
MediView Express. Recombinant therapy enhances safety andquality of life for hemophilia patients. Paper presented at: 53rd Annual Meeting of the National Hemophilia Foundation. November 16, 2001;Nashville, Tennessee.
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. Oct 1 1997;90(7):2654-9. [Medline].
Rigas B, Hasan I, Rehman R, et al. Effect on treatment outcome of coinfection with SEN viruses in patients with hepatitis C. Lancet. Dec 8 2001;358(9297):1961-2. [Medline].
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.
Salomon O, Seligsohn U. New observations on factor XI deficiency. Haemophilia. Oct 2004;10 Suppl 4:184-7.
Salomon O, Zivelin A, Livnat T, et al. Prevalence, causes, and characterization of factor XI inhibitors in patients with inherited factor XI deficiency. Blood. Jun 15 2003;101(12):4783-8. [Medline].
Saunders RE, O''Connell NM, Lee CA, et al. Factor XI deficiency database: an interactive web database of mutations, phenotypes, and structural analysis tools. Hum Mutat. Sep 2005;26(3):192-8.
Seligsohn U. The activated partial thromboplastin time and factor XI deficiency. Ann Intern Med. Nov 1986;105(5):805. [Medline].
Seligsohn U, White GC. Inherited deficiencies of coagulation factors II, V, VII, XI, and XIII and the combined deficiencies of factors V and VIII and of the vitamin K-dependent factors. In: Beutler E, Lichtman MA,Coller BS, et al, eds. Williams Hematology. McGraw-Hill;2001:1617-38.
Siegel JE, Kouides PA. Menorrhagia from a haematologist''s point of view. Part II: management. Haemophilia. May 2002;8(3):339-47. [Medline].
Sun MF, Baglia FA, Ho D, et al. Defective binding of factor XI-N248 to activated human platelets. Blood. Jul 1 2001;98(1):125-9. [Medline].
Walsh P. Factor XI. In: Colman RW, Hirsh J, Marder VJ, et al, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 4th ed. Lippincott Williams & Wilkins;1987.
Zivelin A, Bauduer F, Ducout L, et al. Factor XI deficiency in French Basques is caused predominantly by an ancestral Cys38Arg mutation in the factor XI gene. Blood. Apr 1 2002;99(7):2448-54. [Medline].
Zivelin A, Ogawa T, Bulvik S, et al. Severe factor XI deficiency caused by a Gly555 to Glu mutation (factor XI-Glu555): a cross-reactive material positive variant defective in factor IX activation. J Thromb Haemost. Oct 2004;2(10):1782-9.
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. Aug 2009;102(2):287-301. [Medline].
Franchini M, Manzato F, Salvagno GL, Montagnana M, Lippi G. The use of desmopressin in congenital factor XI deficiency: a systematic review. Ann Hematol. Jul 17 2009;epub ahead of print. [Medline].
Kravtsov DV, Matafonov A, Tucker EI, et al. Factor XI contributes to thrombin generation in the absence of factor XII. Blood. Jul 9 2009;114(2):452-8. [Medline].
Seligsohn U. Factor XI deficiency in humans. J Thromb Haemost. Jul 2009;7 suppl 1:84-7. [Medline].
Further Reading
Keywords
factor XI deficiency, FXI deficiency, hemophilia C, plasma thromboplastin antecedent deficiency, Rosenthal's syndrome, Rosenthal syndrome, PTA deficiency, bleeding disorder
