Factor XI deficiency and its management

Abstract

Factor XI deficiency has a more variable bleeding tendency than haemophilia A or B. Individuals with severe deficiency have only a mild bleeding tendency, which is typically provoked by surgery, but the risk of bleeding is not restricted to individuals with severe deficiency. The bleeding tendency varies between individuals with similar factor XI levels, and sometimes the bleeding tendency of an individual may vary. The reasons for this are not fully understood, although in cases of severe deficiency there is some correlation between phenotype and genotype. Factor XI is activated by thrombin. The role of factor XI in physiological processes has become clearer since this fact was discovered, and the discovery has contributed to a revised model of blood coagulation. Factor XI deficiency occurs in all racial groups, but is particularly common in Ashkenazi Jews. The factor XI gene is 23 kilobases long. Two mutations are responsible for most factor XI deficiency in the Ashkenazi population, but a number of other mutations have now been reported in other racial groups. Individuals with factor XI deficiency may need specific therapy for surgery, accidents, and dental extractions. Several therapies are available which include fresh frozen plasma, factor XI concentrates, fibrin glue, antifibrinolytic drugs, and desmopressin. Each has advantages and risks to be considered. Factor XI concentrate may be indicated for procedures with a significant risk of bleeding especially in younger patients with severe deficiency, but its use in older patients has been associated with thrombotic phenomena. If fresh frozen plasma is to be used it is preferable to obtain one of the virally inactivated products. Fibrin glue is a useful treatment which deserves further study.

Factor XI–dependence of surface- and tissue factor–initiated thrombus propagation in primates

“…FXI, unlike coagulation factors of the extrinsic and common pathways, is not essential for hemostasis. 7 However, plasma FXI activity is required to occlusion following transvascular FeCl 3 -induced arterial injury and thrombosis in mice as well as the early postnatal mortality observed in protein C-deficient mice. 8,9 Moreover, FXI is an independent risk factor for thrombosis in humans.…”

Platelets and Thrombin Generation

“…Interestingly, factor XI deficiency results in a bleeding disorder that has significant variability between patients and is significantly milder than bleeding in patients with hemophilia A or B lacking factors VIII or IX, respectively. [17][18][19] It has long been established that coagulation reactions do not occur physiologically in solution but are localized to a surface. 6,20 -22 The critical advantage to evolving such a mechanism is that the reactions are confined to a specific site of injury rather than being completely disseminated.…”

“…114 Of particular interest is the variability seen in patients with factor XI deficiency. 19 Some patients with modest levels of factor XI antigen have severe bleeding symptoms, 17 whereas other patients with no detectable antigen lack significant bleeding symptoms. 18 Studies looking at the contribution of individual differences in platelet procoagulant function have at least 3 difficulties.…”

Factor XI in haemostasis and thrombosis: Past, present and future

“…Hence, major FXI deficiencyconfers amarkedlyhigherrisk of bleeding thanm inor deficiency. Patients with am inor deficiencyw ho have ableeding historyshould be tested for an additional hemostatic disorder.G uidelines for therapyi nF XI-deficient patients can be foundelsewhere (14,33).…”