Approach Considerations
Patients with factor XI (FXI) deficiency do not need treatment or prophylaxis for routine functions or activities, but may need treatment for dental extractions, surgery, and childbirth. [11, 18] Treatment of FXI deficiency is determined by patient factors and clinical circumstances.
Fresh frozen plasma (FFP) 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. FXI concentrates are produced in the United Kingdom and France, but are not available in the United States. [11]
Dental extractions have been performed safely in severely FXI-deficient patients with the use of antifibrinolytic therapy alone. Tranexamic acid, 1 g four times daily, was started 12 hours before the procedure and continued for 7 days afterward. [19] Antifibrinolytic therapy has also been used in the treatment of women with FXI deficiency and menorrhagia. [2]
Invasive surgical procedures often require replacement therapy with FFP. This should be continued for 7-14 days after surgery. Bear in mind that the half-life of FXI is approximately 52 hours (2 d).
However, before starting FFP the surgeon needs to consider the risks, which include volume overload, transmission of infectious agents, thrombosis, allergic reactions, and development of inhibitors to FXI. In addition, even patients with severe FXI deficiency do not inevitably bleed with surgery, and bleeding most often occurs with procedures involving tissues that exhibit fibrinolytic activity, Consequently, Salomon et al suggest that surgeons may consider forgoing replacement therapy in procedures involving sites that do not have local fibrinolytic activity. [20]
Pregnant women will need FFP if cesarean delivery is planned. In a case-control study of 40 women with mild factor XI deficiency, the rate of postpartum hemorrhage was significantly higher among the 26 cesarean deliveries compared with 75 control cesarean deliveries in women with no known bleeding disorder (odds ratio [OR] 2.73, 95% CI 1.02-7.26). The women who experienced postpartum hemorrhage had either a positive bleeding history or another risk factor. There were no episodes of postpartum hemorrhage among the vaginal deliveries. [21]
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 FFP.
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. [22, 23, 24] In the patients reported, three 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 four 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.
Salomon et al reported success with a single, very low dose of recombinant factor VIIa (rFVIIa) along with tranexamic acid as prophylactic treatment for FXI-deficient patients undergoing surgery. In their study of 12 procedures in 10 patients, rFVIIa was given in a single dose of 10 to 15 μg/kg at the end of surgery; tranexamic acid, 4 g/day, was started 2 hours before surgery and continued for 3 to 5 days. [25]
Minami et al reported that emicizumab potentiates coagulation function in FXI-deficient plasma. These authors suggest that this agent might provide possibilities for clinical application in patients with FXI deficiency. [26] Emicizumab, the bispecific antibody to factors IX/IXa and X/Xa, is currently approved for routine prophylaxis in patients with hemophilia A.
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 FFP, prothrombin complex concentrates, and rFVIIa. 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.
Although FXI deficiency offers some antithrombotic protection, patients may still develop indications for anticoagulation therapy, such as atrial fibrillation. A retrospective review by Bravo-Perez et al of 15 patients with mild to moderate FXI deficiency who required anticoagulation therapy (principally for atrial fibrillation) recorded 2 mild bleeding episodes in 2 patients, and no major or fatal events. Although four of the patients were on direct oral anticoagulants by the end of the follow-up period, 14 started therapy with vitamin K antagonists (VKA), and VKA dosing and management were standard in those cases, unaltered by FXI deficiency. [27]
Immunization with hepatitis A virus and hepatitis B virus vaccines is recommended prior to planned surgery and plasma product replacement. Consultation with a hematologist is recommended.
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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.
